We report the design of a catalytic, bifunctional template that binds heterocyclic substrate via reversible coordination instead of covalent linkage, allowing remote site-selective CH olefination of heterocycles. The two metal centers coordinated to this template play different roles; anchoring substrates to the proximity of catalyst and cleaving the remote CH bonds respectively. Using this strategy, we demonstrate remote site-selective CH olefination of heterocyclic substrates which do not have functional group handles for covalently attaching templates. For instance the olefination can be an alkenylation of a 3-phenylpyridine with an acrylate alkyl ester selective for the meta position of the phenyl group with respect to the pyridine, or can be an alkenylation of a quinoline with an acrylate alkyl ester selective for the 5-position of the quinoline.

The present disclosure discloses a biaryl urea RORt inhibitor, and specifically relates to a biaryl urea derivative, as represented by formula I, with an RORt inhibiting activity, and a preparation process thereof, and a pharmaceutical composition comprising the compound. Further disclosed is use of the compound for treating an RORt-related disease. ##STR00001##

The present disclosure discloses a biaryl urea RORt inhibitor, and specifically relates to a biaryl urea derivative, as represented by formula I, with an RORt inhibiting activity, and a preparation process thereof, and a pharmaceutical composition comprising the compound. Further disclosed is use of the compound for treating an RORt-related disease. ##STR00001##

The invention discloses compounds of Formula (I), ##STR00001##
wherein A.sup.1, R.sup.1, R.sup.2, R.sup.3, R.sup.4, and n are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.

The invention discloses compounds of Formula (I), ##STR00001##
wherein A.sup.1, R.sup.1, R.sup.2, R.sup.3, R.sup.4, and n are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.

The invention discloses compounds of Formula (I), ##STR00001##
wherein A.sup.1, R.sup.1, R.sup.2, R.sup.3, R.sup.4, and n are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.

The invention discloses compounds of Formula (I), ##STR00001##
wherein A.sup.1, R.sup.1, R.sup.2, R.sup.3, R.sup.4, and n are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.

The new arylsulfonamide and arylsulfone derivatives are modulators of TRPML and are useful in treating disorders related to TRPML activities and lysosome functions such as acid-related disorders and cancer.

The invention discloses compounds of Formula (I), ##STR00001##
wherein A.sup.1, R.sup.1, R.sup.2, R.sup.3, R.sup.4, and n are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.

The invention discloses compounds of Formula (I), ##STR00001##
wherein A.sup.1, R.sup.1, R.sup.2, R.sup.3, R.sup.4, and n are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.