A compound represented by formula (I), or a pharmaceutically acceptable salt, solvate, active metabolite, polymorph, isotope marker, isomer or prodrug thereof. Also provided are a pharmaceutical composition comprising the same, and the use of the compound and the pharmaceutical composition in the preparation of a medicament for treating tyrosine kinase-mediated diseases. The provided compound and the pharmaceutical composition thereof have significant tyrosine kinase inhibitory activity, can overcome tumor drug resistance, can break through the blood-brain barrier, and further have excellent pharmacokinetic properties and excellent oral bioavailability, and can be administered in a small dose, thereby reducing treatment cost for patients and possible side effects; therefore, the provided compound and the pharmaceutical composition thereof have great application potentials.

##STR00001##

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The disclosure features macrocyclic compounds, alone and in combination with other therapeutic agents, as well as pharmaceutical compositions and protein complexes thereof, capable of modulating biological processes including RAS and RAS-RAF inhibition, and their uses in the treatment of cancers.

The disclosure features macrocyclic compounds, alone and in combination with other therapeutic agents, as well as pharmaceutical compositions and protein complexes thereof, capable of modulating biological processes including RAS and RAS-RAF inhibition, and their uses in the treatment of cancers.

The disclosure relates to compounds that act as covalent inhibitors of epidermal growth factor receptor (EGFR); pharmaceutical compositions comprising the compounds; and methods of treating or preventing kinase-mediated disorders, including cancer and other proliferation diseases.

The disclosure relates to compounds that act as covalent inhibitors of epidermal growth factor receptor (EGFR); pharmaceutical compositions comprising the compounds; and methods of treating or preventing kinase-mediated disorders, including cancer and other proliferation diseases.

Provided are compounds of Formula I: ##STR00001## and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.

Provided are compounds of Formula I: ##STR00001## and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.

Provided are compounds of Formula I: ##STR00001## and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.

A compound, or a pharmaceutically acceptable salt or ester thereof, according to formula I:

R.sup.20-(Z).sub.b-(Y).sub.c(R.sup.21).sub.a(X).sub.dR.sup.22R.sup.23

wherein R.sup.20 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; Z is alkanediyl, substituted alkanediyl, cycloalkanediyl, or substituted cycloalkanediyl; Y is S, O, S(O), S(O)(O), or NR.sup.10, wherein R.sup.10 is H or alkyl; R.sup.21 is alkanediyl, substituted alkanediyl, cycloalkanediyl, substituted cycloalkanediyl, alkadienyl, substituted alkadienyl, cycloalkenediyl, substituted cycloalkenediyl, alkatrienyl, substituted alkatrienyl; X is C(O), S(O)(O), or N(H)C(O); R.sup.22 includes at least one divalent amino radical; R.sup.23 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; a, b, c, and d independently are 0 or 1.