Claims for Patent: 7,803,810

Summary for Patent: 7,803,810

Title:	Inhibitors
Abstract:	Compounds of formula (I), combinations and uses thereof for disease therapy, ##STR00001## or a pharmaceutically acceptable salt or solvate thereof, including all tautomers, stereoisomers and polymorphs thereof wherein: R.sup.1 represents C.sub.2-8alkyl; C.sub.2-8alkenyl; --(C.sub.1-6alkyl)-aryl; --(C.sub.1-6alkyl)-heteroaryl; --(C.sub.1-6alkyl)-carbocyclyl; --(C.sub.1-6alkyl)-heterocyclyl; -aryl; -heteroaryl; -carbocyclyl or -heterocyclyl; wherein said aryl or heteroaryl groups may be optionally substituted by one or more substituents selected from, C.sub.1-4alkyl, C.sub.1-4-fluoroalkyl, C.sub.1-4alkoxy, C.sub.1-4-fluoroalkoxy, hydroxy, --SO.sub.2(C.sub.1-4alkyl), --SO.sub.2N(C.sub.1-4alkyl)(C.sub.1-4alkyl), --SOC.sub.1-4alkyl, --SOC.sub.3-6cycloalkyl --C(O)O(C.sub.1-4alkyl), benzyloxy and phenyl; and wherein said carbocyclyl and heterocyclyl groups may be optionally substituted by one or more substituents selected from --C.sub.1-4 alkyl, --C.sub.1-4 alkoxy, hydroxyl, halogen and oxo; R.sup.2 represents H; C.sub.1-4alkyl or halogen; R.sup.3 represents H; C.sub.1-4alkyl or halogen; and R.sup.4 represents H; C.sub.1-4alkyl or halogen.
Inventor(s):	Ramsbeck; Daniel (Halle/Saale, DE), Heiser; Ulrich (Halle/Saale, DE), Buchholz; Mirko (Halle/Saale, DE), Niestroj; Andre J. (Sennewitz, DE)
Assignee:	Probiodrug AG (Halle/Saale, DE)
Application Number:	12/045,163
Patent Claims:	1. A compound of formula (I), ##STR00045## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 represents C.sub.2-8alkyl; C.sub.2-8alkenyl; --(C.sub.1-6alkyl)-aryl; --(C.sub.1-6alkyl)-heteroaryl; --(C.sub.1-6alkyl) -carbocyclyl; --(C.sub.1-6alkyl)-heterocyclyl; -aryl; -heteroaryl; -carbocyclyl or -heterocyclyl; wherein said aryl or heteroaryl groups may be optionally substituted by one or more substituents selected from, C.sub.1-4alkyl, C.sub.1-4fluoroalkyl, C.sub.1-4alkoxy, C.sub.1-4fluoroalkoxy, hydroxy, --SO.sub.2(C.sub.1-4alkyl), --SO.sub.2N(C.sub.1-4alkyl)(C.sub.1-4alkyl), SOC.sub.1-4alkyl, --SOC.sub.3-6cycloalkyl, --C(O)O(C.sub.1-4alkyl), benzyloxy and phenyl; and wherein said carbocyclyl and heterocyclyl groups may be optionally substituted by one or more substituents selected from --C.sub.1-4 alkyl, --C.sub.1-4 alkoxy, hydroxyl, halogen and oxo; R.sup.2 represents H; C.sub.1-4alkyl or halogen; R.sup.3 represents H; C.sub.1-4alkyl or halogen; and R.sup.4 represents H; C.sub.1-4alkyl or halogen. 2. A compound according to claim 1 wherein R.sup.1 represents C.sub.2-8alkyl; C.sub.2-8alkenyl; --(C.sub.1-6alkyl)-aryl; --(C.sub.1-6alkyl)-heteroaryl; --(C.sub.1-6alkyl)-carbocyclyl; --(C.sub.1-6alkyl)-heterocyclyl; -aryl; -heteroaryl; -carbocyclyl or -heterocyclyl; wherein said aryl or heteroaryl groups may be optionally substituted by one or more substituents selected from, C.sub.1-4alkyl, C.sub.1-4fluoroalkyl, C.sub.1-4alkoxy, C.sub.1-4fluoroalkoxy, hydroxy, --SO.sub.2(C.sub.1-4alkyl), --SO.sub.2N(C.sub.1-4alkyl)(C.sub.1-4alkyl), --C(O)O(C.sub.1-4alkyl), benzyloxy and phenyl; and wherein said carbocyclyl and heterocyclyl groups may be optionally substituted by one or more substituents selected from --C.sub.1-4 alkyl, --C.sub.1-4 alkoxy, hydroxyl and halogen. 3. A compound according to claim 1 wherein R.sup.1 represents C.sub.2-8alkyl, --(C.sub.1-6alkyl)-aryl, heteroaryl or -aryl. 4. A compound according to claim 1 wherein R.sup.1 represents -alkyl-aryl in which aryl may optionally be substituted. 5. A compound according to claim 1 wherein R.sup.1 represents aryl in which aryl may optionally be substituted. 6. A compound according to claim 5 wherein R.sup.1 represents optionally substituted phenyl. 7. A compound according to claim 1 wherein R.sup.2 represents H. 8. A compound according to claim 1 wherein R.sup.3 represents H. 9. A compound according to claim 1 wherein R.sup.4 represents H. 10. A compound selected from the group consisting of: 8-butylH-imidazo[1,5-a]pyridine; 8-benzylH-imidazo[1,5-a]pyridine; 8-isobutylH-imidazo[1,5-a]pyridine; 8-phenylH-imidazo[1,5-a]pyridine; 8-(2-fluorophenyl)H-imidazo[1,5-a]pyridine; 8-(3-fluorophenyl)H-imidazo[1,5-a]pyridine; 8-(3-fluorophenyl)H-imidazo[1,5-a]pyridine; 8-(2-chlorophenyl)H-imidazo[1,5-a]pyridine; 8-(3-chlorophenyl)H-imidazo[1,5-a]pyridine; 8-(4-chlorophenyl)H-imidazo[1,5-a]pyridine; 8-(2-(trifluoromethyl)phenyl)H-imidazo[1,5-a]pyridine; 8-(2-methoxyphenyl)H-imidazo[1,5-a]pyridine; 8-(3-methoxyphenyl)H-imidazo[1,5-a]pyridine; 8-(4-methoxyphenyl)H-imidazo[1,5-a]pyridine; 8-(2-(benzyloxy)phenyl)H-imidazo[1,5-a]pyridine; 8-(3-(benzyloxy)phenyl)H-imidazo[1,5-a]pyridine; 8-(4-(benzyloxy)phenyl)H-imidazo[1,5-a]pyridine; 8-(biphen-2-yl)H-imidazo[1,5-a]pyridine; 8-(biphen-3-yl)H-imidazo[1,5-a]pyridine; 8-(biphen-4-yl)H-imidazo[1,5-a]pyridine; 8-(2-(trifluoromethoxy)phenyl)H-imidazo[1,5-a]pyridine; 8-(4-ethoxyphenyl)H-imidazo[1,5-a]pyridine; 8-(benzo[d][1,3]dioxol -6-yl)H-imidazo[1,5-a]pyridine; 8-(4-methoxy-3-methylphenyl)H-imidazo[1,5-a]pyridine; 8-(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)H-imidazo[1,5-a]pyridine; 8-(3,4-dimethoxyphenyl)H-imidazo[1,5-a]pyridine; and 8-(4-methoxy-3,5-dimethylphenyl)H-imidazo[1,5-a]pyridine; or a pharmaceutically acceptable salt of any one thereof. 11. A compound according to claim 1, wherein the compound is selected from the group consisting of: 8-butylH-imidazo[1,5-a]pyridine; 8-benzylH-imidazo[1,5-a]pyridine; 8-isobutylH-imidazo[1,5-a]pyridine; 8-phenylH-imidazo[1,5-a]pyridine; 8-(3-fluorophenyl)H-imidazo[1,5-a]pyridine; 8-(3-fluorophenyl)H-imidazo[1,5-a]pyridine; 8-(3-chlorophenyl)H-imidazo[1,5-a]pyridine; 8-(4-chlorophenyl)H-imidazo[1,5-a]pyridine; 8-(2-methoxyphenyl)H-imidazo[1,5-a]pyridine; 8-(3-methoxyphenyl)H-imidazo[1,5-a]pyridine; 8-(4-methoxyphenyl)H-imidazo[1,5-a]pyridine; 8-(3-(benzyloxy)phenyl)H-imidazo[1,5-a]pyridine; 8-(biphen-3-yl)H-imidazo[1,5-a]pyridine; 8-(4-ethoxyphenyl)H-imidazo[1,5-a]pyridine; 8-(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)H-imidazo[1,5-a]pyridine; and 8-(3,4-dimethoxyphenyl)H-imidazo[1,5-a]pyridine; or a pharmaceutically acceptable salt of any one thereof. 12. A pharmaceutical composition comprising a compound according to claim 1 optionally in combination with one or more therapeutically acceptable diluents or carriers. 13. A pharmaceutical composition comprising a compound according to claim 10 optionally in combination with one or more therapeutically acceptable diluents or carriers. 14. The pharmaceutical composition of claim 12, further comprising at least one compound selected from the group consisting of neuroprotectants, antiparkinsonian drugs, amyloid protein deposition inhibitors, beta amyloid synthesis inhibitors, antidepressants, anxiolytic drugs, antipsychotic drugs and anti-multiple sclerosis drugs. 15. The pharmaceutical composition of claim 12, further comprising at least one compound selected from the group consisting of PEP-inhibitors, LiCl, inhibitors of inhibitors of DP IV or DP IV-like enzymes, acetylcholinesterase (ACE) inhibitors, PIMT enhancers, inhibitors of beta secretases, inhibitors of gamma secretases, inhibitors of neutral endopeptidase, inhibitors of Phosphodiesterase-4(PDE-4), TNFalpha inhibitors, muscarinic M1 receptor antagonists, NMDA receptor antagonists, sigma-1 receptor inhibitors, histamine H3 antagonists, immunomodulatory agents, immunosuppressive agents or an agent selected from the group consisting of antegren (natalizumab), Neurelan (fampridine-SR), campath (alemtuzumab), IR 208, NBI 5788/MSP 771 (tiplimotide), paclitaxel, Anergix.MS (AG 284), SH636, Differin (CD 271, adapalene), BAY 361677 (interleukin-4), matrix-metalloproteinase-inhibitors, interferon-tau (trophoblastin) and SAIK-MS. 16. A process for preparation of a compound of formula (I) according to claim 1, which comprises a ring closure reaction of a compound of formula (II) ##STR00046## wherein, the compound of formula (II) optionally further comprises a protecting group; the ring closure reaction comprises a suitable reagent in an organic solvent at reflux; R.sup.1 represents C.sub.2-8alkyl; C.sub.2-8alkenyl; --(C.sub.1-6alkyl)-aryl; --(C.sub.1-6alkyl)-heteroaryl; --(C.sub.1-6alkyl)-carbocyclyl; --(C.sub.1-6alkyl)-heterocyclyl; -aryl; -heteroaryl; -carbocyclyl or -heterocyclyl; wherein said aryl or heteroaryl groups may be optionally substituted by one or more substituents selected from, C.sub.1-4alkyl, C.sub.1-4fluoroalkyl, C.sub.1-4alkoxy, C.sub.1-4fluoroalkoxy, hydroxy, --SO.sub.2(C.sub.1-4alkyl), --SO.sub.2N(C.sub.1-4alkyl)(C.sub.1-4alkyl), SOC.sub.1-4alkyl, --SOC.sub.3-6cycloalkyl, --C(O)O(C.sub.1-4alkyl), benzyloxy and phenyl; and wherein said carbocyclyl and heterocyclyl groups may be optionally substituted by one or more substituents selected from --C.sub.1-4 alkyl, -C.sub.1-4 alkoxy, hydroxyl, halogen and oxo; R.sup.2 represents H; C.sub.1-4alkyl or halogen; R.sup.3 represents H; C.sub.1-4alkyl or halogen; and R.sup.4 represents H; C.sub.1-4alkyl or halogen. 17. A process according to claim 16, wherein the compound of formula (II) is obtained in situ by reacting a compound of formula (III) ##STR00047## wherein, the compound of formula (III) optionally further comprises a protecting group; and the compound of formula (II) is not isolated from the reaction mixture before reaction to the compound of formula (I). 18. A process according to claim 16, wherein the compound of formula (II) is obtained in situ by reacting a compound of formula (III) with methanoic acid or an activated derivative thereof; ##STR00048## wherein, the compound of formula (III) optionally further comprises a protecting group; and R.sup.1 represents C.sub.2-8alkyl; C.sub.2-8alkenyl; --(C.sub.1-6alkyl)-aryl; --(C.sub.1-6alkyl)-heteroaryl; --(C.sub.1-6alkyl)-carbocyclyl; --(C.sub.1-6alkyl)-heterocyclyl; -aryl; -heteroaryl; -carbocyclyl or -heterocyclyl; wherein said aryl or heteroaryl groups may be optionally substituted by one or more substituents selected from, C.sub.1-4alkyl, C.sub.1-4fluoroalkyl, C.sub.1-4alkoxy, C.sub.1-4fluoroalkoxy, hydroxy, --SO.sub.2(C.sub.1-4alkyl), --SO.sub.2N(C.sub.1-4alkyl)(C.sub.1-4alkyl), SOC.sub.1-4alkyl, --SOC.sub.3-6cycloalkyl, --C(O)O(C.sub.1-4alkyl), benzyloxy and phenyl; and wherein said carbocyclyl and heterocyclyl groups may be optionally substituted by one or more substituents selected from --C.sub.1-4 alkyl, -C.sub.1-4 alkoxy, hydroxyl, halogen and oxo; R.sup.2 represents H; C.sub.1-4alkyl or halogen; R.sup.3 represents H; C.sub.1-4alkyl or halogen; and R.sup.4 represents H; C.sub.l-4alkyl or halogen. 19. A process for preparation of a compound of formula (I) according to claim 1, in which R.sup.1 represents optionally substituted aryl or heteroaryl, which comprises: reacting a compound of formula (VII) ##STR00049## wherein R.sup.2 represents H; C.sub.1-4alkyl or halogen; R.sup.3 represents H; C.sub.1-4alkyl or halogen; R.sup.4 represents H; C.sub.1-4alkyl or halogen; and X represents a substituent selected from the group consisting of halogen or OTf; with a compound of formula (VIII), R.sup.1--Y (VIII) wherein R.sup.1 represents substituted aryl, substituted aryl, heteroaryl, or substituted heteroaryl and Y represents a boron or tin derivative.

Details for Patent 7,803,810

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Jubilant Hollisterstier Llc	N/A	positive skin test control-histamine	Injection	103891	03/13/1924		2028-03-09
Genzyme Corporation	CAMPATH	alemtuzumab	Injection	103948	05/07/2001		2028-03-09
Genzyme Corporation	LEMTRADA	alemtuzumab	Injection	103948	11/14/2014		2028-03-09
Genzyme Corporation	CAMPATH	alemtuzumab	Injection	103948	10/12/2004		2028-03-09
Biogen Inc.	TYSABRI	natalizumab	Injection	125104	11/23/2004		2028-03-09