A61K31/5386

TRICYCLIC PI3K INHIBITOR COMPOUNDS AND METHODS OF USE

Tricyclic PI3k inhibitor compounds of Formula I with anti-cancer activity, anti-inflammatory activity, or immunoregulatory properties, and more specifically with PI3 kinase modulating or inhibitory activity are described. Methods are described for using the tricyclic PI3K inhibitor compounds of Formula I for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, organisms, or associated pathological conditions.

##STR00001##

Formula I compounds include stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof. The dashed lines indicate an optional double bond, and at least one dashed line is a double bond. The substituents are as described.

Methods for treating chronic obstructive pulmonary disease

Methods for treating chronic obstructive pulmonary disease (COPD) in a patient are disclosed. In the methods, a patient having COPD is selected for treatment based on the patient's peak inspiratory flow rate (PIFR) and percent predicted force expiratory volume in one second (FEV.sub.1); and a bronchodilator is administered to the selected patient using a nebulizer. Administration of a bronchodilator to patients having low PIFR and a percent predicted FEV.sub.1 less than 50 percent using a nebulizer as the inhalation delivery device provides significantly greater improvements in trough FEV.sub.1 and trough forced vital capacity (FVC) compared to administration of a bronchodilator to such patients using a dry powder inhaler.

PYRIDAZINONE DERIVATIVE

Provided are: a pyridazinone derivative and/or a pharmaceutically acceptable salt thereof, which is useful as a therapeutic agent and/or a prophylactic agent for diseases in which Nav1.1 is involved and various central nervous system diseases; and a medicine containing the pyridazinone derivative and/or the pharmaceutically acceptable salt thereof as an active ingredient. A compound represented by formula (1) or a pharmaceutically acceptable salt thereof.

##STR00001##

[In the formula, M.sup.1 represents a saturated or partially unsaturated C.sub.4-12 carbocyclic group or the like; R.sup.1 and R.sup.2 independently represent a hydrogen atom or the like; M.sup.2 represents a group represented by formula (2a) or the like; X.sup.1a, X.sup.1b and X.sup.1c independently represent N or the like; X.sup.2, X.sup.3 and X.sup.4 independently represent CR.sup.3 or the like; A.sup.1 and A.sup.2 independently represent N or the like; and R.sup.3 represents a hydrogen atom or the like.]

PYRIDAZINONE DERIVATIVE

Provided are: a pyridazinone derivative and/or a pharmaceutically acceptable salt thereof, which is useful as a therapeutic agent and/or a prophylactic agent for diseases in which Nav1.1 is involved and various central nervous system diseases; and a medicine containing the pyridazinone derivative and/or the pharmaceutically acceptable salt thereof as an active ingredient. A compound represented by formula (1) or a pharmaceutically acceptable salt thereof.

##STR00001##

[In the formula, M.sup.1 represents a saturated or partially unsaturated C.sub.4-12 carbocyclic group or the like; R.sup.1 and R.sup.2 independently represent a hydrogen atom or the like; M.sup.2 represents a group represented by formula (2a) or the like; X.sup.1a, X.sup.1b and X.sup.1c independently represent N or the like; X.sup.2, X.sup.3 and X.sup.4 independently represent CR.sup.3 or the like; A.sup.1 and A.sup.2 independently represent N or the like; and R.sup.3 represents a hydrogen atom or the like.]

COMPOUNDS AND METHODS FOR KRAS MODULATION AND INDICATIONS THEREFOR

Disclosed are compounds of Formula I:

##STR00001## or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer, or a deuterated analog thereof, wherein: R.sup.1, R.sup.2, R.sup.3, X, and Z are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.

COMPOUNDS AND METHODS FOR KRAS MODULATION AND INDICATIONS THEREFOR

Disclosed are compounds of Formula I:

##STR00001## or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer, or a deuterated analog thereof, wherein: R.sup.1, R.sup.2, R.sup.3, X, and Z are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.

SELECTIVE INHIBITORS OF ROCK1 AND ROCK2 PROTEIN KINASES AND USES THEREOF

The present invention relates to novel substituted bicyclic derivatives that can inhibit Rho-kinases and/or Rho-kinase mediated phosphorylation of myosin light chain phosphates, compositions comprising the derivatives, methods for preparing the derivatives, and methods for using the derivatives and/or compositions.

SELECTIVE INHIBITORS OF ROCK1 AND ROCK2 PROTEIN KINASES AND USES THEREOF

The present invention relates to novel substituted bicyclic derivatives that can inhibit Rho-kinases and/or Rho-kinase mediated phosphorylation of myosin light chain phosphates, compositions comprising the derivatives, methods for preparing the derivatives, and methods for using the derivatives and/or compositions.