USRE47451EActiveUtilityPatentIndex 60
Thieno[3,2-D]pyrimidine derivatives having inhibitory activity for protein kinases
Est. expiryDec 30, 2031(~5.5 yrs left)· nominal 20-yr term from priority
Inventors:BAE IN HWANSON JUNG BEOMHAN SANG MIKWAK EUN JOOKIM HO SEOKSONG JI YOUNGBYUN EUN YOUNGJUN SEUNG AHAHN YOUNG GILSUH KWEE-HYUN
A61P 35/02A61P 37/00A61P 3/10A61P 43/00A61P 3/08A61P 35/00A61P 9/10A61P 37/06A61P 25/28A61P 29/00A61P 31/04A61P 27/02A61P 3/04A61P 19/02A61P 11/06A61P 17/06A61P 13/12C07D 495/04A61K 45/06A61K 31/519A61K 31/5377C07D 519/00A61K 2300/00
60
PatentIndex Score
1
Cited by
31
References
63
Claims
Abstract
Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1. A thieno[3,2-d]pyrimidine compound of formula (I) or a pharmaceutically acceptable salt thereof:
wherein,
A is hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C 6-10 aryl or, 5- to 10-membered heteroaryl,
2,3-dihydrobenzo[b][1,4]dioxin-6-yl, benzo[d][1,3]dioxol-5-yl, 5,6,7,8-tetrahydronaphthalen-2-yl, idolin-6-yl, 1,4-diethyl-1,2,3,4,-tetrahydroquinoxalin-6-yl;, 2-methyl-1,3-dioxoisoindolin-5-yl, or 5-oxo-5,6,7,-8-tetrahydronaphthalen-2-yl;
W is O, S, S(O), S(O) 2 , NH, —NHNH— or 3- to 6-membered heterocycloalkyl;
X and Y are each independently CH or N;
Z is hydrogen, C 1-3 alkyl or NR 3 R 4 , wherein said R 3 and R 4 are each independently hydrogen, C 1-6 alkyl or —(CH 2 )q-B—, B representing NR 5 R 6 , C 1-6 alkoxy, C 3-6 cycloalkyl or 3- to 6-membered heterocycloalkyl;
R 1 is hydrogen, halogen, C 1-3 alkyl or C 1-3 alkoxy, wherein said alkyl or alkoxy is unsubstituted or substituted with one or more halogen atoms;
R 2 is hydrogen, halogen, ═O, —CF 3 , —NO 2 , —OH, —CN, C 1-6 alkoxy, C 1-6 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, —NR 7 R 8 , —NHSO 2 R 9 , —SO 2 R 10 , —C(O)R 11 , —NHC(O)R 12 , —NHC(O)OR 13 , —S(O)R 14 , C 3-6 cycloalkyl, 5- to 10-membered heterocycloalkyl 3- to 6-membered heterocycloalkyl, C 6-10 aryl, C 6-10 aryloxy, 5- to 10-membered heteroaryl or 3- to 6-membered heteroaryloxy 5- to 10-membered heteroaryloxy, wherein said R 2 is connected to A by —(CH 2 )p- or substituted with C 1-4 alkyl, C 2-4 alkynyl, C 1-4 alkylcarbonyl or one or more halogen atoms;
R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 are each independently hydrogen, —NH 2 , C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl or 3- to 6-membered heterocycloalkyl, said alkyl, alkoxy, cycloalkyl or heterocycloalkyl being unsubstituted or substituted with one or more halogen atoms;
q is an integer ranging from 0 to 3;
p is an integer ranging from 0 to 3;
m is an integer ranging from 0 to 5; and
n is an integer ranging from 0 to 2; and
when A is hydrogen, m is 0.
2. The thieno[3,2-d]pyrimidine compound or its pharmaceutically acceptable salt of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is C 6-10 aryl or 5- to 10-membered heteroaryl.
3. The thieno[3,2-d]pyrimidine compound or its pharmaceutically acceptable salt of claim 1 , or a pharmaceutically acceptable salt thereof, wherein W is NH.
4. The thieno[3,2-d]pyrimidine compound or its pharmaceutically acceptable salt of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is NR 3 R 4 .
5. The thieno[3,2-d]pyrimidine compound or its pharmaceutically acceptable salt of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is CH and Y is N.
6. The A thieno[3,2-d]pyrimidine compound or its pharmaceutically acceptable salt of claim 1 , which is selected from the group consisting of:
1) 4-amino-N-(1-((4-chlorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
2) 4-amino-N-(6-methyl-1-((3-(trifluoromethyl)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
3) N-(1-((4-chlorophenyl)amino)-6-methylisoquinolin-5-yl)-4-(cyclopropylamino)thieno[3,2-d]pyrimidine-7-carboxamide;
4) 4-(cyclopropylamino)-N-(6-methyl-1-((3-(trifluoromethyl)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
5) 4-amino-N-(6-methyl-1-((3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
6) 4-(cyclopropylamino)-N-(6-methyl-1-((3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
7) 4-amino-N-(1-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
8) 4-(cyclopropylamino)-N-(1-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
9) N-(1-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)amino)-6-methylisoquinolin-5-yl)-4-(methylamino)thieno[3,2-d]pyrimidine-7-carboxamide;
10) 4-amino-N-(1-((4-(4-ethylpiperazin-1-yl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
11) 4-amino-N-(1-((4-((4-ethylpiperazin-1-yl)methyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
12) 4-amino-N-(6-methyl-1-((3-(trifluoromethyl)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
13) 4-amino-N-(1-((4-chloro-3-(trifluoromethyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
14) 4-amino-N-(1-((2-methoxy-5-(trifluoromethyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
15) 4-amino-N-(6-methyl-1-((4-(trifluoromethyl)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
16) 4-amino-N-(1-((4-methoxyphenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
17) 4-amino-N-(6-methyl-1-(p-tolylamino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
18) 4-amino-N-(1-((4-isopropylphenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
19) 4-amino-N-(1-((5-(t-butyl)isoxazol-3-yl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
20) 4-amino-N-(1-((4-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
21) 4-amino-N-(6-methyl-1-(thiazol-2-ylamino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
22) 4-amino-N-(1-((4-cyanophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
23) 4-amino-N-(6-methyl-1-(quinolin-5-ylamino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
24) 4-amino-N-(1-((4-ethoxyphenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
25) 4-amino-N-(6-methyl-1-((4-phenoxyphenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
26) 4-amino-N-(1-((4-hydroxyphenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
27) 4-amino-N-(1-((4-isopropoxyphenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
28) 4-amino-N-(1-((4-(dimethylamino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide 4-amino-N-(1-((4-dimethylaminophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
29) 4-amino-N-(1-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
30) 4-amino-N-(1-((3,4-dimethoxyphenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
31) 4-amino-N-(1-((3-fluoro-4-methoxyphenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
32) 4-amino-N-(6-methyl-1-((3,4,5-trimethoxyphenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
33) 4-amino-N-(6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
34) 4-amino-N-(1-(benzo[d][1,3]dioxol-5-ylamino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
35) 4-amino-N-(6-methyl-1-((5,6,7,8-tetrahydronaphthalen-2-yl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
36) 4-amino-N-(4-((4-chlorophenyl)amino)-7-methylquinazolin-8-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
37) 4-(cyclopropylamino)-N-(1-((4-methoxyphenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
38) 4-amino-N-(1-((3-chlorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
39) 4-amino-N-(1-((3-bromophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
40) 4-amino-N-(1-((2,4-dichlorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
41) 4-amino-N-(1-((3,4-dichlorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
42) 4-amino-N-(1-((3,5-dichlorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
43) 4-amino-N-(6-methyl-1-((3,4,5-trichlorophenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
44) 4-amino-N-(1-((4-chloro-3-methoxyphenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
45) 4-amino-N-(1-benzylamino-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
46) 4-amino-N-(6-methyl-1-phenoxyisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
47) 4-amino-N-(6-methyl-1-((4-morpholinophenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
48) N-(1-((4-(1H-pyrrol-1-yl)phenyl)amino)-6-methylisoquinolin-5-yl)-4-aminothieno[3,2-d]pyrimidine-7-carboxamide;
49) 4-amino-N-(6-methyl-1-(pyrimidin-4-ylamino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
50) 4-amino-N-(1-((4-(difluoromethoxy)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
51) 4-amino-N-(6-methyl-1-((4-(trifluoromethoxy)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
52) 4-amino-N-(1-((4-chlorophenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
53) 4-amino-N-(5-((4-chlorophenyl)amino)naphthalen-1-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
54) 4-amino-N-(1-((4-ethynylphenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
55) 4-amino-N-(1-(isopropylamino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
56) 4-amino-N-(1-(indolin-6-ylamino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
57) 4-amino-N-(1-((4-(fluoromethoxy)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
58) N-(1-(4-chlorophenylamino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
59) 4-amino-N-(1-((4-chloro-3-((dimethylamino)methyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
60) 4-amino-N-(1-((4-chloro-3-(pyrrolidin-1-ylmethyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
61) 4-amino-N-(1-((4-chloro-3-((diethylamino)methyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
62) 4-amino-N-(1-((1,4-diethyl-1,2,3,4-tetrahydroquinoxalin-6-yl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
63) 4-amino-N-(1-((4-chloro-3-(piperidin-1-ylmethyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
64) 4-amino-N-(1-((4-chloro-3-(morpholinomethyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
65) 4-amino-N-(1-((4-chloro-3-((4-methylpiperazin-1-yl)methyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
66) 4-amino-N-(1-((4-chloro-3-((diisopropylamino)methyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
67) 4-amino-N-(6-methyl-1-((3-(methylsulfonamido)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
68) tert-butyl 4-(5-((5-(4-aminothieno[3,2-d]pyrimidine-7-carboxamido)-6-methylisoquinolin-1-yl)amino)-2-chlorobenzyl)piperazine-1-carboxylate;
69) 4-amino-N-(1-((4-chloro-3-(piperazin-1-ylmethyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
70) 4-amino-N-(1-((3-chloro-4-methoxyphenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
71) 4-amino-N-(1-((3-(dimethylcarbamoyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
72) 4-amino-N-(6-methyl-1-((3-(methylcarbamoyl)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
73) 4-amino-N-(1-((4-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
74) 4-amino-N-(1-((4-bromo-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
75) 4-amino-N-(1-((4-methoxybenzyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
76) 4-amino-N-(1-((4-chlorobenzyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
77) 4-amino-N-(1-(2-(4-chlorophenyl)hydrazinyl)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
78) 4-amino-N-(1-((3-((dimethylamino)methyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
79) 4-amino-N-(6-methyl-1-((4-oxo-4H-chromen-6-yl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
80) N-(1-((3-acetylphenyl)amino)-6-methylisoquinolin-5-yl)-4-aminothieno[3,2-d]pyrimidine-7-carboxamide;
81) 4-amino-N-(1-((4-(2-methoxyethoxyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
82) 4-amino-N-(6-methyl-1-((3-(trifluoromethoxy)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
83) N-(1-((4-acetylphenyl)amino)-6-methylisoquinolin-5-yl)-4-aminothieno[3,2-d]pyrimidine-7-carboxamide;
84) 4-amino-N-(6-methyl-1-((4-(methylsulfonamido)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
85) 4-amino-N-(6-methyl-1-((3-(methylsulfonyl)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
86) 4-amino-N-(1-((4-chloro-3-(methoxymethyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
87) 4-amino-N-(1-((4-methoxy-3-(methylsulfonamido)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
88) 4-amino-N-(1-((4-chloro-3-(methylsulfonamido)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
89) 4-amino-N-(1-((6-chloropyridin-3-yl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
90) 4-amino-N-(1-((2-chloropyridin-4-yl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
91) 4-amino-N-(6-methyl(4-(methylsulfonamidomethyl)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
92) 4-amino-N-(6-methyl-1-((3-(methylsulfonamidomethyl)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
93) 4-amino-N-(1-((4-chloro-3-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
94) 4-amino-N-(1-((3-bromo-4-chlorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
95) 4-amino-N-(1-((4-(dimethylcarbamoyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
96) N-(1-((3-acetamidophenyl)amino)-6-methylisoquinolin-5-yl)-4-aminothieno[3,2-d]pyrimidine-7-carboxamide;
97) 4-amino-N-(6-methyl-1-((1-methyl-1H-indazol-6-yl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
98) 4-amino-N-(6-methyl-1-((4-(methylsulfinyl)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
99) 4-amino-N-(6-methyl-1-((2-methyl-1,3-dioxoisoindolin-5-yl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
100) 4-amino-N-(1-((6-methoxypyridin-3-yl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
101) 4-amino-N-(6-methyl-1-((3-(2,2,2-trifluoroacetyl)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
102) 4-amino-N-(6-methyl-1-((4-propionylphenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
103) 4-amino-N-(1-((4-hexanoylphenyl)amino)-6-methylisoquinolin-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
104) N-(1-((1-acetyl-1H-indazol-6-yl)amino)-6-methylisoquinolin-5-yl)-4-aminothieno[3,2-d]pyrimidine-7-carboxamide;
105) 4-amino-N-(1-((3-chloro-4-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
106) 4-amino-N-(6-methyl-1-((5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
107) 4-amino-N-(6-methyl-1-((2-methyl-2H-indazol-6-yl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
108) methyl 4-((5-(4-aminothieno[3,2-d]pyrimidine-7-carboxamido)-6-methylisoquinolin-1-yl)amino)benzoate;
109) 4-amino-N-(6-methyl-1-((1-methyl-1H-indazol-5-yl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
110) 4-amino-N-(6-methyl-1-((2-methyl-2H-indazol-5-yl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
111) 4-amino-N-(6-methyl-1-((6-methylpyridin-3-yl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
112) 4-amino-N-(6-methyl-1-((1-methyl-1H-indol-6-yl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
113) tert-butyl 6-((5-(4-aminothieno[3,2-d]pyrimidine-7-carboxamido)-6-methylisoquinolin-1-yl)amino)-1H-indazol-1-carboxylate;
114) N-(1-((1H-indazol-6-yl)amino)-6-methylisoquinolin-5-yl)-4-aminothieno[3,2-d]pyrimidine-7-carboxamide hydrochloride;
115) 4-amino-N-(1-((5-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
116) 4-amino-N-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
117) 4-amino-N-(1-((3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
118) 4-amino-N-(1-((3-chloro-1-methyl-1H-indazol-6-yl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
119) 4-amino-N-(6-methyl-1-((4-(prop-2-yn-1-yloxy)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
120) 4-amino-N-(1-((2-methoxy-4-morpholinophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
121) 4-amino-N-(1-(benzo[d]thiazol-6-ylamino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
122) N-(1-((1H-indazol-5-yl)amino)-6-methylisoquinolin-5-yl)-4-aminothieno[3,2-d]pyrimidine-7-carboxamide; and
123) 4-amino-N-(1-((3-chloro-2,4-difluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide;
124) 4-amino-N-(1-((3-(dimethylamino)propyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide; and
125) 4-amino-N-(6-methyl-1-(piperidin-1-yl)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide,
or its a pharmaceutically acceptable salt thereof.
7. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, as an active ingredient.
8. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition further comprises a drug selected from the group consisting of cell signal transduction inhibitors, mitosis inhibitors, alkylating agents, antimetabolites, antibiotics, growth factor inhibitors, cell cycle inhibitors, topoisomerase inhibitors, biological reaction modifiers, antihormonal agents, antiandrogen, cell differentiation/proliferation/survival inhibitors, apoptosis inhibitors, inflammation inhibitors and P-glycoprotein inhibitors.
9. A pharmaceutical formulation comprising the pharmaceutical composition of claim 7 .
10. The pharmaceutical formulation of claim 9 , wherein said formulation is an oral formulation.
11. The pharmaceutical formulation of claim 9 , wherein said formulation is in the form of a tablet, a pill, powder, a capsule, syrup, an emulsion or a microemulsion.
12. A method for manufacturing a medicament containing the compound of claim 1 , or a pharmaceutically acceptable salt thereof, as an active ingredient, said method comprising formulating the compound of claim 1 , or a pharmaceutically acceptable salt thereof, into the medicament together with a pharmaceutically acceptable carrier.
13. A method for treating a cancer, which method comprises administering the compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a mammal in need thereof, wherein the cancer is liver cancer or melanoma.
14. The method of claim 13 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered in combination with a drug selected from the group consisting of cell signal transduction inhibitors, mitosis inhibitors, alkylating agents, antimetabolites, antibiotics, growth factor inhibitors, cell cycle inhibitors, topoisomerase inhibitors, biological reaction modifiers, antihormonal agents, antiandrogen, cell differentiation/proliferation/survival inhibitors, apoptosis inhibitors, inflammation inhibitors, and P-glycoprotein inhibitors.
15. A thieno[3,2-d]pyrimidine compound selected from the group consisting of:
71) 4-amino-N-(1-((3-(dimethylcarbamoyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide; 72) 4-amino-N-(6-methyl-1-((3-(methylcarbamoyl)phenyl)amino)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide; 81) 4-amino-N-(1-((4-(2-methoxyethoxy)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide; 95) 4-amino-N-(1-((4-(dimethylcarbamoyl)phenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide; 124) 4-amino-N-(1-((3-(dimethylamino)propyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide; and 125) 4-amino-N-(6-methyl-1-(piperidin-1-yl)isoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide; or a pharmaceutically acceptable salt thereof.
16. A pharmaceutical composition comprising a compound of claim 15, or a pharmaceutically acceptable salt thereof, as an active ingredient.
17. The pharmaceutical composition of claim 16, wherein the pharmaceutical composition further comprises a drug selected from the group consisting of cell signal transduction inhibitors, mitosis inhibitors, alkylating agents, antimetabolites, antibiotics, growth factor inhibitors, cell cycle inhibitors, topoisomerase inhibitors, biological reaction modifiers, antihormonal agents, antiandrogen, cell differentiation/proliferation/survival inhibitors, apoptosis inhibitors, inflammation inhibitors and P-glycoprotein inhibitors.
18. A pharmaceutical formulation comprising the pharmaceutical composition of claim 16.
19. The pharmaceutical formulation of claim 18, wherein said formulation is an oral formulation.
20. The pharmaceutical formulation of claim 18, wherein said formulation is in the form of a tablet, a pill, powder, a capsule, syrup, an emulsion or a microemulsion.
21. A method for treating cancer, which method comprises administering the pharmaceutical composition of claim 16 to a mammal in need thereof, wherein the cancer is liver cancer or melanoma.
22. The method of claim 21, wherein the pharmaceutical composition is administered in combination with a drug selected from the group consisting of cell signal transduction inhibitors, mitosis inhibitors, alkylating agents, antimetabolites, antibiotics, growth factor inhibitors, cell cycle inhibitors, topoisomerase inhibitors, biological reaction modifiers, antihormonal agents, antiandrogen, cell differentiation/proliferation/survival inhibitors, apoptosis inhibitors, inflammation inhibitors and P-glycoprotein inhibitors.
23. A thieno[3,2-d]pyrimidine compound having the following structure:
or a pharmaceutically acceptable salt thereof.
24. A pharmaceutical composition comprising the thieno[3,2-d]pyrimidine compound of claim 23, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
25. A method of treating a cancer, the method comprising administering the pharmaceutical composition of claim 24 to a mammal in need thereof, wherein the cancer is liver cancer or melanoma.
26. The method of claim 25 wherein the pharmaceutical composition is administered in combination with a cell signal transduction inhibitor drug.
27. A thieno[3,2-d]pyrimidine compound having the following structure:
or a pharmaceutically acceptable salt thereof.
28. A pharmaceutical composition comprising the thieno[3,2-d]pyrimidine compound of claim 27, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
29. A method of treating a cancer, the method comprising administering the pharmaceutical composition of claim 28 to a mammal in need thereof, wherein the cancer is liver cancer or melanoma.
30. The method of claim 31 wherein the pharmaceutical composition is administered in combination with a cell signal transduction inhibitor drug.
31. A thieno[3,2-d]pyrimidine compound having the following structure:
or a pharmaceutically acceptable salt thereof.
32. A pharmaceutical composition comprising the thieno[3,2-d]pyrimidine compound of claim 31, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
33. A method of treating a cancer, the method comprising administering the pharmaceutical composition of claim 32 to a mammal in need thereof, wherein the cancer is liver cancer or melanoma.
34. The method of claim 33 wherein the pharmaceutical composition is administered in combination with a cell signal transduction inhibitor drug.
35. A thieno[3,2-d]pyrimidine compound having the following structure:
or a pharmaceutically acceptable salt thereof.
36. A pharmaceutical composition comprising the thieno[3,2-d]pyrimidine compound of claim 35, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
37. A method of treating a cancer, the method comprising administering the pharmaceutical composition of claim 36 to a mammal in need thereof, wherein the cancer is liver cancer or melanoma.
38. The method of claim 37 wherein the pharmaceutical composition is administered in combination with a cell signal transduction inhibitor drug.
39. A thieno[3,2-d]pyrimidine compound having the following structure:
or a pharmaceutically acceptable salt thereof.
40. A pharmaceutical composition comprising the thieno[3,2-d]pyrimidine compound of claim 39, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
41. A method of treating a cancer, the method comprising administering the pharmaceutical composition of claim 40 to a mammal in need thereof, wherein the cancer is liver cancer or melanoma.
42. The method of claim 41 wherein the pharmaceutical composition is administered in combination with a cell signal transduction inhibitor drug.
43. A thieno[3,2-d]pyrimidine compound having the following structure:
or a pharmaceutically acceptable salt thereof.
44. A pharmaceutical composition comprising the thieno[3,2-d]pyrimidine compound of claim 43, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
45. A method of treating a cancer, the method comprising administering the pharmaceutical composition of claim 44 to a mammal in need thereof, wherein the cancer is liver cancer or melanoma.
46. The method of claim 45 wherein the pharmaceutical composition is administered in combination with a cell signal transduction inhibitor drug.
47. A thieno[3,2-d]pyrimidine compound having the following structure:
or a pharmaceutically acceptable salt thereof.
48. A pharmaceutical composition comprising the thieno[3,2-d]pyrimidine compound of claim 47, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
49. A method of treating a cancer, the method comprising administering the pharmaceutical composition of claim 48 to a mammal in need thereof, wherein the cancer is liver cancer or melanoma.
50. The method of claim 49 wherein the pharmaceutical composition is administered in combination with a cell signal transduction inhibitor drug.
51. A thieno[3,2-d]pyrimidine compound having the following structure:
or a pharmaceutically acceptable salt thereof.
52. A pharmaceutical composition comprising the thieno[3,2-d]pyrimidine compound of claim 51, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
53. A method of treating a cancer, the method comprising administering the pharmaceutical composition of claim 52 to a mammal in need thereof, wherein the cancer is liver cancer or melanoma.
54. The method of claims 53 wherein the pharmaceutical composition is administered in combination with a cell signal transduction inhibitor drug.
55. A method of preparing a thieno[3,2-d]pyrimidine compound, or a pharmaceutically acceptable salt thereof, according to reaction steps 1 to 3:
wherein:
A is C 6-10 aryl or 5- to 10-membered heteroaryl;
Z is hydrogen, C 1-3 alkyl or NR 3 R 4 , wherein said R 3 and R 4 are each independently hydrogen, C 1-6 alkyl or —(CH 2 ) q -B—, B representing NR 5 R 6 , C 1-6 alkoxy, C 3-6 cycloalkyl or 3- to 6-membered heterocycloalkyl;
R 1 is hydrogen, halogen, C 1-3 alkyl or C 1-3 alkoxy, wherein said alkyl or alkoxy is unsubstituted or substituted with one or more halogen atoms;
R 2 is hydrogen, halogen, —CF 3 , —NO 2 , —OH, —CN, C 1-6 alkoxy, C 1-6 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, —NR 7 R 8 , —NHSO 2 R 9 , —SO 2 R 10 , —C(O)R 11 , —NHC(O)R 12 , —NHC(O)OR 13 , —S(O)R 14 , C 3-6 cycloalkyl, 3- to 6-membered heterocycloalkyl, C 6-10 aryl, C 6-10 aryloxy, 5- to 10-membered heteroaryl or 5- to 10-membered heteroaryloxy, wherein said R 2 is connected to A by —(CH 2 ) p - or substituted with C 1-4 alkyl, C 2-4 alkynyl, C 1-4 alkylcarbonyl or one or more halogen atoms;
R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 are each independently hydrogen, —NH 2 , C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl or 3-to 6-membered heterocycloalkyl, said alkyl, alkoxy, cycloalkyl or heterocycloalkyl being unsubstituted or substituted with one or more halogen atoms;
m is an integer ranging from 0 to 3;
q is 0;
p is an integer ranging from 0 to 1; and
n is 0 or 1.
56. The method of claim 55 wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof.
57. The method of claim 55 wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof.
58. The method of claim 55 wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof.
59. The method of claim 55 wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof.
60. The method of claim 55 wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof.
61. The method of claim 55 wherein the compound is:
or a pharmaceutically acceptable salt thereof.
62. The method of claim 55 wherein the compound is:
or a pharmaceutically acceptable salt thereof.
63. The method of claim 55 wherein the compound is:
or a pharmaceutically acceptable salt thereof.Cited by (0)
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