Pyrazines and Pyridines and Derivatives Thereof as Therapeutic Compounds

The present invention pertains to certain pyrazines and pyridines, and derivatives thereof, which, inter alia, inhibit RAF (e.g., B RAF) activity, inhibit cell proliferation, treat cancer, etc., and more particularly to compounds of the formulae: (I) wherein: Q is independently -N- or -CH-; one of R...

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Hauptverfasser: VELA ESTEBAN R, MARAIS RICHARD M, TAYLOR RICHARD D, GILL ADRIAN L, SPRINGER CAROLINE J, NICULESCU-DUVAZ ION
Format: Patent
Sprache:eng
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Zusammenfassung:The present invention pertains to certain pyrazines and pyridines, and derivatives thereof, which, inter alia, inhibit RAF (e.g., B RAF) activity, inhibit cell proliferation, treat cancer, etc., and more particularly to compounds of the formulae: (I) wherein: Q is independently -N- or -CH-; one of RP2 and RP3 is independently a group of the formula -J1-L1-Z; wherein: if Q is -N-, then -J1-L1-Z is independently: -NH-Z; -O-Z; or S-Z; if Q is -CH-, then -J1-L1-Z is independently: -NH-(CH2)n-Z, wherein n is independently 0 or 1; -O-Z; or -S-Z; Z is independently: C6-14 carboaryl, C5-14 heteroaryl, C3-12carbocyclic, C3-12 heterocyclic; and is independently unsubstituted or substituted; the other of RP2 and RP3 is independently -H, -NHRN1, or -NHC(-O)RN2; wherein: RN1, if present, is independently -H or aliphatic saturated C1-4alkyl; RN2, if present, is independently -H or aliphatic saturated C1-4alkyl; one of RP5 and RP6 is independently a group of the formula -W-Y; wherein: W is independently: a covalent bond; -NRN4-, -O-, -S-, -C(-O)-, -CH2-; -NRN4-CH2-, -O-CH2-, -S-CH2-, -C(-O)-CH2-, -(CH2)2-; -CH2-NRN4-, -CH2-O-, -CH2-S-, or -CH2-C(-O)-; wherein RN4, if present, is independently -H or aliphatic saturated C1-4alkyl; Y is independently: C6-14carboaryl, C5-14heteroaryl, C3-12carbocyclic, C3-12heterocyclic; and is independently unsubstituted or substituted; the other of RP5 and RP6 is independently -H; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, e.g., both in vitro and in vivo, to inhibit RAF (e.g., B-RAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and conditions that are ameliorated by the inhibition of RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.