RU2012144751A - Гетероциклические соединения, эффективные для ингибирования киназы - Google Patents

Гетероциклические соединения, эффективные для ингибирования киназы Download PDF

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RU2012144751A
RU2012144751A RU2012144751/04A RU2012144751A RU2012144751A RU 2012144751 A RU2012144751 A RU 2012144751A RU 2012144751/04 A RU2012144751/04 A RU 2012144751/04A RU 2012144751 A RU2012144751 A RU 2012144751A RU 2012144751 A RU2012144751 A RU 2012144751A
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Ли Дэниел АРНОЛЬД
Эрик А. МЕРФИ
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Амитек Терапетикс Солюшинс, Инк.
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Abstract

1. Соединение формулы (I)или его N-оксид, N,N'-диоксид, N,N',N''-триоксид, или фармацевтически приемлемая соль:в которой:Q представляет собой O или S;W представляет собой C-Cарил или C-Cгетероарил, содержащий 1-3 гетероатома;каждый из Х и Y независимо отсутствует или представляет собой NH;каждый из Zи Zнезависимо выбран из группы, состоящей из CH, N, и NR, где Rпредставляет собой водород или низший алкил;Zпредставляет собой O, S, N, или NR, где Rпредставляет собой водород или низший алкил;Rпредставляет собой незамещенный или замещенный C-Cгетроарил, содержащий 1-3 гетероатома, или алкил, замещенный незамещенным или замещенным C-Cгетроарилом, содержащим 1-3 гетероатома;каждый из Rи Rнезависимо выбран из группы, состоящей из водорода, C-Cалкокси, необязательно замещенного C-Cаалкила, необязательно замещенного C-Cциклоалкила, необязательно замещенного C-Cгетероцикла, содержащего 1-3 гетероатома, необязательно замещенного C-Cарила, необязательно замещенного C-Cгетероарила, содержащего 1-3 гетероатома, CF, галогена, CN, CONHRи COR', где R' представляет собой водород или C-Cалкил; или, необязательно, Rи R, объединены вместе с образованием от пяти- до семичленного карбоцикла;Rнезависимо выбран из группы, состоящей из водорода, галогена, C-Cалкила, --OH, NO, -CN, C-Cалкокси, -NHSOR, -SONHR, -NHCOR, -NH, -NRR, -SR, -S(O)R, -S(O)R, -COR, -CONRR, где Rи Rнезависимо выбраны из группы, состоящей из водорода и необязательно замещенного C-Cалкила; p=0-4 и n равен 1 или 2.2. Соединение по п.1, в котором W представляет собой C-Cарил.3. Соединение по п.1, в котором Rпредставляет собой незамещенный или замещенный C-Cгетероарил, содержащий 1-3 гетероатома.4. Соединение по п.1, в котором Rпредставляет собой водород.5. Соединение по п.1, в котором

Claims (15)

1. Соединение формулы (I)
Figure 00000001
или его N-оксид, N,N'-диоксид, N,N',N''-триоксид, или фармацевтически приемлемая соль:
в которой:
Q представляет собой O или S;
W представляет собой C6-C12арил или C3-C12гетероарил, содержащий 1-3 гетероатома;
каждый из Х и Y независимо отсутствует или представляет собой NH;
каждый из Z1 и Z2 независимо выбран из группы, состоящей из CH, N, и NR5, где R5 представляет собой водород или низший алкил;
Z3 представляет собой O, S, N, или NR5, где R5 представляет собой водород или низший алкил;
R1 представляет собой незамещенный или замещенный C3-C12гетроарил, содержащий 1-3 гетероатома, или алкил, замещенный незамещенным или замещенным C3-C12гетроарилом, содержащим 1-3 гетероатома;
каждый из R2 и R3 независимо выбран из группы, состоящей из водорода, C1-C6алкокси, необязательно замещенного C1-C6аалкила, необязательно замещенного C3-C12циклоалкила, необязательно замещенного C3-C10гетероцикла, содержащего 1-3 гетероатома, необязательно замещенного C6-C12арила, необязательно замещенного C3-C12гетероарила, содержащего 1-3 гетероатома, CF3, галогена, CN, CONHR6 и CO2R', где R' представляет собой водород или C1-C6алкил; или, необязательно, R2 и R3, объединены вместе с образованием от пяти- до семичленного карбоцикла;
R4 независимо выбран из группы, состоящей из водорода, галогена, C1-C6алкила, --OH, NO2, -CN, C1-C6алкокси, -NHSO2R6, -SO2NHR6, -NHCOR6, -NH2, -NR6R7, -SR6, -S(O)R6, -S(O)2R6, -CO2R6, -CONR6R7, где R6 и R7 независимо выбраны из группы, состоящей из водорода и необязательно замещенного C1-C6алкила; p=0-4 и n равен 1 или 2.
2. Соединение по п.1, в котором W представляет собой C6-C12арил.
3. Соединение по п.1, в котором R1 представляет собой незамещенный или замещенный C3-C12гетероарил, содержащий 1-3 гетероатома.
4. Соединение по п.1, в котором R4 представляет собой водород.
5. Соединение по п.1, в котором каждый из R2 и R3 независимо выбран из группы, состоящей из C1-C6алкила, -CF3 и галогена, где p равен 0, или 1, или 2; или, необязательно, R2 и R3 объединены вместе с образованием от пяти- до семичленного карбоцикла.
6. Соединение по п.1, где соединение формулы (I) выбрано из группы, состоящей из:
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 00000031
,
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 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
, и  
Figure 00000075
.
7. Соединение по п.1 формулы (II)
Figure 00000076
или его N-оксид, N,N'-диоксид, N,N',N''-триоксид, или фармацевтически приемлемая соль:
в которой:
R8 и R9 независимо выбраны из группы, состоящей из водорода, галогена, необязательно замещенного C1-C6алкила, -CF3, -OH, необязательно замещенного C1-C6алкокси, -NR10R11, и -SOmR12, где R10 и R11 независимо выбраны из группы, состоящей из водорода, необязательно замещенного C1-C6алкила, -SO2R12, -S(O)R12, и -COR12, и R12 представляет собой необязательно замещенный алкил или необязательно замещенный C3-C12гетероарил, содержащий 1-3 гетероатома и m равен 0-2.
8. Соединение по п.7, в котором R8 и R9 независимо выбраны из группы, состоящей из необязательно замещенного C1-C6алкокси, -NR10R11, и -SOmR12 и m равен 0-2.
9. Соединение по п.8, в котором каждый из R2 и R3 независимо выбраны из группы, состоящей из C1-C6алкилв, -CF3, и галогена, где p равен 0, или 1, или 2; или, необязательно, R2 и R3 объединены вместе с образованием от пяти- до семичленного карбоцикла.
10. Соединение по п.9, где соединение формулы (II) выбрано из группы, состоящей из:
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 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
, и
Figure 00000146
.
11. Соединение по п.1, выбранное из группы, состоящей из:
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 00000191
,
Figure 00000192
,
Figure 00000193
,
Figure 00000194
,
Figure 00000195
,
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
, и
Figure 00000220
.
12. Соединение по п.1, выбранное из группы, состоящей из:
Figure 00000221
,
Figure 00000222
,
Figure 00000223
,
Figure 00000224
,
Figure 00000225
,
Figure 00000226
,
Figure 00000227
,
Figure 00000228
,
Figure 00000229
, и
Figure 00000230
.
13. Соединение формулы (V)
Figure 00000231
или его N-оксид, N,N'-диоксид, N,N',N''-триоксид, или фармацевтически приемлемая соль:
в которой:
R1 представляет собой незамещенный или замещенный C3-C12 гетероарил, содержащий 1-3 гетероатома, или алкил, замещенный незамещенным или замещенным C3-C12гетероарилом, содержащим 1-3 гетероатома;
R4 независимо выбран из группы, состоящей из водорода, галогена, C1-C6алкила, -OH, -NO2, -CN, C1-C6алкокси, -NHSO2R6, -SO2NHR6, -NHCOR6, -NH2, -NR6R7, -SR6, -S(O)R6, -S(O)2R6, -CO2R6, и -CONR6R7, где R6 и R7 независимо выбраны из группы, состоящей из водорода, и необязательно замещенного C1-C6алкила; n равен 1 или 2; и
R14 выбран из группы, состоящей из необязательно замещенного C1-C12алкила, необязательно замещенного C3-C12циклоалкила, необязательно замещенного C3-C10гетероцикла, содержащего 1-3 гетероатома, необязательно замещенного C6-C12арила, и необязательно замещенного C3-C12гетероарила, содержащего 1-3 гетероатома.
14. Фармацевтическая композиция, содержащая соединение по п.1 в фармацевтически приемлемом носителе.
15. Способ лечения рака, рестеноза, гиперплазии интимы, фиброзирующих заболеваний или расстройств, связанных с ангиогенезом, у пациента-человека, включающий введение соединения по п.1 пациенту, нуждающемуся в этом.
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Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI625121B (zh) 2009-07-13 2018-06-01 基利科學股份有限公司 調節細胞凋亡信號之激酶的抑制劑
JP2013518909A (ja) * 2010-02-08 2013-05-23 キナゲン，インク． アロステリックキナーゼ阻害が関係する治療方法および組成物
CA2794086A1 (en) * 2010-03-24 2011-09-29 Amitech Therapeutic Solutions, Inc. Heterocyclic compounds useful for kinase inhibition
MX2012015105A (es) 2010-07-02 2013-05-28 Gilead Sciences Inc Inhibidores de cinasa de regulacion mediante señal de apoptosis.
EP2651417B1 (en) 2010-12-16 2016-11-30 Calchan Limited Ask1 inhibiting pyrrolopyrimidine derivatives
WO2012088266A2 (en) 2010-12-22 2012-06-28 Incyte Corporation Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3
US9408885B2 (en) 2011-12-01 2016-08-09 Vib Vzw Combinations of therapeutic agents for treating melanoma
UY34573A (es) 2012-01-27 2013-06-28 Gilead Sciences Inc Inhibidor de la quinasa que regula la señal de la apoptosis
ME02651B (me) 2012-06-13 2017-06-20 Incyte Holdings Corp Substituisana triciklična jedinjenja kao inhibitori fgfr
US9388185B2 (en) 2012-08-10 2016-07-12 Incyte Holdings Corporation Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors
US9266892B2 (en) 2012-12-19 2016-02-23 Incyte Holdings Corporation Fused pyrazoles as FGFR inhibitors
CA2909207C (en) 2013-04-19 2021-11-02 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
EA201691788A1 (ru) * 2014-04-25 2017-03-31 Пфайзер Инк. Гетероароматические соединения и их применение в качестве допаминовых d1 лигандов
US9868744B2 (en) 2014-04-25 2018-01-16 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
CA2962572A1 (en) 2014-09-24 2016-03-31 Gilead Sciences, Inc. Methods of treating liver disease with a combination of an ask1 inhibitor and a fxr agonist
US10851105B2 (en) 2014-10-22 2020-12-01 Incyte Corporation Bicyclic heterocycles as FGFR4 inhibitors
EP3693366B8 (en) 2014-12-23 2023-08-09 Gilead Sciences, Inc. Processes for preparing ask1 inhibitors
MA41252A (fr) 2014-12-23 2017-10-31 Gilead Sciences Inc Formes solides d'un inhibiteur d'ask 1
CR20170390A (es) 2015-02-20 2017-10-23 Incyte Holdings Corp Heterociclos biciclicos como inhibidores de fgfr
MA41551A (fr) 2015-02-20 2017-12-26 Incyte Corp Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4
WO2016134294A1 (en) 2015-02-20 2016-08-25 Incyte Corporation Bicyclic heterocycles as fgfr4 inhibitors
EP3293177A4 (en) * 2015-04-07 2018-12-12 Guangdong Zhongsheng Pharmaceutical Co., Ltd Tyrosine kinase inhibitor and pharmaceutical composition comprising same
WO2018134254A1 (en) 2017-01-17 2018-07-26 Heparegenix Gmbh Protein kinase inhibitors for promoting liver regeneration or reducing or preventing hepatocyte death
US11471538B2 (en) 2017-02-10 2022-10-18 INSERM (Institut National de la Santéet de la Recherche Medicale) Methods and pharmaceutical compositions for the treatment of cancers associated with activation of the MAPK pathway
AR111960A1 (es) 2017-05-26 2019-09-04 Incyte Corp Formas cristalinas de un inhibidor de fgfr y procesos para su preparación
JP7416716B2 (ja) 2017-12-28 2024-01-17 トラクト ファーマシューティカルズ インコーポレイテッド 円柱上皮幹細胞のための幹細胞培養系およびそれに関連した使用法
CN108191781B (zh) * 2018-01-08 2020-01-21 浙江大学 取代三氮唑类衍生物及其在制备抗肿瘤转移药物中的应用
GB201801226D0 (en) * 2018-01-25 2018-03-14 Redx Pharma Plc Modulators of Rho-associated protein kinase
BR112020022373A2 (pt) 2018-05-04 2021-02-02 Incyte Corporation sais de um inibidor de fgfr
WO2019213544A2 (en) 2018-05-04 2019-11-07 Incyte Corporation Solid forms of an fgfr inhibitor and processes for preparing the same
CN108864060A (zh) * 2018-06-03 2018-11-23 刘思良 一种重氮类衍生物及其在癌症治疗中的应用
CN108610336A (zh) * 2018-06-03 2018-10-02 刘思良 一种重氮类衍生物及其在癌症治疗中的应用
CN108586439A (zh) * 2018-06-03 2018-09-28 刘思良 一种Raf激酶抑制剂及其在癌症治疗中的应用
WO2020185532A1 (en) 2019-03-08 2020-09-17 Incyte Corporation Methods of treating cancer with an fgfr inhibitor
MX2021009863A (es) 2019-03-21 2021-11-12 Onxeo Una molecula dbait en combinacion con inhibidor de quinasa para el tratamiento del cancer.
WO2020245208A1 (en) 2019-06-04 2020-12-10 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of cd9 as a biomarker and as a biotarget in glomerulonephritis or glomerulosclerosis
US11591329B2 (en) 2019-07-09 2023-02-28 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
JOP20220083A1 (ar) 2019-10-14 2023-01-30 Incyte Corp حلقات غير متجانسة ثنائية الحلقة كمثبطات لـ fgfr
US11566028B2 (en) 2019-10-16 2023-01-31 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
KR20220098759A (ko) 2019-11-08 2022-07-12 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) 키나제 억제제에 대해 내성을 획득한 암의 치료 방법
BR112022010664A2 (pt) 2019-12-04 2022-08-16 Incyte Corp Derivados de um inibidor de fgfr
JP2023505258A (ja) 2019-12-04 2023-02-08 インサイト・コーポレイション Ｆｇｆｒ阻害剤としての三環式複素環
WO2021146424A1 (en) 2020-01-15 2021-07-22 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
CN115916966A (zh) * 2020-01-30 2023-04-04 加利福尼亚大学董事会 Strad结合剂及其用途
TW202313611A (zh) 2021-06-09 2023-04-01 美商英塞特公司 作為ｆｇｆｒ抑制劑之三環雜環
WO2023222849A1 (en) * 2022-05-19 2023-11-23 Astrazeneca Ab Amino heteroaromatic compounds useful in the treatment of liver diseases

Family Cites Families (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3598123A (en) 1969-04-01 1971-08-10 Alza Corp Bandage for administering drugs
US3598122A (en) 1969-04-01 1971-08-10 Alza Corp Bandage for administering drugs
US3993073A (en) 1969-04-01 1976-11-23 Alza Corporation Novel drug delivery device
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
US3996934A (en) 1971-08-09 1976-12-14 Alza Corporation Medical bandage
US3742951A (en) 1971-08-09 1973-07-03 Alza Corp Bandage for controlled release of vasodilators
BE795384A (fr) 1972-02-14 1973-08-13 Ici Ltd Pansements
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
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
US4031893A (en) 1976-05-14 1977-06-28 Survival Technology, Inc. Hypodermic injection device having means for varying the medicament capacity thereof
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
US4291015A (en) 1979-08-14 1981-09-22 Key Pharmaceuticals, Inc. Polymeric diffusion matrix containing a vasodilator
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
US5312325A (en) 1987-05-28 1994-05-17 Drug Delivery Systems Inc Pulsating transdermal drug delivery system
US5633009A (en) 1990-11-28 1997-05-27 Sano Corporation Transdermal administration of azapirones
US5540664A (en) 1993-05-27 1996-07-30 Washington Biotech Corporation Reloadable automatic or manual emergency injection system
US5358489A (en) 1993-05-27 1994-10-25 Washington Biotech Corporation Reloadable automatic or manual emergency injection system
AU1994295A (en) 1994-05-16 1995-12-05 Washington Biotech Corporation Modular automatic or manual emergency medicine injection system
AU3087195A (en) 1994-08-02 1996-03-04 Nippon Soda Co., Ltd. Oxazole derivative, process for producing the same, and herbicide
US5665378A (en) 1994-09-30 1997-09-09 Davis; Roosevelt Transdermal therapeutic formulation
US6923983B2 (en) 1996-02-19 2005-08-02 Acrux Dds Pty Ltd Transdermal delivery of hormones
US6929801B2 (en) 1996-02-19 2005-08-16 Acrux Dds Pty Ltd Transdermal delivery of antiparkinson agents
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
US7544189B2 (en) 2000-10-10 2009-06-09 Meridian Medical Technologies, Inc. Needle and hub assembly for automatic injector
EP1446110A2 (en) * 2001-10-16 2004-08-18 Structural Bioinformatics Inc. Organosulfur inhibitors of tyrosine phosphatases
WO2004032882A2 (en) * 2002-10-10 2004-04-22 Smithkline Beecham Corporation Chemical compounds
CL2003002353A1 (es) * 2002-11-15 2005-02-04 Vertex Pharma Compuestos derivados de diaminotriazoles, inhibidores d ela proteina quinasa; composicion farmaceutica; procedimiento de preparacion; y su uso del compuesto en el tratamiento de enfermedades de desordenes alergicos, proliferacion, autoinmunes, condic
US20090048301A1 (en) * 2003-07-09 2009-02-19 Imclone Systems Incorporated Heterocyclic compounds and their use as anticancer agents
US7754747B2 (en) * 2004-08-23 2010-07-13 Wyeth Llc Oxazolo-naphthyl acids
CN101044136A (zh) 2004-08-23 2007-09-26 惠氏公司 作为pai－1抑制剂的吡咯基－萘基酸
MX2007002208A (es) * 2004-08-25 2007-05-08 Targegen Inc Compuestos hetrociclicos y metodos de uso.
CN101044125A (zh) * 2004-08-25 2007-09-26 塔尔基公司 杂环化合物和应用方法
EP1844035A1 (en) * 2005-02-01 2007-10-17 Wyeth Amino-pyridines as inhibitors of beta-secretase
JP5201817B2 (ja) * 2005-10-28 2013-06-05 大塚製薬株式会社 医薬組成物
US7868177B2 (en) * 2006-02-24 2011-01-11 Amgen Inc. Multi-cyclic compounds and method of use
US7932390B2 (en) * 2006-06-29 2011-04-26 Hoffman-La Roche Inc. Substituted thieno[3,2-C]pyridine carboxylic acid derivatives
CN101600712A (zh) 2007-01-29 2009-12-09 参天制药株式会社 具有血管新生抑制活性的新型噁二唑衍生物及噻二唑衍生物
JP5540227B2 (ja) 2009-02-04 2014-07-02 株式会社大塚製薬工場 フェニルイミダゾール化合物
JP2013518909A (ja) 2010-02-08 2013-05-23 キナゲン，インク． アロステリックキナーゼ阻害が関係する治療方法および組成物
CA2794086A1 (en) 2010-03-24 2011-09-29 Amitech Therapeutic Solutions, Inc. Heterocyclic compounds useful for kinase inhibition

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AU2011232372A1 (en) 2012-11-08
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