Abstract: Provided are compounds of the Formula I, and salts, hydrates and solvates thereof: wherein R1, R2, R3 and Q1 are each as defined in the specification. The compounds are inhibitors of EGFR, including mutated forms of EGFR (for example EGFR comprising a T790M mutation, a deletion in exon 19 (e.g. A740-A750), an exon 20 insertion, a mutation at L858R and/or a C797S mutation) that confer resistance to existing EGFR inhibitors.

Abstract: Compounds of Formula (I) or their pharmaceutically acceptable salts can inhibit the G12C, G12D, G12V, and/or G13D mutants of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

Abstract: The invention provides a compound of formula (0): or a pharmaceutically acceptable salt, N-oxide or tautomer thereof; wherein: n is 1 or 2; X is CH or N; Y is selected from CH and C—F; Z is selected from C—Rz and N; R1 is selected from: -(Alk1)t-Cyc1; wherein t is 0 or 1; Optionally substituted C1-6 acyclic hydrocarbon groups R2 is selected from hydrogen; halogen; and C1-8 hydrocarbon groups optionally substituted with one or more fluorine atoms; R3 is hydrogen or a group L1-R7; R4 is selected from hydrogen; methoxy; and optionally substituted C1-3 alkyl; and R4a is selected from hydrogen and a C1-3 alkyl group; wherein Rz, Alk1, Cyc1, L1 and R7 are defined herein; provided that the compound is other than 6-benzyl-3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and 3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and salts and tautomers thereof.

Abstract: The disclosed compounds relate to treatments and therapies for protein kinase-associated disorders. There is also a need for compounds useful in the treatment or prevention or amelioration of one or more symptoms of cancer, transplant rejections, and autoimmune diseases. Furthermore, there is a need for methods for modulating the activity of protein kinases, such as CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8 and CDK9, using the compounds provided herein.

Abstract: Provided are compounds of the Formula I, and salts, hydrates and solvates thereof: wherein R1, V1, RN and Q1 are each as defined in the specification. The compounds are inhibitors of EGFR, including mutated forms of EGFR (for example EGFR comprising a T790M mutation, a deletion in exon 19 (e.g. A740-A750), an exon 20 insertion, a mutation at L858R and/or a C797S mutation) that confer resistance to existing EGFR inhibitors.

Abstract: The invention provides new pyrazine derivatives of formula (I): or a tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the substituents are as defined herein. The invention also provides pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

Abstract: A catheter device may include a body. The body can include a handle body, an actuator, a force sensor, and a displacement sensor. The catheter device may include a scaffold. The scaffold can include a plurality of splines. Each of the plurality of splines can extend transversely and longitudinally along the body. The deployable scaffold can move between a first position to a second position and all positions in-between. The catheter device may further include a shaft assembly. The shaft assembly can include an outer shaft and inner shaft coupled to the body portion. In the first position, the scaffold can be in a collapsed state. In the second position, the scaffold can be in an expanded state. The force sensor and displacement sensor may be located in the body to measure force and/or displacement translated by the inner and outer shaft from the scaffold.

Abstract: The invention provides new pyrazine derivatives of formula (I): or a tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the substituents are as defined herein. The invention also provides pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

Abstract: A soft tissue retraction system may include a support body. A soft tissue retraction system may include a bone engaging concavity on a first side of the support body. A soft tissue retraction system may include a soft tissue retracting surface on a second side of the support body. The system may include a first guide configured to receive a first pin to anchor the first pin into a bone when the bone is positioned within the bone engaging concavity. The system may include a second guide configured to receive a second pin to anchor the second pin into the bone when the bone is positioned within the bone engaging concavity.

Abstract: The invention relates to new bicyclic heterocycle compounds, to pharmaceutical compositions comprising the compounds and to the use of the compounds in the treatment of diseases, e.g. cancer.

Abstract: The invention provides a compound of formula (1). or tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the various substituents are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds.

Abstract: The invention relates to processes for preparing isoindolin-1-one derivatives, and in particular processes for preparing (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid. The invention also relates to crystalline forms of the compound (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid and its salts.

Abstract: The invention relates to new bicyclic heterocycle compounds, to pharmaceutical compositions comprising the compounds and to the use of the compounds in the treatment of diseases, e.g. cancer.

Abstract: The invention provides a compound of formula (0): or a pharmaceutically acceptable salt, N-oxide or tautomer thereof; wherein: n is 1 or 2; X is CH or N; Y is selected from CH and C—F; Z is selected from C—Rz and N; R1 is selected from: -(Alk1)t-Cyc1; wherein t is 0 or 1; Optionally substituted C1-6 acyclic hydrocarbon groups R2 is selected from hydrogen; halogen; and C1-8 hydrocarbon groups optionally substituted with one or more fluorine atoms; R3 is hydrogen or a group L1-R7; R4 is selected from hydrogen; methoxy; and optionally substituted C1-3 alkyl; and R4a is selected from hydrogen and a C1-3 alkyl group; wherein Rz, Alk1, Cyc1, L1 and R7 are defined herein; provided that the compound is other than 6-benzyl-3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and 3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and salts and tautomers thereof.

Abstract: An orthodontic device can include a bracket configured to support an orthodontic wire. The orthodontic device can include a locking assembly coupled to the bracket and switchable between a plurality of operational modes. The plurality of operational modes can comprise a first sliding mode in which the orthodontic wire is slidable relative to the bracket and a second locked mode in which the orthodontic wire is slidably locked relative to the bracket.

Abstract: A depth sensing dilator system for dilating a penetration in a tissue plane includes an elongate flexible body, having a proximal end and a distal end. The body has a tapered dilator segment, and at least a first electrode on a distal end of the body. The system includes a processor and a user interface output device. The processor is configured to send a first signal to the output device when a change in impedance at the first electrode indicates that the first electrode has reached a predetermined relationship with the tissue plane.

Abstract: The invention relates to processes for preparing isoindolin-1-one derivatives, and in particular processes for preparing (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid. The invention also relates to crystalline forms of the compound (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid and its salts.

Abstract: The invention provides a compound of formula (I): or tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the various substituents are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds.

Abstract: Compounds of Formula (I) or (Ia) or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or (Ia) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.