Provided herein, inter alia, are methods and compounds for modulating K-Ras treating cancer.

##STR00001##

A cooling agent composition includes a methyl menthol derivative represented by the following general formula (1). In the formula (1), a symbol * indicates an asymmetric carbon atom, X represents a hydrogen atom or a substituent, and Y represents an aryl group having 6 to 20 carbon atoms which may have a substituent.

##STR00001##

A cooling agent composition includes a methyl menthol derivative represented by the following general formula (1). In the formula (1), a symbol * indicates an asymmetric carbon atom, X represents a hydrogen atom or a substituent, and Y represents an aryl group having 6 to 20 carbon atoms which may have a substituent.

##STR00001##

Methods and compositions for improved plant breeding using gene editing and haploid induction are provided.

RhlR modulators including agonist and antagonists which are useful for modulating QS phenotypes in Gram-negative bacteria. Certain compounds of general formula A-W-HG having various carbocyclic ad heterocyclic head groups (HG) and various tail groups (A), where W is CONH, SO.sub.2NH, CONHCH.sub.2, or SO.sub.2NHCH.sub.2 are RhlR agonists or antagonists. The compounds are useful in methods of modulating quorum sensing in Gram-negative bacteria, particularly in Pseudomonas. Compositions including certain RhlR modulators are useful for decreasing the virulence of Gram-negative bacteria. Pharmaceutical compositions comprising certain RhlR modulators are useful for treatment of infections of Gram-negative bacteria.

RhlR modulators including agonist and antagonists which are useful for modulating QS phenotypes in Gram-negative bacteria. Certain compounds of general formula A-W-HG having various carbocyclic ad heterocyclic head groups (HG) and various tail groups (A), where W is CONH, SO.sub.2NH, CONHCH.sub.2, or SO.sub.2NHCH.sub.2 are RhlR agonists or antagonists. The compounds are useful in methods of modulating quorum sensing in Gram-negative bacteria, particularly in Pseudomonas. Compositions including certain RhlR modulators are useful for decreasing the virulence of Gram-negative bacteria. Pharmaceutical compositions comprising certain RhlR modulators are useful for treatment of infections of Gram-negative bacteria.

Disclosed are compounds of Formula (I) or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof, wherein Q is a 5-membered heterocyclyl or 5-membered heteroaryl having 1 to 4 heteroatoms independently selected from N, O, and S, substituted with zero to 4 R.sup.1; and A, X.sup.1, X.sup.2, X.sup.3, X.sup.4, Z.sup.1, Z.sup.2, R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, a, b, and d are defined herein. Also disclosed are methods of using these compounds to modulate the activity of farnesoid X receptor (FXR); pharmaceutical compositions comprising these compounds; and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions. ##STR00001##

Disclosed are compounds of Formula (I) or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof, wherein Q is a 5-membered heterocyclyl or 5-membered heteroaryl having 1 to 4 heteroatoms independently selected from N, O, and S, substituted with zero to 4 R.sup.1; and A, X.sup.1, X.sup.2, X.sup.3, X.sup.4, Z.sup.1, Z.sup.2, R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, a, b, and d are defined herein. Also disclosed are methods of using these compounds to modulate the activity of farnesoid X receptor (FXR); pharmaceutical compositions comprising these compounds; and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions. ##STR00001##

Compounds of formula (I) can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX). ##STR00001##

Disclosed is a process for the preparation of certain intermediates, e.g. those in the scheme below: which intermediates and processes are useful in the preparation of the macrocyclic HVC inhibitor Simeprevir.

##STR00001##