Claims for Patent: 9,006,430

Summary for Patent: 9,006,430

Title:	Ortho-condensed pyridine and pyrimidine derivatives (e.g., purines) as protein
Abstract:	The invention provides a compound for use as a protein kinase B inhibitor, the compound being a compound of the formula (I) or salts, solvates, tautomers or N-oxides thereof, wherein T is N or CR5; J1-J2 is N═C(R6), (R7)C═N, (R8)N—C(O), (R8)2C—C(O), N═N or (R7)C═C(R6); E is a monocyclic carbocyclic or heterocyclic group of 5 or 6 ring members, the heterocyclic group containing up to 3 heteroatoms selected from O, N and S; Q1 is a bond or a saturated C1-3 hydrocarbon linker group, one of the carbon atoms in the linker group being optionally be replaced by an oxygen or nitrogen atom, or an adjacent pair of carbon atoms may be replaced by CONRq or NRqCO where Rq is hydrogen or methyl, or Rq is a C1-4 alkylene chain linked to R or a carbon atom of Q1 to form a cyclic moiety; and wherein the carbon atoms of the linker group Q1 may optionally bear one or more substituents selected from fluorine and hydroxy; Q2 is a bond or a saturated hydrocarbon linker group containing from 1 to 3 carbon atoms, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group may optionally bear one or more substituents selected from fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the G group; and provided that when E is aryl or heteroaryl, then Q2 is other than a bond; G is hydrogen, NR2R3, OH or SH provided that when E is aryl or heteroaryl and Q2 is a bond, then G is hydrogen; R1 is hydrogen or an aryl or heteroaryl group, with the proviso that when R1 is hydrogen and G is NR2R3, then Q is a bond; and R2, R3, R4, R6 and R8 are as defined in the claims.
Inventor(s):	Valerio Berdini, Robert George Boyle, Gordon Saxty, David Winter Walker, Steven John Woodhead, Paul Graham Wyatt, Alastair Donald, John Caldwell, Ian Collins, Tatiana Faria Da Fonseca
Assignee:	Institute of Cancer Research, Cancer Research Technology Ltd, Astex Therapeutics Ltd
Application Number:	US14/310,475
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,006,430
Patent Claims:	1. A pharmaceutical composition comprising a compound of the formula (I): or a salt, tautomer or N-oxide thereof, wherein: T is N; J1-J2 is HC═CH; Q1 and Q2 each represent a bond; G is NR2R3; R1 is hydrogen; R2 and R3 are independently selected from hydrogen and methyl; R4 is hydrogen; and E is a piperidine group bearing 0-1 substituents R11 selected from the group R10 consisting of halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, mono-or di-C1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members; a group Ra-Rb wherein Ra is a bond, O, CO, X1C(X2), C(X2)X1, X1C(X2)X1, S, SO, SO2, NRc, SO2NRc or NRcSO2; and Rb is selected from hydrogen, carbocyclic and heterocyclic groups having from 3 to 12 ring members, and a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, carboxy, amino, mono- or di-C1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO2, NRc, X1C(X2), C(X2)X1 or X1C(X2)X1; Rc is selected from hydrogen and C1-4 hydrocarbyl; and X1 is O, S or NRc and X2 is ═O, ═S or ═NRc; provided that where the substituent group R10 comprises or includes a carbocyclic or heterocyclic group, the said carbocyclic or heterocyclic group may be unsubsituted or may itself be substituted with one or more further substituent groups R10 wherein (i) the said further substituent groups R10 include carbocyclic or heterocyclic groups, which are not themselves further substituted; or (ii) the said further substituent groups R10 do not include carbocyclic or heterocyclic groups but are otherwise selected from the groups listed above in the definition of R10; and a pharmaceutically acceptable carrier. 2. A pharmaceutical composition according to claim 1 wherein X1 is NRc and X2 is ═O. 3. A pharmaceutical composition according to claim 1 wherein NR2R3 is an amino group. 4. A pharmaceutical composition according to claim 1 wherein R11 is selected from the group R10b consisting of halogen, hydroxy, trifluoromethyl, cyano, amino, mono- or di-C1-4 alkylamino, cyclopropylamino, carbocyclic and heterocyclic groups having from 3 to 7 ring members; a group Ra-Rb wherein Ra is a bond, O, CO, OC(O), NRcC(O), OC(NRc), C(O)O, C(O)NRc, S, SO, SO2,NRc, SO2NRc or NRcSO2; and Rb is selected from hydrogen, carbocyclic and heterocyclic groups having from 3 to 7 ring members, and a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, amino, mono- or di-C1-4 alkylamino, carbocyclic and heterocyclic groups having from 3 to 7 ring members and wherein one or more carbon atoms of the C1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO2 or NRc; provided that Ra is not a bond when Rb is hydrogen; and Rc is selected from hydrogen and C1-4 alkyl. 5. A pharmaceutical composition according to claim 1 wherein the nitrogen atom of the piperidine ring is attached to the bicyclic group. 6. A pharmaceutical composition according to claim 1 wherein Q1 and Q2 are attached to different atoms in the group E. 7. A pharmaceutical composition according to claim 1 wherein Q2 and the bicyclic group are attached to the group E in a para relative orientation. 8. A pharmaceutical composition according to claim 1 wherein the compound of formula (I) is in the form of a salt or N-oxide. 9. A pharmaceutical composition according to claim 5 wherein R2 and R3 are hydrogen. 10. A pharmaceutical composition according to claim 9 wherein Q1 and Q2 are attached to different atoms in the group E. 11. A pharmaceutical composition according to claim 10 wherein X1 is NRc and X2 is ═O. 12. A pharmaceutical composition according to claim 11 wherein E is piperidine substituted with 1 substituent R11 selected from the group R10. 13. A pharmaceutical composition according to claim 12 wherein X1 is NRc and X2 is ═O. 14. A pharmaceutical composition according to claim 12, wherein the group R11 is selected from the group Ra-Rb. 15. A pharmaceutical composition according to claim 1 in a form suitable for oral or parenteral administration. 16. A pharmaceutical composition according to claim 1 in a form suitable for i.v. administration. 17. A pharmaceutical composition according to claim 1 further comprising one or more pharmaceutically acceptable adjuvants, excipients, diluents, fillers, buffers, stabilisers, preservatives, lubricants, and/or therapeutic or prophylactic agents. 18. A pharmaceutical composition according to claim 13 in a form suitable for oral or parenteral administration. 19. A pharmaceutical composition according to claim 13 in a form suitable for i.v. administration. 20. A pharmaceutical composition according to claim 13 further comprising one or more pharmaceutically acceptable adjuvants, excipients, diluents, fillers, buffers, stabilisers, preservatives, lubricants, and/or therapeutic or prophylactic agents.