Claims for Patent: 8,399,450
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Summary for Patent: 8,399,450
| Title: | Compounds and compositions as protein kinase inhibitors |
| Abstract: | The invention provides novel pyrimidine and pyridine derivatives and pharmaceutical compositions thereof, and methods for using such compounds. For example, the pyrimidine and pyridine derivatives of the invention may be used to treat, ameliorate or prevent a condition which responds to inhibition of anaplastic lymphoma kinase (ALK) activity, focal adhesion kinase (FAK), zeta-chain-associated protein kinase 70 (ZAP-70), insulin-like growth factor (IGF-1R), or a combination thereof. |
| Inventor(s): | Michellys; Pierre-Yves (San Marcos, CA), Pei; Wei (San Diego, CA), Marsilje; Thomas H. (San Diego, CA), Lu; Wenshuo (San Diego, CA), Chen; Bei (San Diego, CA), Uno; Tetsuo (San Diego, CA), Jin; Yunho (San Diego, CA), Jiang; Tao (San Diego, CA) |
| Assignee: | IRM LLC (Hamilton, BM) |
| Application Number: | 13/172,357 |
| Patent Claims: |
1. A compound having Formula (1): ##STR00363## or pharmaceutically acceptable salts thereof; wherein W is ##STR00364## A.sup.1 and A.sup.4 are independently C; each
A.sup.2 and A.sup.3 is C; B and C are independently an optionally substituted 5-7 membered carbocyclic ring, aryl, heteroaryl or heterocyclic ring containing N, O or S; Z.sup.1, Z.sup.2 and Z.sup.3 are independently NR.sup.11, C.dbd.O, CR--OR,
(CR.sub.2).sub.1-2 or .dbd.C--R.sup.12; R.sup.1 is halo or C.sub.1-6 alkyl; R.sup.2 is H; R.sup.3 is SO.sub.2R.sup.12 or cyano; R.sup.4, R.sup.7 and R.sup.10 are independently H; R, R.sup.5 and R.sup.5' are independently H or C.sub.1-6 alkyl;
R.sup.6 is --OR.sup.12; one of R.sup.8 and R.sup.9 is (CR.sub.2).sub.qY and the other is C.sub.1-6 alkyl; R.sup.11 is H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, (CR.sub.2).sub.pCO.sub.1-2R, (CR.sub.2).sub.pOR, (CR.sub.2).sub.pR.sup.13,
(CR.sub.2).sub.pNRR.sup.12, (CR.sub.2).sub.pCONRR.sup.12 or (CR.sub.2).sub.pSO.sub.1-2R.sup.12; R.sup.12 and R.sup.13 are independently an optionally substituted 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 5-7 membered
heterocyclic ring comprising N, O and/or S; aryl or heteroaryl; or R.sup.12 is H or C.sub.1-6 alkyl; Y is an optionally substituted 3-12 membered carbocyclic ring, a 5-12 membered aryl, or a 5-12 membered heteroaryl comprising N, O and/or S and
attached to A.sup.2 or A.sup.3 or both via a carbon atom of said heteroaryl n is 4; p is 0-4; and q is 0.
2. The compound of claim 1, wherein R.sup.12 is C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkenyl, pyrrolidinyl, piperazinyl, piperidinyl or morpholinyl. 3. The compound of claim 1, wherein R.sup.6 is --O(C.sub.1-6 alkyl). 4. The compound of claim 1, wherein R.sup.5 and R.sup.5' are H. 5. The compound of claim 1, wherein said compound is of Formula (2): ##STR00365## or pharmaceutically acceptable salts thereof; wherein R.sup.1 is halo or C.sub.1-6 alkyl; R.sup.2 is H; R.sup.6 is isopropoxy or methoxy; Y is an optionally substituted C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkenyl, or phenyl; or Y is pyridyl, pyrazolyl, isoxazolyl, imidazolyl, thiazolyl, or benzimidazolyl, each of which is attached to the phenyl ring via a carbon atom; and R.sup.3, R.sup.4, R.sup.8, R.sup.9 and n are as defined in claim 1. 6. The compound of claim 1, wherein said compound is of Formula (3A) or (3B): ##STR00366## wherein B and C together form ##STR00367## Z.sup.1, Z.sup.2 and Z.sup.3 together form ##STR00368## or tautomers thereof; R.sup.1 is halo or C.sub.1-6 alkyl; R.sup.2 is H; and R.sup.6 is isopropoxy or methoxy. 7. The compound of claim 6, wherein each R.sup.11 is (CR.sub.2).sub.pCO.sub.1-2R, (CR.sub.2).sub.pOR, (CR.sub.2).sub.pR.sup.13, (CR.sub.2).sub.pNRR.sup.12 or (CR.sub.2).sub.pCONRR.sup.12; R and R.sup.12 are independently H or C.sub.1-6 alkyl; and R.sup.13 is an optionally substituted piperidinyl, azetidiyl, tetrahydropyranyl, cyclohexyl, morpholinyl, pyrrolidinyl, heptamethyleneimine, octamethyleneimine, a bicyclic amine or diamine derivative, quinuclidin-3-yl, 8-methyl-8-aza-bicyclo[3.2.1]oct-6-yl], or 9-methyl-9-aza-bicyclo[4.2.1]nonan-7-yl. 8. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier. 9. A combination comprising a compound of claim 1, or pharmaceutically acceptable salts thereof, and a chemotherapeutic agent. 10. The compound of claim 1, wherein said compound is selected from the group consisting of ##STR00369## ##STR00370## ##STR00371## ##STR00372## ##STR00373## ##STR00374## ##STR00375## ##STR00376## ##STR00377## or a pharmaceutically acceptable salt thereof. 11. The compound of claim 5, wherein said compound is selected from the group consisting of ##STR00378## ##STR00379## ##STR00380## ##STR00381## ##STR00382## ##STR00383## ##STR00384## ##STR00385## ##STR00386## ##STR00387## ##STR00388## ##STR00389## ##STR00390## ##STR00391## or a pharmaceutically acceptable salt thereof. 12. The compound of claim 1, wherein said compound is selected from the group consisting of ##STR00392## ##STR00393## ##STR00394## ##STR00395## ##STR00396## ##STR00397## ##STR00398## ##STR00399## ##STR00400## ##STR00401## ##STR00402## ##STR00403## ##STR00404## ##STR00405## ##STR00406## ##STR00407## ##STR00408## ##STR00409## ##STR00410## ##STR00411## ##STR00412## ##STR00413## or pharmaceutically acceptable salts thereof. 13. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 10 and a pharmaceutically acceptable carrier. 14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 11 and a pharmaceutically acceptable carrier. 15. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 12 and a pharmaceutically acceptable carrier. |
