Reactions that directly install nitrogen into CH bonds of complex molecules are significant because of their potential to change the chemical and biological properties of a given compound. Selective intramolecular CH amination reactions that achieve high levels of reactivity, while maintaining excellent site-selectivity and functional-group tolerance is a challenging problem. Herein is reported a manganese perchlorophthalocyanine catalyst [Mn.sup.III(ClPc)] for intermolecular benzylic CH amination of bioactive molecules and natural products that proceeds with unprecedented levels of reactivity and site-selectivity. In the presence of Brnsted or Lewis acid, the [Mn.sup.III(ClPc)]-catalyzed CH amination demonstrates unique tolerance for tertiary amine, pyridine and benzimidazole functionalities. Mechanistic studies indicate that CH amination proceeds through an electrophilic metallonitrene intermediate via a stepwise pathway where CH cleavage is the rate-determining step of the reaction. Collectively these mechanistic features contrast previous base-metal catalyzed CH aminations.

Reactions that directly install nitrogen into CH bonds of complex molecules are significant because of their potential to change the chemical and biological properties of a given compound. Selective intramolecular CH amination reactions that achieve high levels of reactivity, while maintaining excellent site-selectivity and functional-group tolerance is a challenging problem. Herein is reported a manganese perchlorophthalocyanine catalyst [Mn.sup.III(ClPc)] for intermolecular benzylic CH amination of bioactive molecules and natural products that proceeds with unprecedented levels of reactivity and site-selectivity. In the presence of Brnsted or Lewis acid, the [Mn.sup.III(ClPc)]-catalyzed CH amination demonstrates unique tolerance for tertiary amine, pyridine and benzimidazole functionalities. Mechanistic studies indicate that CH amination proceeds through an electrophilic metallonitrene intermediate via a stepwise pathway where CH cleavage is the rate-determining step of the reaction. Collectively these mechanistic features contrast previous base-metal catalyzed CH aminations.

The invention is directed to a class of compounds, including the pharmaceutically acceptable salts of the compounds, having the structure of formula I:

##STR00001##

as defined in the specification. The invention is also directed to compositions containing and uses of the compounds of formula I.

The invention is directed to a class of compounds, including the pharmaceutically acceptable salts of the compounds, having the structure of formula I:

##STR00001##

as defined in the specification. The invention is also directed to compositions containing and uses of the compounds of formula I.

The present invention provides for novel compounds of Formula (I) and pharmaceutically acceptable salts and co-crystals thereof which have glucagon receptor antagonist or inverse agonist activity. The present invention further provides for pharmaceutical compositions comprising the same as well as methods of treating, preventing, delaying the time to onset or reducing the risk for the development or progression of a disease or condition for which one or more glucagon receptor antagonist is indicated, including Type I and II diabetes, insulin resistance and hyperglycemia. The present invention also provides for processes of making the compounds of Formula I, including salts and co-crystals thereof, and pharmaceutical compositions comprising the same.

The present invention provides for novel compounds of Formula (I) and pharmaceutically acceptable salts and co-crystals thereof which have glucagon receptor antagonist or inverse agonist activity. The present invention further provides for pharmaceutical compositions comprising the same as well as methods of treating, preventing, delaying the time to onset or reducing the risk for the development or progression of a disease or condition for which one or more glucagon receptor antagonist is indicated, including Type I and II diabetes, insulin resistance and hyperglycemia. The present invention also provides for processes of making the compounds of Formula I, including salts and co-crystals thereof, and pharmaceutical compositions comprising the same.

The present disclosure provides, for example, a method of stabilizing the RAF/MEK complex in a subject, the method comprising administering to the subject an effective amount of a compound represented by the general formula below or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of the compound or salt:

##STR00001##

wherein X.sub.1, X.sub.2, X.sub.3 and X.sub.4 are each independently CR.sub.2? or N?, R.sub.2 is, for example, a halogen atom, R.sub.1 is, for example, S(?O).sub.2NHR.sub.8, R.sub.8 is, for example, a C1-6 alkyl group, R.sub.3 is, for example, a hydrogen atom, R.sub.5 is, for example, a halogen atom, R.sub.6 is, for example, a hydrogen atom, and R.sub.4 is, for example, a cyclopropyl group.

The present disclosure provides, for example, a method of stabilizing the RAF/MEK complex in a subject, the method comprising administering to the subject an effective amount of a compound represented by the general formula below or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of the compound or salt:

##STR00001##

wherein X.sub.1, X.sub.2, X.sub.3 and X.sub.4 are each independently CR.sub.2? or N?, R.sub.2 is, for example, a halogen atom, R.sub.1 is, for example, S(?O).sub.2NHR.sub.8, R.sub.8 is, for example, a C1-6 alkyl group, R.sub.3 is, for example, a hydrogen atom, R.sub.5 is, for example, a halogen atom, R.sub.6 is, for example, a hydrogen atom, and R.sub.4 is, for example, a cyclopropyl group.

Described herein are compounds, pharmaceutical compositions and medicaments that include such compounds, and methods of using such compounds to modulate transient receptor potential vanilloid 1 receptor (TRPV1) activity.

Described herein are compounds, pharmaceutical compositions and medicaments that include such compounds, and methods of using such compounds to modulate transient receptor potential vanilloid 1 receptor (TRPV1) activity.