Derivatives of gefitinib
This invention relates to novel quinazoline derivatives, their derivatives, pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by inhibiting cell surface tyrosine receptor kinases.
1. A method of modulating the activity of an epidermal growth factor receptor tyrosine kinase in a cell comprising contacting the cell with a compound of Formula A
or a pharmaceutically acceptable salt thereof, wherein the compound is selected from any one of the compounds depicted in the following Table:
TABLE
Y 1 =
Y 3 =
Y 5 =
Y 7 =
Cmpd
Y 2
Y 4
Y 6
Y 8
R 1
R 2
R 3
101
D
D
D
D
CD 3
CD 2 CD 2 CD 2
F
102
H
H
H
H
CD 3
CD 2 CD 2 CD 2
F
104
H
H
H
H
CD 3
CH 2 CH 2 CH 2
F
108
D
D
D
D
CD 3
CD 2 CD 2 CD 2
H
109
H
H
H
H
CD 3
CD 2 CD 2 CD 2
H
110
D
D
D
D
CD 3
CH 2 CH 2 CH 2
H
111
H
H
H
H
CD 3
CH 2 CH 2 CH 2
H
112
D
D
D
D
CD 3
CD 2 CD 2 CD 2
H
113
H
H
H
H
CD 3
CD 2 CD 2 CD 2
H
114
D
D
D
D
CD 3
CH 2 CH 2 CH 2
H
115
D
D
D
D
CD 3
CD 2 CD 2 CD 2
OH
116
H
H
H
H
CD 3
CD 2 CD 2 CD 2
OH
117
D
D
D
D
CD 3
CH 2 CH 2 CH 2
OH
118
H
H
H
H
CD 3
CH 2 CH 2 CH 2
OH
119
D
D
D
D
CD 3
CD 2 CD 2 CD 2
OH
120
H
H
H
H
CD 3
CD 2 CD 2 CD 2
OH
121
D
D
D
D
CD 3
CH 2 CH 2 CH 2
OH
122
D
D
D
D
CD 3
CD 2 CD 2 CD 2
OCD 3
123
H
H
H
H
CD 3
CD 2 CD 2 CD 2
OCD 3
124
D
D
D
D
CD 3
CH 2 CH 2 CH 2
OCD 3
125
H
H
H
H
CD 3
CH 2 CH 2 CH 2
OCD 3
126
D
D
D
D
CD 3
CD 2 CD 2 CD 2
OCD 3
127
H
H
H
H
CD 3
CD 2 CD 2 CD 2
OCD 3
128
D
D
D
D
CD 3
CH 2 CH 2 CH 2
OCD 3
129
D
D
D
D
CD 3
CD 2 CD 2 CD 2
OCH 3
130
H
H
H
H
CD 3
CD 2 CD 2 CD 2
OCH 3
131
D
D
D
D
CD 3
CH 2 CH 2 CH 2
OCH 3
132
H
H
H
H
CD 3
CH 2 CH 2 CH 2
OCH 3
133
D
D
D
D
CD 3
CD 2 CD 2 CD 2
OCH 3
134
H
H
H
H
CD 3
CD 2 CD 2 CD 2
OCH 3
135
D
D
D
D
CD 3
CH 2 CH 2 CH 2
OCD 3
136
D
D
D
D
CD 3
CD 2 CD 2 CD 2
Cl
137
H
H
H
H
CD 3
CD 2 CD 2 CD 2
Cl
138
D
D
D
D
CD 3
CH 2 CH 2 CH 2
Cl
139
H
H
H
H
CD 3
CH 2 CH 2 CH 2
Cl
140
D
D
D
D
CD 3
CD 2 CD 2 CD 2
Cl
141
H
H
H
H
CD 3
CD 2 CD 2 CD 2
Cl
142
D
D
D
D
CD 3
CH 2 CH 2 CH 2
Cl
143
D
D
D
D
CD 3
CD 2 CD 2 CD 2
Br
144
H
H
H
H
CD 3
CD 2 CD 2 CD 2
Br
145
D
D
D
D
CD 3
CH 2 CH 2 CH 2
Br
146
H
H
H
H
CD 3
CH 2 CH 2 CH 2
Br
147
D
D
D
D
CD 3
CD 2 CD 2 CD 2
Br
148
H
H
H
H
CD 3
CD 2 CD 2 CD 2
Br
149
D
D
D
D
CD 3
CH 2 CH 2 CH 2
Br.