Claims for Patent: 9,512,082

Summary for Patent: 9,512,082

Title:	Inhibitors of glutaminyl cyclase
Abstract:	Compounds of formula (I), combinations and uses thereof for disease therapy, ##STR00001## or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof wherein: A represents ##STR00002## and B, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and Z are as defined throughout the description and the claims.
Inventor(s):	Buchholz; Mirko (Halle/Saale, DE), Heiser; Ulrich (Halle/Saale, DE), Niestroj; Andre J. (Sennewitz, DE)
Assignee:	PROBIODRUG AG (Halle (Saale), DE)
Application Number:	12/105,753
Patent Claims:	1. A compound of formula (I), ##STR00052## or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof wherein: (A) R.sup.1 represents (i) phenyl substituted by a monocyclic heteroaryl in which any of the phenyl and monocyclic heteroaryl groups may optionally be substituted by one or more substituents selected from C.sub.1-4alkyl, C.sub.1-4alkoxy-, and halogen; when A represents ##STR00053## or (B) R.sup.1 represents (i) phenyl substituted by one or more substituents selected from C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.1-6haloalkyl, --C.sub.1-6thioalkyl, --SO.sub.2C.sub.1-4alkyl, C.sub.1-6alkoxy-, --O--C.sub.3-8cycloalkyl, C.sub.3-8cycloalkyl, --SO.sub.2C.sub.3-8cycloalkyl, C.sub.3-6alkenyloxy-, C.sub.3-6alkynyloxy-, C(O)C.sub.1-6alkyl, C.sub.1-6alkoxy-C.sub.1-6alkyl-, nitro, cyano, hydroxyl, --C(O)OH, --NH.sub.2, --NHC.sub.1-4alkyl, --N(C.sub.1-4alkyl) (C.sub.1-4alkyl), --C(O)N(C.sub.1-4alkyl)(C.sub.1-4alkyl), --C(O)NH.sub.2, --C(O)NH(C.sub.1-4alkyl), --C(O)OC.sub.1-6alkyl, --SOC.sub.1-4alkyl, and --SOC.sub.3-6cycloalkyl; (ii) phenyl substituted by phenyl, or phenyl substitited by an optionally substituted monocyclic heteroaryl group in which any of the phenyl and monocyclic heteroaryl groups may optionally be substituted by one or more groups selected from C.sub.1-4alkyl, halogen, and C.sub.1-4alkoxy; or (iii) phenyl substituted by benzyloxy- in which either of the phenyl or benzyloxy- groups may optionally be substituted by one or more groups selected from C.sub.1-4alkyl, halogen, and C.sub.1-4alkoxy; when A represents ##STR00054## wherein Z represents a bond, --CH.sub.2--, --CH.sub.2--CH.sub.2--, --CH(Me)-, --CH(Me)-CH.sub.2- or --CH.sub.2--CH(Me)-; R.sup.5 and R.sup.6 independently represent H or C.sub.1-2alkyl; and B represents H or methyl. 2. A compound according to claim 1 wherein R.sup.1 represents (i) phenyl substituted by one or more groups selected from C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.1-6haloalkyl, --C.sub.1-6thioalkyl, --SO.sub.2C.sub.1-4alkyl, C.sub.1-6alkoxy-, --O--C.sub.3-8cycloalkyl, C.sub.3-8cycloalkyl, --SO.sub.2C.sub.3-8cycloalkyl, C.sub.3-6alkenyloxy-, C.sub.3-6alkynyloxy-, --C(O)C.sub.1-6alkyl, C.sub.1-6alkoxy-C.sub.1-6alkyl-, nitro, cyano, hydroxyl, --C(O)OH, --NH.sub.2, --NHC.sub.1-4alkyl, --N(C.sub.1-4alkyl)(C.sub.1-4alkyl), --C(O)N(C.sub.1-4alkyl)(C.sub.1-4alkyl), --C(O)NH.sub.2; and --C(O)NH(C.sub.1-4alkyl); or (ii) phenyl substituted by phenyl, or phenyl substituted by an optionally substituted monocyclic heteroaryl group in which any of the phenyl and monocyclic heteroaryl groups may optionally be substituted by one or more groups selected from C.sub.1-4alkyl, halogen, and C.sub.1-4alkoxy. 3. A compound according to claim 1 wherein R.sup.5 represents H; and R.sup.6 represents H. 4. A compound according to claim 1 wherein Z represents a bond, -CH.sub.2-, or -CH.sub.2-CH.sub.2--. 5. A compound according to claim 4 wherein Z represents a bond. 6. A compound according to claim 1 wherein B represents H. 7. A compound according to claim 1 selected from: 1-(3,4-dimethoxyphenyl)-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)urea; 1-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-(3-(5-methyl-1H-imidazol-1-yl)pr- opyl)urea; 1-(1H-benzo[d]imidazol-5-yl)-3-(3,4-dimethoxyphenyl)urea; and 1-((1H-benzo[d]imidazol-6-yl)methyl)-3-(3,4-dimethoxyphenyl)urea; or a pharmaceutically acceptable salt, tautomer, or stereoisomer of any one thereof. 8. A pharmaceutical composition comprising a compound according to claim 1 in combination with one or more therapeutically acceptable diluents or carriers. 9. The pharmaceutical composition of claim 8, which comprises additionally 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. 10. The pharmaceutical composition of claim 8, which comprises additionally at least one compound, selected from the group consisting of PEP-inhibitors, LiCI, 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. 11. A process for preparation of a compound of formula (I) wherein B represents H, according to claim 1, which comprises reaction of a compound of formula (XX) ##STR00055## wherein A is as defined in claim 1 with a compound of formula (XXI) R.sup.1--NH.sub.2 (XXI) wherein R.sup.1 is as defined in claim 1. 12. A compound according to claim 1 wherein R.sup.1 represents phenyl substituted by one or more substituents selected from C.sub.2-6haloalkyl and C.sub.2-6alkoxy--.

Details for Patent 9,512,082

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		2027-04-18
Genzyme Corporation	CAMPATH	alemtuzumab	Injection	103948	05/07/2001		2027-04-18
Genzyme Corporation	LEMTRADA	alemtuzumab	Injection	103948	11/14/2014		2027-04-18