There is disclosed pyridine-and pyrimidinecarboxamide compounds useful as pharmaceutical agents, synthesis processes, and pharmaceutical compositions which include pyridine-and pyrimidinecarboxamides compounds. More specifically, there is disclosed a genus of CXCR2 inhibitor compounds that are useful for treating a variety of inflammatory and neoplastic disorders.

The present application discloses compounds capable of modulating the activity of histone demethylases (HDMEs), which are useful for prevention and/or treatment of diseases in which genomic dysregulation is involved in the pathogenesis, such as e.g. cancer. The present application also discloses pharmaceutical compositions comprising said compounds and the use of such compounds as a medicament. The compounds take the form ##STR00001##

The present invention relates to compounds useful as inhibitors of PI3K, particularly of PI3K. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

The present invention relates to spiro-cyclic amine derivatives of the formula (I) ##STR00001## wherein R1 is selected from cyano, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkyl each optionally substituted with CN or one or more fluoro atoms, (3-6C)cycloalkyl, (4-6C)cycloalkenyl or a (8-10C)bicyclic group, each optionally substituted with halogen or (1-4C)alkyl, phenyl, biphenyl, naphthyl, each optionally substituted with one or more substituents independently selected from halogen, cyano, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (1-6C)alkoxy optionally substituted with one or more fluoro atoms, amino, di(1-4C)alkylamino and (3-6C)cycloalkyl optionally substituted with phenyl which may be substituted with (1-4C)alkyl or halogen, phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each optionally substituted with (1-4C)alkyl optionally substituted with one or more fluoro atoms, monocyclic heterocycle optionally independently substituted with halogen, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (3-6C)cycloalkyl, or phenyl optionally substituted with (1-4C)alkyl or halogen, and bicyclic heterocycle optionally substituted with halogen or (1-4C)alkyl optionally substituted with one or more fluoro atoms; Y(C.sub.n-alkylene)-X is a linking group wherein Y is attached to R1 and selected from a bond, O, CO, S, SO, SO.sub.2, NH, CHCH, C(CF.sub.3)CH, CC, CH.sub.2O, OCO, COO, CONH, NHCO, and trans-cyclopropylene; n is an integer from 0 to 10; and X is attached to the phenylene/pyridyl moiety and selected from a bond, O, S, SO, SO.sub.2, NH, CO, CHCH, and trans-cyclopropylene; R2 is H or independently selected from one or more substituents selected from halogen, (1-4C)alkoxy and (1-4C)alkyl optionally substituted with one or more fluor atoms; and R3 is (1-4C)alkylene-R4 wherein the alkylene group may be substituted with one or more halogen atoms or with (CH.sub.2).sub.2 to form a cyclopropyl moiety, or R3 is (3-6C)cycloalkylene-R4, CH.sub.2-(3-6C)cycloalkylene-R4, (3-6C)cycloalkylene-CH.sub.2R4 or COCH.sub.2R4, wherein R4 is OH, PO.sub.3H.sub.2, OPO.sub.3H.sub.2, COOH, COO(1-4C)alkyl or tetrazol-5-yl; Q is a bond or O; W-T- is selected from CHCH, CH.sub.2CH.sub.2, CH.sub.2O, OCH.sub.2, OCH.sub.2CH.sub.2, and COO; R5 is H or independently selected from one or more halogens; Z is CH, CR2 or N; and A represents a morpholine ring structure or a 5-, 6- or 7-membered cyclic amine; or a pharmaceutically acceptable salt, a solvate or hydrate thereof or one or more N-oxides thereof. The compounds of the invention have affinity to S1P receptors and may be used in the treatment, alleviation o

The present invention relates to spiro-cyclic amine derivatives of the formula (I) ##STR00001## wherein R1 is selected from cyano, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkyl each optionally substituted with CN or one or more fluoro atoms, (3-6C)cycloalkyl, (4-6C)cycloalkenyl or a (8-10C)bicyclic group, each optionally substituted with halogen or (1-4C)alkyl, phenyl, biphenyl, naphthyl, each optionally substituted with one or more substituents independently selected from halogen, cyano, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (1-6C)alkoxy optionally substituted with one or more fluoro atoms, amino, di(1-4C)alkylamino and (3-6C)cycloalkyl optionally substituted with phenyl which may be substituted with (1-4C)alkyl or halogen, phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each optionally substituted with (1-4C)alkyl optionally substituted with one or more fluoro atoms, monocyclic heterocycle optionally independently substituted with halogen, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (3-6C)cycloalkyl, or phenyl optionally substituted with (1-4C)alkyl or halogen, and bicyclic heterocycle optionally substituted with halogen or (1-4C)alkyl optionally substituted with one or more fluoro atoms; Y(C.sub.n-alkylene)-X is a linking group wherein Y is attached to R1 and selected from a bond, O, CO, S, SO, SO.sub.2, NH, CHCH, C(CF.sub.3)CH, CC, CH.sub.2O, OCO, COO, CONH, NHCO, and trans-cyclopropylene; n is an integer from 0 to 10; and X is attached to the phenylene/pyridyl moiety and selected from a bond, O, S, SO, SO.sub.2, NH, CO, CHCH, and trans-cyclopropylene; R2 is H or independently selected from one or more substituents selected from halogen, (1-4C)alkoxy and (1-4C)alkyl optionally substituted with one or more fluor atoms; and R3 is (1-4C)alkylene-R4 wherein the alkylene group may be substituted with one or more halogen atoms or with (CH.sub.2).sub.2 to form a cyclopropyl moiety, or R3 is (3-6C)cycloalkylene-R4, CH.sub.2-(3-6C)cycloalkylene-R4, (3-6C)cycloalkylene-CH.sub.2R4 or COCH.sub.2R4, wherein R4 is OH, PO.sub.3H.sub.2, OPO.sub.3H.sub.2, COOH, COO(1-4C)alkyl or tetrazol-5-yl; Q is a bond or O; W-T- is selected from CHCH, CH.sub.2CH.sub.2, CH.sub.2O, OCH.sub.2, OCH.sub.2CH.sub.2, and COO; R5 is H or independently selected from one or more halogens; Z is CH, CR2 or N; and A represents a morpholine ring structure or a 5-, 6- or 7-membered cyclic amine; or a pharmaceutically acceptable salt, a solvate or hydrate thereof or one or more N-oxides thereof. The compounds of the invention have affinity to S1P receptors and may be used in the treatment, alleviation o

Compounds of Formula I that inhibit the activity of the diacylglycerol acyltransferase 2 (DGAT2) and their uses in the treatment of diseases linked thereto in animals are described herein.

Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient an effective amount of a compound represented by Structural Formula (I): ##STR00001##
or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (IA) are as described herein. A compound is represented by Structural Formula (IA) or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (IA) are as described herein. A pharmaceutical composition comprises an effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.

Provided are substituted benzaldehydes and derivatives thereof that act as allosteric modulators of hemoglobin, methods and intermediates for their preparation, pharmaceutical compositions comprising the modulators, and methods for their use in treating disorders mediate by hemoglobin and disorders that would benefit from increased tissue oxygenation.

Compounds and compositions comprising compounds that inhibit glutaminase are described herein. Also described herein are methods of using the compounds that inhibit glutaminase in the treatment of cancer.

Disclosed are compounds of formula 1: ##STR00001##
which are useful as inhibitors of TBK1. Also disclosed are pharmaceutical compositions which contain the compounds, methods for treatment of conditions associated with TBK1, and processes for making the compounds and intermediates thereof.