Disclosed herein, inter alia, are inhibitors of alpha 2 beta 1 integrin and methods of using the same.

A compound, such as isoquinoline-6-sulfonyl chloride acid and/or addition salts thereof, may be useful as a manufacturing intermediate for an isoquinoline-6-sulfonamide compound. A method for manufacturing such compounds and/or or acid addition salts thereof, may involve subjecting 6-(benzylthio)isoquinoline to an oxidative chlorination reaction and/or reacting 6-aminoisoquinoline with a nitrite or nitrous acid ester, then with thionyl chloride, and then with an acid.

A compound, such as isoquinoline-6-sulfonyl chloride acid and/or addition salts thereof, may be useful as a manufacturing intermediate for an isoquinoline-6-sulfonamide compound. A method for manufacturing such compounds and/or or acid addition salts thereof, may involve subjecting 6-(benzylthio)isoquinoline to an oxidative chlorination reaction and/or reacting 6-aminoisoquinoline with a nitrite or nitrous acid ester, then with thionyl chloride, and then with an acid.

Disclosed are syntheses of a Cot (cancer Osaka thyroid) inhibitor, which has the following formula:

##STR00001##

Disclosed are syntheses of a Cot (cancer Osaka thyroid) inhibitor, which has the following formula:

##STR00001##

Methods are provided for modulating MRGPR X4 generally, or for treating a MRGPR X4 dependent condition more specifically, by contacting the MRGPR X4 or administering to a subject in need thereof, respectively, an effective amount of a compound having the structure of Formula (I):

##STR00001##

or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein n, x, A, Q.sub.1, Q.sub.2, Z, R, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined herein. Pharmaceutical compositions containing such compounds, as well as to compounds themselves, are also provided.

The present disclosure provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising these compounds thereof, and use of these compounds in preparing drugs for inhibiting ROCK. ##STR00001##

Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising these compounds thereof, and use of these compounds in preparing drugs for inhibiting ROCK. ##STR00001##

Provided herein are compounds and their pharmaceutically acceptable salts, lipid particles comprising such compounds or pharmaceutically acceptable salts thereof and compositions of the foregoing that can be used to reduce immune intolerance in a subject, for example, to treat autoimmune disorders, or in combination with an antigenic therapy, such as a protein or gene therapy, to improve the efficacy of the antigenic therapy. The compounds have the following structural formula:

##STR00001##

wherein values for the variables (e.g., Ring A, L, R.sup.1, R.sup.2, R.sup.3, m) are as described herein.