IP Library › Granted Patent US 7,405,299
Granted Patent B2
US 7,405,299 · App. 10/535,381 · Granted Jul 29, 2008

Compounds as pharmaceutical agents

Assignee: Eli Lilly and Company
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Quick Facts
Patent No.
US 7,405,299
App. No.
10/535,381
Granted
Jul 29, 2008
Kind
B2
Abstract

The current invention relates to compounds of the formula: (Ia) and the pharmaceutically acceptable salts thereof and their use as TGF-beta signal transduction inhibitors for treating cancer and other diseases in a patient in need thereof by administration of said compounds.

Claims (97)

1. A compound selected from the group of:

a) 2-(Pyridin-2-yl)-3-(thiophen-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

b) 5-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-indole;

c) 3-(2-Phenyl-oxazol-5-yl)-2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

d) 4-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo [1,2-b]pyrazol-3-yl]-benzo[2,1,3]thiadiazole;

e) 5-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]benzo[2,1,3]thiadiazole;

f) 6-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoxaline;

g) 5-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoxaline;

h) 2-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo [1,2-b]pyrazol-3-yl]-1H-imidazo[4,5-b]pyridine;

i) 2-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-imidazo[4,5-c]pyridine;

j) 2-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-benzoimidazole;

k) 2-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-oxazolo[4,5-b]pyridine;

l) 2-Dimethylamino-N-[6-[2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-[1,8]naphthyridin-2-yl]-acetamide;

m) 4-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-[1,8]naphthyridine;

n) 2-(Pyridin-2-yl)-3-(imidazo[1,2-a]pyridin-6-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

o) 7-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-isoquinoline;

p) 4-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-isoquinoline;

q) 3-(4-Fluoro-benzofuran-7-yl)-2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

r) 2-Methyl-5-[2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-benzothiazole;

s) 2-Methyl-5-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-benzothiazole;

t) 3-(4-Fluoro-benzofuran-7-yl)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

u) 7-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-isoquinoline;

v) 1-Methyl-5-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-indole;

w) 1-Methyl-5-[2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H indole;

x) 3-(Pyrazin-2-yl)-2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

y) 2-(6-Methyl-pyridin-2-yl)-3-(pyrazin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

z) 3-(2,3-Dihydro-benzofuran-5-yl)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

aa) 3-(Furan-3-yl-2)-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

bb) 3-(Furan-3-yl)-2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

cc) 2-(6-Methyl-pyridin-2-yl)-3-(thiophen-3-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

dd) 3-(Benzofuran-5-yl)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

ee) 6-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-pyrazolo[1,5-a]pyrimidine;

ff) 3-(3,4-Dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

gg) 3-Morpholin-4-ylmethyl-6-[2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridine;

hh) 1-Morpholin-4-yl-2-[6-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-imidazo[1,2-a]pyridin-3-yl]-ethanone;

ii) 6-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridine-3-carboxylic acid;

jj) 6-[2-(Pyridin-2-yl)-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyridin-3-yl]-imidazo[1,2-a]pyridine;

kk) 1-Morpholin-4-yl-2-[6-(2-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-imidazo[1,2-a]pyridin-2-yl]-ethanone;

ll) 6-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridine-3-carboxylic acid (2-dimethylamino-ethyl)-amide;

mm) 6-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester;

nn) 6-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridine-2-carboxylic acid amide;

oo) 8-Fluoro-6-[2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridine;

pp) [6-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridin-3-yl]-(1,1,3,3-tetramethyl-butyl)-amine;

qq) N-[6-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridin-3-yl]-acetamide;

rr) 6-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridine-3-carboxylic Acid Amide;

ss) 6-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridine-2-carboxylic Acid (2-Dimethylamino-ethyl)-amide;

tt) 6-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridine-3-carboxylic Acid Amide;

uu) 7-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-imidazo[1,2-a]pyridine;

vv) 3-(4-Chloro-phenyl)-6-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b)pyrazol-3-yl]-imidazo[1,2-a]pyridine;

ww) 5-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-benzoimidazole;

xx) 1-Methyl-6-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-benzoimidazole;

yy) 1-Methyl-6-[2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-benzoimidazole;

zz) 1-Methyl-5-[2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-benzoimidazole;

aaa) 1-Methyl-5-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-benzoimidazole;

bbb) 5-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1-[3-(tetrahydro-pyran-2-yloxy)-propyl]-1H-benzoimidazole;

ccc) 6-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1-[3-(tetrahydro-pyran-2-yloxy)-propyl]-1H-benzoimidazole;

ddd) 5-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1-[3-(tetrahydro-pyran-2-yloxy)-propyl]-1H-benzoimidazole;

eee) 6-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1-[3-(tetrahydro-pyran-2-yloxy)-propyl]-1H-benzoimidazole;

fff) 2-{7-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-pyrido[2,3-b]pyrazin-2-yloxy}-ethanol (Ex. 55a)

ggg) 7-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-quinoxalin-2-one;

hhh) 3-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl][1,5]naphthyridine (Ex. 55c)

iii) 3-[6-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo [1,2-b]pyrazol-3-yl]-benzoimidazol-1-yl]-propan-1-ol;

jjj) 3-[6-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-benzoimidazol-1-yl]-propan-1-ol;

kkk) Methanesulfonic Acid 3-[6-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-benzoimidazol-1-yl]-propyl Ester;

lll) Methanesulfonic acid 3-[6-[2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-benzoimidazol-1-yl]-propyl ester (Ex. 57b)

mmm) Dimethyl-[3-[6-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-benzoimidazol-1-yl]propyl]amine;

nnn) Diethyl-[3-[6-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-benzoimidazol-1-yl]propyl]amine;

ooo) 6-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1-(3-morpholin-4-yl-propyl)-1H-benzoimidazole;

ppp) 6-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1-(3-pyrrolidin-1-yl-propyl)-1H-benzoimidazole;

qqq) 6-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1-(3-piperidin-1-yl-propyl)-1H-benzoimidazole;

rrr) 5-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-benzoimidazole;

sss) 6-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoxaline;

ttt) 2-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoxaline;

uuu) 2-[7-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoxalin-2-yloxy]-ethanol;

vvv) 4-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-[1,6]naphthyridine;

www) 6-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-isoquinoline;

xxx) 6-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-benzothiazole;

yyy) 2-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-benzothiazole;

zzz) 5-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-benzothiazol-2-ylamine;

aaaa) 4-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-indole;

bbbb) 3-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-indole;

cccc) 3-(2,3-Dihydro-benzofuran-5-yl)-2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

dddd) Acetic acid 5-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-benzofuran-3-yl ester;

eeee) 3-(5-Methoxy-benzofuran-3-yl)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

ffff) 5-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-benzofuran-2-carboxylic acid;

gggg) 3-(Benzofuran-2-yl)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole;

hhhh) 5-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-pyrazolo[1,5-a]pyrimidine;

iiii) 5-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-pyrazolo[1,5-a]pyrimidine;

jjjj) 5-[2-(Pyridin-2-yl)-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyridin-3-yl]-pyrazolo[1,5-a]pyrimidine;

kkkk) 8-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-[1,6]naphthyridine;

llll) 3-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-pyrazolo[1,5-a]pyrimidine;

mmmm) 2-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-[1,5]naphthyridine;

nnnn) 2-Chloro-7-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoxaline;

oooo) Dimethyl-(2-{7-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoxalin-2-yloxy}-ethyl)-amine;

pppp) Dimethyl-(2-{7-[2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoxalin-2-yloxy}-propyl)-amine;

qqqq) 7-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoxaline-2-carboxylic acid amide;

or a pharmaceutically acceptable salt thereof.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 22, 2006
From: BEIGHT, DOUGLAS WADE; BURKHOLDER, TIMOTHY PAUL; DECOLLO, TODD VINCENT; GODFREY, ALEXANDER GLENN; HEAP, CHARLES RAYMOND; KING, CHI-HSIN RICHARD; LI, HONG-YN; MCMILLEN, WILLIAM THOMAS; WANG, YAN; DIEFENBACHER, CLIVE GIDEON; ENGLER, THOMAS ALBERT; MALHOTRA, SUSHANT; MURULLA, SREENIVASA REDDY; SAWYER, JASON SCOTT
To: ELI LILLY AND COMPANY
Reel/Frame 017364/0829 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 16, 2005
From: BEIGHT, DOUGLAS WADE; BURKHOLDER, TIMOTHY PAUL; DECOLLO, TODD VINCENT; GODFREY, ALEXANDER GLENN; HEAP, CHARLES RAYMOND; KING, CHI-HSIN RICHARD; LI, HONG-YU; MCMILLEN, WILLIAM THOMAS; WANG, YAN; DIEFENBACHER, CLIVE GIDEON; ENGLER, THOMAS ALBERT; MAHOTRA, SUSHANT; MUNDLA, SCREENIVASA READY; SAWYER, JASON SCOTT
To: ELI LILLY AND COMPANY
Reel/Frame 017298/0005 →
Continuity (1)
Related Publication 20060058295A1 · Mar 16, 2006