The present invention relates to novel pyrimido-diazepinone compounds, methods of modulating protein kinases, including MPS1 (TTK), ERK5 (BMK1, MAPK7), polo kinase 1, 2, 3, or 4, Ack1, Ack2, Abl, DCAMKL1, ABL1, Abl mutants, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNK1, PLK1, ULK2, PLK4, PRKD1, PRKD2, PRKD3, ROS1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, Axl, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR, PKB, PKC, Raf, ROCK-H, Rsk1, SGK, TrkA, TrkB and TrkC, and the use of such compounds in the treatment of various diseases, disorders or conditions.

The present invention relates to PDEI inhibitory compounds of Formula I as described herein, processes for their production, their use as pharmaceuticals and pharmaceutical compositions comprising them.

Disclosed are a pyridyl imidazobenzodiazepine propionate (compound 1) and the synthesis and use thereof. Also provided are intermediates for the preparation. Compound 1 provided by the present invention has an obvious venous anesthesia activity equivalent to that of the positive control drug remimazolam p-toluenesulfonate or remimazolam besylate. In addition, compound 1 can be significantly reduced in mouse model experiments, and same can even overcome common limb jitters, head tilting, opisthotonus and other side effects caused by the remimazolam besylate or remimazolam p-toluenesulfonate as a drug during development in preclinical animal experiments, thereby allowing same to be used in the preparation of intravenous anesthetics. The structural general formula of compound 1 is as follows, wherein each group and substituent are as defined in the description. ##STR00001##

The present disclosure provides bioorthogonal linkers and reagents, including trans-cyclooctene (TCO)- and tetrazine (Tz)-containing compounds. In a general aspect, the present disclosure provides reagents, conjugates, and bioactive molecules containing a trans-cyclooctene (TCO) fragment. Examples of TCO fragments include: Formulae (I) and (II).

##STR00001##

Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.

Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.

The present invention relates to novel pyrimido-diazepinone compounds, methods of modulating protein kinases, including MPS1 (TTK), ERK5 (BMK1, MAPK7), LRKK2, EphA2, polo kinase 1, 2, 3, or 4, Ack1, Ack2, Abl, DCAMKL1, ABL1, Abl mutants, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNK1, PLK1, ULK2, PLK4, PRKD1, PRKD2, PRKD3, ROS1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, Axl, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR, PKB, PKC, Raf, ROCK-H, Rsk1, SGK, TrkA, TrkB and TrkC, and the use of such compounds in the treatment of various diseases, disorders or conditions.

The present invention relates to novel pyrimido-diazepinone compounds, methods of modulating protein kinases, including MPS1 (TTK), ERK5 (BMK1, MAPK7), LRKK2, EphA2, polo kinase 1, 2, 3, or 4, Ack1, Ack2, Abl, DCAMKL1, ABL1, Abl mutants, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNK1, PLK1, ULK2, PLK4, PRKD1, PRKD2, PRKD3, ROS1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, Axl, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR, PKB, PKC, Raf, ROCK-H, Rsk1, SGK, TrkA, TrkB and TrkC, and the use of such compounds in the treatment of various diseases, disorders or conditions.

Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.

Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.