The present disclosure relates to systems and methods for determining the renal glomerular filtration rate or assessing the renal function in a patient in need thereof. The system includes a computing device, a power supply, one or more sensors, and at least one tracer agent that fluoresces when exposed to electromagnetic radiation. The electromagnetic radiation is detected using the sensors, and the rate in which the fluorescence decreases in the patient is used to calculate the renal glomerular filtration rate in the patient.

Novel compounds that act as antagonists to human GPR39 protein are disclosed. Pharmaceutical compositions and methods of use for antagonists to human GPR39 protein are disclosed. In particular, methods of using the antagonists in the treatment of diseases or conditions including cardiovascular conditions, endocrine system and hormone disorders, cancer disorders, metabolic diseases, gastrointestinal and liver diseases, hematological disorders, neurological disorders and respiratory diseases are disclosed herein.

Novel compounds that act as antagonists to human GPR39 protein are disclosed. Pharmaceutical compositions and methods of use for antagonists to human GPR39 protein are disclosed. In particular, methods of using the antagonists in the treatment of diseases or conditions including cardiovascular conditions, endocrine system and hormone disorders, cancer disorders, metabolic diseases, gastrointestinal and liver diseases, hematological disorders, neurological disorders and respiratory diseases are disclosed herein.

An object of the present invention is to provide a compound useful as an anti-tumor agent or the like; an intermediate thereof; and a pharmaceutical composition, an anti-tumor agent, and a dihydroorotate dehydrogenase inhibitor, each of which contains the compound. According to the present invention, there is provided a compound represented by General Formula (1) or a salt thereof:

##STR00001## in the formula, Z.sup.1, Z.sup.2, and Z.sup.3 are the same as or different from each other and represent a nitrogen atom or CH; Z.sup.4 represents a nitrogen atom or a general formula of CR.sup.6; Z.sup.5 represents a nitrogen atom or a general formula of CR.sup.7 provided that at least one of Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4, or Z.sup.5 represents a nitrogen atom; R.sup.1 represents a general formula of CONHR.sup.8 or the like; R.sup.2 represents a C.sub.3-8 cycloalkyl group which may be substituted or the like; R.sup.3, R.sup.5, R.sup.6, and R.sup.7 are the same as or different from each other and represent a hydrogen atom, a halogen atom, or the like; R.sup.4 represents an aryl group which may be substituted or a heterocyclic group which may be substituted; R.sup.8 represents a general formula of SO.sub.2R.sup.9 or the like; and R.sup.9 represents an amino group which may be protected or the like.

The present invention relates to compounds of formula I:

##STR00001##

in which m, Y.sub.1, Y.sub.2, Y.sub.3, R.sub.1, R.sub.2a, R.sub.2b, R.sub.3a, R.sub.3b, R.sub.4a, R.sub.4b, R.sub.5a and R.sub.5b are defined in the Summary of the Invention; capable of inhibiting the activity of SHP2. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the management of diseases or disorders associated with the aberrant activity of SHP2.

The present invention relates to compounds of formula I:

##STR00001##

in which m, Y.sub.1, Y.sub.2, Y.sub.3, R.sub.1, R.sub.2a, R.sub.2b, R.sub.3a, R.sub.3b, R.sub.4a, R.sub.4b, R.sub.5a and R.sub.5b are defined in the Summary of the Invention; capable of inhibiting the activity of SHP2. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the management of diseases or disorders associated with the aberrant activity of SHP2.

The present invention relates to pyrazine derivatives such as those represented by Formulas I and II. X.sup.1 to X.sup.4 of Formulas I and II may be characterized as electron withdrawing groups, while Y.sup.1 to Y.sup.4 of Formulas I and II may be characterized as electron donating groups. Pyrazine derivatives of the present invention may be utilized in assessing organ (e.g., kidney) function. In a particular example, an effective amount of a pyrazine derivative that is capable of being renally cleared may be administered into a patient's body. The pyrazine derivative may capable of one or both absorbing and emanating spectral energy of at least about 400 nm (e.g., visible and/or infrared light). At least some of the derivative that is in the body may be exposed to spectral energy and, in turn, spectral energy may emanate from the derivative. This emanating spectral energy may be detected and utilized to determine renal function of the patient.

##STR00001##

The present invention relates to pyrazine derivatives such as those represented by Formulas I and II. X.sup.1 to X.sup.4 of Formulas I and II may be characterized as electron withdrawing groups, while Y.sup.1 to Y.sup.4 of Formulas I and II may be characterized as electron donating groups. Pyrazine derivatives of the present invention may be utilized in assessing organ (e.g., kidney) function. In a particular example, an effective amount of a pyrazine derivative that is capable of being renally cleared may be administered into a patient's body. The pyrazine derivative may capable of one or both absorbing and emanating spectral energy of at least about 400 nm (e.g., visible and/or infrared light). At least some of the derivative that is in the body may be exposed to spectral energy and, in turn, spectral energy may emanate from the derivative. This emanating spectral energy may be detected and utilized to determine renal function of the patient.

##STR00001##

The present invention relates to compounds of Formula (I), or a form thereof wherein ring A.sub.1, R.sub.1, R.sub.2, R.sub.3, R.sub.3′, L, W, and V are as defined herein, useful as FLAP modulators. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention. ##STR00001##

The present invention relates to compounds of Formula (I), or a form thereof wherein ring A.sub.1, R.sub.1, R.sub.2, R.sub.3, R.sub.3′, L, W, and V are as defined herein, useful as FLAP modulators. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention. ##STR00001##