Embodiments of the present invention generally concern pharmaceutical formulations and compositions and methods for using the pharmaceutical formulations and compositions which comprise derivatives of benzimidazole compounds, their racemic mixtures, their enantiomers, their complexes, their salts, and combinations thereof which have been found to be novel agonists of imidizoline receptors with surprising life extending efficacies due to their geroprotective (anti-geriatric) actions on pathologies associated with the aging processes in humans and animals.

Provided are a labelling agent including a compound of the following Formula 1, a labelling composition, a method of labelling a protein with the labelling agent, and a method of detecting the protein using the labelling agent: ##STR00001##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.8 are independently H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, R.sub.7 is H or —NR.sub.9R.sub.10, R.sub.9 and R.sub.10 are independently H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, X is —NR.sub.11, —O, or S, R.sub.11 is H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, Y is —OR.sub.12 or —NR.sub.13R.sub.14, R.sub.12 is H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, and R.sub.13 and R.sub.14 are independently H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl.

Provided are a labelling agent including a compound of the following Formula 1, a labelling composition, a method of labelling a protein with the labelling agent, and a method of detecting the protein using the labelling agent: ##STR00001##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.8 are independently H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, R.sub.7 is H or —NR.sub.9R.sub.10, R.sub.9 and R.sub.10 are independently H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, X is —NR.sub.11, —O, or S, R.sub.11 is H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, Y is —OR.sub.12 or —NR.sub.13R.sub.14, R.sub.12 is H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl, and R.sub.13 and R.sub.14 are independently H, substituted or unsubstituted —C.sub.1-10-alkyl-, —C.sub.2-10-alkenyl, or —C.sub.2-10-alkynyl.

Deuterated domperidone compositions, methods of synthesis, methods of use, and dosing formulations providing beneficial safety and other effects.

The present invention provides compounds of formula (IV); ##STR00001##
or pharmaceutically acceptable salts thereof, wherein the variables are defined as herein. The present invention provides a method for manufacturing the compounds of formula (IV), their therapeutic uses, combinations with other of pharmacologically active agents, and a pharmaceutical compositions.

The present invention provides compounds of formula (IV); ##STR00001##
or pharmaceutically acceptable salts thereof, wherein the variables are defined as herein. The present invention provides a method for manufacturing the compounds of formula (IV), their therapeutic uses, combinations with other of pharmacologically active agents, and a pharmaceutical compositions.

The present invention provides a novel heterocyclic derivative or a pharmaceutically acceptable salt thereof. For example, the present invention provides a heterocyclic derivative of the general formula [1] or its tautomer, or a pharmaceutically acceptable salt thereof: ##STR00001##
wherein R.sup.1 and R.sup.2 are the same or different aromatic rings, etc., and ring A is a heterocyclic ring. The compound of the invention or a pharmaceutically acceptable salt thereof has potent mPGES-1 inhibiting activity and is useful as an agent for the treatment or prevention of a disease, such as rheumatoid arthritis, osteoarthritis, temporomandibular joint disorders, low back pain, endometriosis, dysmenorrhea, overactive bladder, malignant tumors or neurodegenerative disease.

The present invention provides a novel heterocyclic derivative or a pharmaceutically acceptable salt thereof. For example, the present invention provides a heterocyclic derivative of the general formula [1] or its tautomer, or a pharmaceutically acceptable salt thereof: ##STR00001##
wherein R.sup.1 and R.sup.2 are the same or different aromatic rings, etc., and ring A is a heterocyclic ring. The compound of the invention or a pharmaceutically acceptable salt thereof has potent mPGES-1 inhibiting activity and is useful as an agent for the treatment or prevention of a disease, such as rheumatoid arthritis, osteoarthritis, temporomandibular joint disorders, low back pain, endometriosis, dysmenorrhea, overactive bladder, malignant tumors or neurodegenerative disease.

The invention relates to compounds of formula I, or a pharmaceutically-acceptable salt thereof. The present invention also relates to pharmaceutical formulations comprising these compounds, and to their use as medicaments for the treatment of disorders where modulation of DCTPP (deoxycytidine triphosphate pyrophosphatase 1) activity exerts a therapeutic effect.

##STR00001##

The invention relates to compounds of formula I, or a pharmaceutically-acceptable salt thereof. The present invention also relates to pharmaceutical formulations comprising these compounds, and to their use as medicaments for the treatment of disorders where modulation of DCTPP (deoxycytidine triphosphate pyrophosphatase 1) activity exerts a therapeutic effect.

##STR00001##