Abstract: The present disclosure provides methods of synthesizing a compound of Formula (P)-I. The method proceeds through several different pathways including several novel chiral separations, a Sonogashira coupling, a zinc mediated reductive cyanation, as well as through various halide containing intermediates. Also disclosed is the multi-kilogram preparation of several novel intermediates.

Abstract: The present disclosure relates to oral compositions of Compound I or a derivative thereof. Methods of use for treating an inflammatory condition are also disclosed.

Abstract: The present disclosure provides methods of synthesizing a compound of Formula (P)-I. The method proceeds through several different pathways including several novel chiral separations, a Sonogashira coupling, a zinc mediated reductive cyanation, as well as through various halide containing intermediates. Also disclosed is the multi-kilogram preparation of several novel intermediates.

Abstract: The present disclosure provides methods of synthesizing a compound of Formula (P)-I and a compound of Formula (P)-II. The method proceeds through several different key pathways including a novel chiral separation as well as through various halide containing intermediates. Also disclosed are single enantiomers of the compound of Formula (P)-II.

Abstract: The present disclosure provides a crystalline form of the methyl/fluoro-pyridinyl-methoxy substituted pyridinone-pyridinyl compound of the structure: XRPD, TGA, and DSC data on the crystalline form, as well as methods preparing the crystalline form, including a multi-kilo scale preparation. Also provided are pharmaceutical compositions and methods of treating p38 mediated diseases, such as lymphoma and auto-inflammatory disease, including rheumatoid arthritis. and methods of maximizing the yield thereof comprising administering of the compound. Also provided is a method of maximizing the yield of said compound via a recycling procedure.

Abstract: The present disclosure provides methods of synthesizing a compound of Formula (P)-I. The method proceeds through several different pathways including several novel chiral separations, a Sonogashira coupling, a zinc mediated reductive cyanation, as well as through various halide containing intermediates. Also disclosed is the multi-kilogram preparation of several novel intermediates.

Abstract: The present invention relates to a needle (1), wherein the needle (1) comprises a channel (12) extending through the needle (1), wherein the needle (1) comprises a needle tip (11), wherein the channel (12) comprises an opening at the needle tip (11), wherein the needle (1) defines an axial direction (x), wherein the axial direction (x) defines a distal direction and a proximal direction, wherein the needle tip (11) is a distal portion of the needle (1), and wherein the needle tip (11) comprises a first surface section (112) and a second surface section (111), wherein the first surface section (112) is arranged at a first angle (?) with respect to the axial direction (x) and the second surface section (111) is arranged at a second angle (?) with respect to the axial direction (x), wherein the first angle is different from the second angle. The present invention also relates to a corresponding apparatus, system and use.

Abstract: A system for use with a block heater connected to an engine for pre-start heating of the engine. The system includes a power source, a relay assembly coupled to the power source, a temperature sensor, and a controller. The relay assembly, when closed, electrically connects the power source to the block heater, to thereby energize the block heater to heat the engine. The temperature sensor senses an ambient temperature indicative of a temperature of the engine. The controller is programmed to selectively activate the relay assembly to energize the block heater such that the engine coupled to the block heater is heated from the sensed ambient temperature to a target temperature at approximately a target time.

Abstract: The present disclosure provides methods of synthesizing a compound of Formula (P)-I. The method proceeds through several different pathways including several novel chiral separations, a Sonogashira coupling, a zinc mediated reductive cyanation, as well as through various halide containing intermediates. Also disclosed is the multi-kilogram preparation of several novel intermediates.

Abstract: The present disclosure relates to oral compositions of Compound I or a derivative thereof. Methods of use for treating an inflammatory condition are also disclosed.

Abstract: Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract: Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract: Disclosed herein are arylpyridinone compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein R1, R2, and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.

Abstract: A system for use with a block heater connected to an engine for pre-start heating of the engine. The system includes a power source, a relay assembly coupled to the power source, a temperature sensor, and a controller. The relay assembly, when closed, electrically connects the power source to the block heater, to thereby energize the block heater to heat the engine. The temperature sensor senses an ambient temperature indicative of a temperature of the engine. The controller is programmed to selectively activate the relay assembly to energize the block heater such that the engine coupled to the block heater is heated from the sensed ambient temperature to a target temperature at approximately a target time.

Abstract: Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases cases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract: Disclosed herein are arylpyridinone compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein R1, R2, and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.

Abstract: Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseeases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract: Disclosed herein are heterocyclic compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein R1, R2, and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.

Abstract: Disclosed herein are heterocyclic compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein R1, R2, and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.

Abstract: Disclosed herein are arylpyridinone compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein R1, R2, and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.