US 7,517,995 B2
Thiazolyl-dihydro-cyclopentapyrazole
Steffen Breitfelder, Assmannshardt (Germany); Udo Maier, Senden (Germany); Christoph Hoenke, Ingelheim (Germany); Anne T. Joergensen, Biberach (Germany); Alexander Pautsch, Ulm (Germany); Trixi Brandl, Basel (Switzerland); Matthias Grauert, Biberach (Germany); Matthias Hoffmann, Mittelbiberach (Germany); Stefan Scheuerer, Warthausen (Germany); Klaus Erb, Mittelbiberach (Germany); Michael Pieper, Biberach (Germany); and Ingo Pragst, Munich (Germany)
Assigned to Boehringer Ingelheim International GmbH, Ingelheim (Germany)
Filed on Mar. 23, 2007, as Appl. No. 11/690,356.
Claims priority of application No. 06112298 (EP), filed on Apr. 06, 2006.
Prior Publication US 2007/0238730 A1, Oct. 11, 2007
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/429 (2006.01); C07D 513/04 (2006.01)
U.S. Cl. 548—151  [514/366] 11 Claims
 
1. A compound of the formula (I),

OG Complex Work Unit Drawing
wherein
Ra denotes hydrogen or an optionally substituted group selected from among C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl, C3-C8-cycloalkyl, C3-C8-cycloalkenyl, C1-C6-haloalkyl, C6-C14-aryl, C6-C14-aryl-C1-C5-alkyl, C5-C10-heteroaryl, C3-C8-cycloalkyl-C1-C4-alkyl, C3-C8-cycloalkenyl-C1-C4-alkyl, C5-C10-heteroaryl-C1-C4-alkyl, C9-C13-spiro, C3-C8-heterocycloalkyl and C3-C8-heterocycloalkyl-C1-C4-alkyl ;
Rb denotes NH2 OH,
or
an optionally substituted group selected from among C1-C8-alkyl, C3-C8-cycloalkyl, C2-C8-alkenyl, C2-C8-alkynyl, C3-C8-cycloalkenyl, C1-C6-haloalkyl, C6-C14-aryl, C6-C14-aryl-C1-C5-alkyl, C5-C10-heteroaryl, C3-C8-cycloalkyl-C1-C4-alkyl, C3-C8-cycloalkenyl-C1-C4-alkyl, C5-C10-heteroaryl-C1-C4-alkyl, C9-C13-spiro, C3-C8-heterocycloalkyl, CONH2, C6-C14-aryl-NH, C3-C8-heterocycloalkyl-NH- and OMe;
R1 denotes hydrogen or an optionally substituted group selected from among C1-C8-alkyl, C3-C8-cycloalkyl, C2-C8-alkenyl, C2-C8-alkynyl and C6-C14-aryl-C1-C5-alkyl-;
or
R2 denotes hydrogen or an optionally substituted group selected from among C1-C8-alkyl, C3-C8-cycloalkyl, C2-C8-alkenyl, C3-C8-cycloalkenyl, C1-C6-haloalkyl, C6-C14-aryl, C6-C14-aryl-C1-C5-alkyl, C5-C10-heteroaryl, C3-C8-cycloalkyl-C1-C4-alkyl, C3-C8-cycloalkenyl -C1-C4-alkyl, C5-C10-heteroaryl-C1-C6-alkyl, C9-C13-spiro, C3-C8-heterocycloalkyl, C3-C8- heterocycloalkyl-C1-C6-alkyl- and C6-C14-aryl-C1-C6-alkyl-;
or
R1 and R2 together form an optionally substituted five-, six- or seven-membered ring consisting of carbon atoms and optionally 1 to 2 heteroatoms, selected from among oxygen, sulphur and nitrogen,
or
R1 and R2 together form an optionally substituted nine- to thirteen-membered spirocyclic ring,
or
R2 denotes a group selected from among general formulae (A1) to (A18)

OG Complex Work Unit Drawing

OG Complex Work Unit Drawing
wherein
X and Y may be linked to the same or different atoms of G, and
X denotes a bond or an optionally substituted group selected from among C1-C7-alkylene, C3-C7-alkenylene and C3-C7-alkynylene,
or
X together with R1, R3 or R4 may form a C1-C7-alkylene bridge;
Y denotes a bond or optionally substituted C1-C4-alkylene;
Q denotes an optionally substituted group selected from among C1-C7-alkylene, C3-C7-alkenylene and C3-C7-alkynylene; or
Q together with R1, R3 or R4 may form a C1-C7-alkylene bridge;
R3, R4 and R5 which may be identical or different, denote hydrogen or an optionally substituted group selected from among C1-C8-alkyl, C3-C8-cycloalkyl, C2-C6-haloalkyl, C1-C4-alkyl-C3-C8-cycloalkyl, C3-C8-cycloalkyl-C1-C4-alkyl, NR7R8, NR7R8-C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkoxy-C1-C4-alkyl, C6-C14-aryl and C5-C10-heteroaryl;
or in each case two of the substituents
R3, R4 and R5 together form an optionally substituted five-, six- or seven -membered ring, consisting of carbon atoms and optionally 1-2 heteroatoms, selected from among oxygen, sulphur and nitrogen;
G denotes a saturated, partially saturated or unsaturated ring system consisting of 3-10 C atoms, wherein optionally up to 6 C atoms are replaced by heteroatoms selected from among nitrogen, oxygen and sulphur;
R6 which may be identical or different, denote hydrogen or an optionally substituted group selected from among C1-C8-alkyl, C2-C6-alkenyl C3-C8-cycloalkyl, C2-C6- haloalkyl, C6-C14-aryl, C5-C10-heteroaryl and and C3-C8-heterocycloalkyl,
or
a group selected from among ═O, NR7R8OR , —CO—C1-C3-alkyl -NR7R8, —O—C1-C3-alkyl-NR7R8, CONR7R8, NR7COR8, —CO—C1-C3-alkyl-NR7(CO)OR8, —O(CO)NR7R8, NR7(CO)NR8R9, NR7(CO)OR8, (CO)OR7, —O(CO)R7, COR7, (SO)R7, (SO2)R7, (SO2)NR7R8, NR7(SO2)R8, NR7(SO2)NR8R9, CN, —C1-C3-alkyl-C6-C14-aryl , —NH-CO—NH—C1-C3-alkyl and halogen;
n denotes 1, 2 or 3;
R7, R8 and R9 which may be identical or different, denote hydrogen or an optionally substituted group selected from among C1-C8-alkyl, C3-C8-cycloalkyl, C1-C6-haloalkyl, C1- C4-alkyl-C3-C8-cycloalkyl, C3-C8-cycloalkyl-C1-C3-alkyl, C6-C14-aryl, C1-C4-alkyl-C6-C14-aryl, C6-C14-aryl-C1-C4-alkyl, C3-C8-heterocycloalkyl, C1-C5-alkyl-C3-C8-heterocycloalkyl, C3-C8-heterocycloalkyl-C1-C4-alkyl, C1-C4-alkyl(CO) and C1-C4-alkyl—O(CO)—;
or in each case two of the substituents
R7, R8 and R9 together optionally substituted five-, six- seven-membered ring, consisting of carbon atoms and optionally 1-2 heteroatoms, selected from among oxygen, sulphur and nitrogen; optionally in the form of the tautomers, the racemates, the enantiomers, the diastereomers and the mixtures thereof, as well as optionally the pharmacologically acceptable acid addition salts thereof;
with the proviso that the following compounds are excluded:
a) 1,1-dimethyl-3-(4-phenyl-4,7-dihydro-3-thia-1,4,5-triaza-cyclopenta[a]pentalen-2-yl) -urea
b) (4-phenyl-4,7-dihydro-3 -thia- 1 ,4,5-triaza-cyclopenta[a]pentalen-2-yl)-urea
c) 1-(2-dimethylamino-ethyl)-3-(4-phenyl-4,7-dihydro-3-thia-1,4,5-triaza -cyclopenta[a]pentalen-2-yl)-urea
d) 1-(2-dimethylamino-ethyl)-1-methyl-3-(4-phenyl-4,7-dihydro-3-thia-1,4,5-triaza -cyclopenta[a]pentalen-2-yl)-urea
e) 4-methyl-piperazine-1-carboxylic acid (4-phenyl-4,7-dihydro-3-thia-1,4,5-triaza -cyclopenta[a]pentalen-2-yl)-amide
f) 1-[4-(2-chloro-phenyl)-4,7-dihydro-3-thia-1,4,5-triaza-cyclopenta[a]pentalen-2-yl]-3-(2-dimethylamino-ethyl)-urea
g) 3-[4-(2-chloro-phenyl)-4,7-dihydro-3-thia-1,4,5 -triaza-cyclopenta[a]pentalen-2-yl]-1-(2-dimethylamino-ethyl)- 1-methyl-urea
h) 1-[4-(2-chloro-phenyl)-4,7-dihydro-3-thia-1,4,5-triaza-cyclopenta[a]pentalen-2-yl]-3-methyl-urea
i) 1-[4-(2-chloro-phenyl)-4,7-dihydro-3-thia-1,4,5-triaza-cyclopenta[a]pentalen-2-yl]-3-(2-imidazol-1-yl-ethyl)-urea
j) 3-4-(2-chloro-phenyl)-4,7-dihydro-3-thia-1,4,5-triaza-cyclopenta[a]pentalen-2-yl]-1,1-dimethyl-urea, and
k) piperidine-1-carboxylic acid (4-phenyl-4,7-dihydro-3-thia-1,4,5-triaza -cyclopenta[a]pentalen-2-yl)-amide.