Claims for Patent: 8,633,201

Summary for Patent: 8,633,201

Title:	Thienopyrimidines having Mnk1/Mnk2 inhibiting activity for pharmaceutical compositions
Abstract:	The present invention relates to novel pharmaceutical compositions comprising thienopyrimidine compounds. Moreover, the present invention relates to the use of the thienopyrimidine compounds of the invention for the production of pharmaceutical compositions for the prophylaxis and/or treatment of diseases which can be influenced by the inhibition of the kinase activity of Mnk1 and/or Mnk2 (Mnk2a or Mnk2b) and/or variants thereof.
Inventor(s):	Aicher; Babette (Frankfurt am Main, DE), Coulter; Thomas Stephen (Wantage, GB), Jaekel; Stefan (Darmstadt, DE), Kelter; Arndt-Rene (Alfter, DE), Murfin; Stephen (Didcot, GB), Reuter; Tanja (Darmstadt, DE), Taylor; Steven (Didcot, GB)
Assignee:	Boehringer Ingelheim International GmbH (Ingelheim am Rhein, DE)
Application Number:	12/296,427
Patent Claims:	1. A compound of the formula (1) ##STR00027## wherein X is O; R.sub.1 is C.sub.3-6alkyl optionally substituted with one or more halogen atoms, C.sub.3-10 cycloalkyl, or 3 to 10 membered heterocycloalkyl comprising a heteroatom selected from N and O and, optionally substituted with one or more R.sub.9; R.sub.2 and R.sub.3 are the same or different and are independently selected from hydrogen and C.sub.1-6 alkyl; R.sub.4 is hydrogen, C.sub.1-4 alkyl, urea, thiourea or acetyl optionally substituted with one or more R.sub.9; R.sub.5, R.sub.7 and R.sub.8 are hydrogen; R.sub.6 is selected from, halogen, --C(O)N(R.sub.11R.sub.11a) and --COOR.sub.11; R.sub.9 is independently halogen; CN; COOR.sub.11; OR.sub.11; C(O)N(R.sub.11R.sub.11a); S(O).sub.2N(R.sub.11R.sub.11a); S(O)N(R.sub.1 1R.sub.11a); S(O).sub.2R.sub.11; N(R.sub.11)S(O).sub.2N(R.sub.11aR.sub.11b); SR.sub.11; N(R.sub.11R.sub.11a); OC(O)R.sub.11; N(R.sub.11)C(O)R.sub.11a; N(R.sub.11)S(O)R.sub.11a; N(R.sub.11)S(O)R.sub.11a; N(R.sub.11)C(O)N(R.sub.11aR.sub.11b); N(R.sub.11)C(O)OR.sub.11a; OC(O)N(R.sub.11R.sub.11a); oxo (.dbd.O); C(O)R.sub.11; C.sub.11b alkyl; phenyl; C.sub.3-7 cycloalkyl; or 5 or 6 membered saturated, unsaturated or aromatic heterocyclyl comprising at least one heteroatom selected from N, S and O; wherein C.sub.1-6 alkyl, phenyl, C.sub.3-7 cycloalkyl, and heterocyclyl are optionally substituted with one or more R.sub.10; R.sub.10 is independently halogen; CN; OR.sub.11; S(O).sub.2N(R.sub.11R.sub.11a); S(O)N(R.sub.11R.sub.11a); S(O).sub.2R.sub.11; N(R.sub.11)S(O).sub.2N(R.sub.11aR.sub.11b); SR.sub.11; N(R.sub.11R.sub.11a); OC(O)R.sub.11; N(R.sub.11)C(O)R.sub.11a; N(R.sub.11)S(O).sub.2R.sub.11a; N(R.sub.11)S(O)R.sub.11a; N(R.sub.11)C(O)N(R.sub.11aR.sub.11b); N(R.sub.11)C(O)OR.sub.11a; OC(O)N(R.sub.11R.sub.11a); oxo (.dbd.O); C(O)R.sub.11; C.sub.1-6 alkyl; phenyl; C.sub.3-7 cycloalkyl; or heterocyclyl; R.sub.11, R.sub.11a, R.sub.11b are independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkyl C.sub.3-10 cycloalkyl, C.sub.3-10 cycloalkyl, C.sub.1-6 alkyl 3 to 10 membered heterocycloalkyl comprising at least one heteroatom selected from N, S and O, 3 to 10 membered heterocycloalkyl comprising at least one heteroatom selected from N, S and O, C.sub.6-10 aryl, 5 to 10 membered heteroaryl comprising at least one heteroatom selected from N, S and O; or a pharmaceutically acceptable salt thereof. 2. The compound according to claim 1, wherein R.sub.2 and R.sub.3 are hydrogen. 3. The compound according to claim 1, wherein R.sub.4 is hydrogen. 4. The compound according to claim 1, wherein R.sub.6 is selected from fluorine, COOH and C(O)NH.sub.2. 5. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. 6. The pharmaceutical composition according to claim 5 further comprising an additional therapeutic agent. 7. The pharmaceutical composition according to claim 6 wherein the additional therapeutic agent is selected from an antidiabetic agent, a lipid lowering agent, a cardiovascular agent, an antihypertensive agent, a diuretic agent, a thrombocyte aggregation inhibitor, an antineoplastic agent or an anti-obesity agent. 8. The pharmaceutical composition according to claim 6, wherein the additional therapeutic agent is selected from human NPH insulin, human lente or ultralente insulin, insulin Lispro, insulin Aspatart, or insulin Glargine, atenolol, bisoprolol, metoprolol, esmolol, celiprolol, talinolol, oxprenolol, pindolol, propanolol, bupropanolol, penbutolol, mepindolol, sotalol, certeolol, nadolol, carvedilol, nifedipin, nitrendipin, amlodipin, nicardipin, nisoldipin, diltiazem, enalapril, verapamil, gallopamil, quinapril, captopril, lisinopril, benazepril, ramipril, peridopril, fosinopril, trandolapril, irbesatan, losartan, valsartan, telmisartan, eprosartan, olmesartan, hydrochlorothiazide, piretanid, chlorotalidone, mefruside, furosemide, bendroflumethiazid, triamterene, dehydralazine, acetylsalicylic acid, tirofiban-HCl, dipyramidol, triclopidin, iloprost-trometanol, eptifibatide, clopidogrel, piratecam, abciximab, trapidil, simvastatine, bezafibrate, fenofibrate, gemfibrozil, etofyllin, clofibrate, etofibrate, fluvastatine, lovastatine, pravastatin, colestyramide, colestipol-HCl, xantinol nicotinat, inositol nicotinate, acipimox, nebivolol, glycerolnitrate, isosorbide mononitrate, isosorbide dinitrate, pentaerythrityl tetranitrate, indapamide, cilazepril, urapidil, eprosartan, nilvadipin, metoprolol, doxazosin, molsidormin, moxaverin, acebutolol, prazosine, trapidil, clonidine, vinblastin, vincristin, vindesin, vinorelbin, podophyllotoxine derivatives, etoposid, teniposid, alkylating agents, nitroso ureas, cycloplonphamid, estamustin, melphalan, ifosfamid, mitoxantron, idarubicin, doxorubicin, bleomycin, mitomycin, dactinomycin, daptomycin, cytarabin, fluorouracil, fluoroarabin, gemcitabin, tioguanin, capecitabin, adriamydin/daunorubicin, cytosine arabinosid/cytarabine, 4-HC, and other phosphamides. 9. The pharmaceutical composition according to claim 5, wherein the pharmaceutically acceptable carrier is adapted for oral, parenteral, local, or topical administration. 10. The compound according to claim 1 selected from: ##STR00028## ##STR00029## ##STR00030## ##STR00031## ##STR00032## 11. The compound according to claim 1 selected from the group consisting of ##STR00033## ##STR00034## ##STR00035## 12. The compound according to claim 1 represented by the following formula: ##STR00036##

Details for Patent 8,633,201

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	HUMULIN R U-100	insulin human	Injection	018780	10/28/1982		2026-04-07
Eli Lilly And Company	HUMULIN R U-500	insulin human	Injection	018780	12/29/2015		2026-04-07
Eli Lilly And Company	HUMULIN R U-100	insulin human	Injection	018780	08/06/1998		2026-04-07
Eli Lilly And Company	HUMULIN R U-500	insulin human	Injection	018780	03/31/1994		2026-04-07
Eli Lilly And Company	HUMULIN R U-100	insulin human	Injection	018780	05/25/2018		2026-04-07
Sanofi-aventis U.s. Llc	LANTUS	insulin glargine	Injection	021081	04/20/2000		2026-04-07