The present invention relates to compounds that inhibit at least one of KRas G12A, KRas G12C, KRas G12D, KRas G12R, KRas G12S, KRas G12V, KRas G13D and KRas Q61H, pharmaceutical compositions comprising the compounds and methods of use therefor.

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, 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, 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, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; a, b, c, and d independently are 0 or 1.

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, 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, 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, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; a, b, c, and d independently are 0 or 1.

The present invention directs to a compound represented by formula (I).

The present invention directs to a compound represented by formula (I).

Compounds, such as cathinone derivatives, and pharmaceutical formulations that include the compounds. The compounds may have a first selectivity for a first receptor subtype that is at least 10 times greater than a second selectivity for a second receptor subtype from the same class of receptors. Methods of treating patients, which may include administering to a patient a pharmaceutical formulation that includes a compound, such as a cathinone derivative.

The present invention relates to compounds of formula (I): ##STR00001##
for use as peripheral NMDA receptor antagonists.

The present invention relates to compounds of formula (I): ##STR00001##
for use as peripheral NMDA receptor antagonists.

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.