The present invention relates to a novel compound as protein kinase inhibitors.

The present invention relates to a novel compound as protein kinase inhibitors.

The present invention relates to a pyrimidine-2,4-diamine derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition for prevention or treatment of cancer comprising the same as an effective ingredient. A compound according to the present invention has the good effect of inhibiting anaplastic lymphoma kinase (ALK) activity, whereby a therapeutic effect on cancer cells having an anaplastic lymphoma kinase (ALK) fusion protein such as EML4-ALK, NPM-ALK, etc. can be enhanced and it is expected that a recurrence of cancer will be effectively inhibited. As such, the compound can be effectively used in a pharmaceutical composition for prevention or treatment of cancer.

The present invention relates to a pyrimidine-2,4-diamine derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition for prevention or treatment of cancer comprising the same as an effective ingredient. A compound according to the present invention has the good effect of inhibiting anaplastic lymphoma kinase (ALK) activity, whereby a therapeutic effect on cancer cells having an anaplastic lymphoma kinase (ALK) fusion protein such as EML4-ALK, NPM-ALK, etc. can be enhanced and it is expected that a recurrence of cancer will be effectively inhibited. As such, the compound can be effectively used in a pharmaceutical composition for prevention or treatment of cancer.

A compound of formula (Ic) ##STR00001## wherein X.sup.2 represents a CONR.sub.k group, wherein R.sub.k represents a hydrogen atom or a methyl group, a NHCONH group, a OCH.sub.2 group, a CH(OH) group, a NHCO group, a O group, a O(CH.sub.2).sub.sO, a CO group, a SO.sub.2 group, a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms, a NHSO.sub.2 or a SO.sub.2NH group; Y.sup.2 represents a hydrogen atom, a halogen atom, a hydroxyl group, a (C.sub.1-C.sub.4)alkoxy group, a ##STR00002##
a ##STR00003##
group, a ##STR00004##
group, a morpholinyl group, optionally substituted by a (C.sub.1-C.sub.4)alkyl group, a piperazinyl group, a piperidinyl group, or a CR.sup.1R.sup.2R.sup.3 group, or any of its pharmaceutically acceptable salt.

Disclosed herein are, inter alia, compounds modulating Inositol-Requiring Enzyme 1 (IRE1) and IRE1 activity and methods of use thereof for treating IRE1-mediated and IRE1-mediated disorders.

A compound of formula (Ie): ##STR00001##
wherein Y.sup.1 represents an aryl group, X.sup.2 represents a O group, a NH group, a S group, a CONH group, a NHCONH group, a NHCO group, a CH(OH) group, a CH(COOH)NH group, a CH(COOCH.sub.3)NH group, a C(OH)(CH.sub.2OH), a ##STR00002##
group, a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or heteroatoms, a SO.sub.2 group, or a SO.sub.2NH group, Y.sup.2 represents a hydrogen atom, a hydroxyl group, a (C.sub.1-C.sub.4)alkoxy group, a CHC(OH).sub.2, a COOR.sub.f, wherein R.sub.f represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, a morpholinyl group, a dihydropyranyl group, a ##STR00003##
group, a ##STR00004##
group, a PO(OR.sub.f)(OR.sub.f) group, wherein R.sub.f and R.sub.f independently represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, an oxetanyl group, a Si(CH.sub.3).sub.3 group, a NHCOO(C.sub.1-C.sub.4)alkyl group, or a CR.sup.1R.sup.2R.sup.3 group, or any of its pharmaceutically acceptable salt and pharmaceutical compositions containing them and to synthesis process for manufacturing them.