The present disclosure provides crystalline carfilzomib form M1 and a process for the preparation thereof. Further disclosed are processes for the preparation of amorphous carfilzomib using crystalline form M1 as a starting material. The present disclosure also relates to an improved process for the preparation of carfilzomib.

The invention provides oxaspiro[2.5]octane derivatives and analogs, methods for preparation thereof, intermediates thereto, pharmaceutical compositions, and uses thereof in the treatment of various disorders and conditions, such as overweight and obesity.

The invention provides oxaspiro[2.5]octane derivatives and analogs, methods for preparation thereof, intermediates thereto, pharmaceutical compositions, and uses thereof in the treatment of various disorders and conditions, such as overweight and obesity.

-Substituted -amino acids, -substituted -amino acid derivatives, and -substituted -amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The -substituted -amino acid derivatives and -substituted -amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the -substituted -amino acid derivatives and -substituted -amino acid analogs and methods of using the compounds for treating cancer are also disclosed. The -substituted -amino acid derivatives and -substituted -amino acid analogs exhibit selective uptake in tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The -substituted -amino acid derivatives and -substituted -amino acid analogs and (bio)isosteres exhibit cytotoxicity toward several tumor types.

-Substituted -amino acids, -substituted -amino acid derivatives, and -substituted -amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The -substituted -amino acid derivatives and -substituted -amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the -substituted -amino acid derivatives and -substituted -amino acid analogs and methods of using the compounds for treating cancer are also disclosed. The -substituted -amino acid derivatives and -substituted -amino acid analogs exhibit selective uptake in tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The -substituted -amino acid derivatives and -substituted -amino acid analogs and (bio)isosteres exhibit cytotoxicity toward several tumor types.

The present invention relates to a process for preparing 3-amino tetrahydropyrans and, more particularly, to an improved method for synthesizing a 2,3,5-substituted tetrahydropyran derivative, intermediate being used in the preparation of dipeptidyl peptidase-IV enzyme inhibitors (DPP-4 inhibitors).

A dry sprinkler includes a flexible tube section that maintains a pressurized fluid, such as a liquid antifreeze solution, between a first end and a second end. A first seal prevents fluid from a supply line from entering the flexible tube section. The first seal is maintained in a sealed position by a pressure of the pressurized fluid. A sprinkler head is coupled to the second end of the flexible tube section, and includes a frame, an output orifice, a deflector, a second seal that seals the output orifice, and a thermally responsive element configured to maintain the second seal in a sealed position when the thermally responsive element is in a non-responsive state. A differential pressure controller maintains a ratio between the pressure of the pressurized fluid in the flexible tube section and a pressure of a supply fluid in the supply line to at least a certain ratio.

The invention relates to an improved process for making monomeric triglycidyl compounds, wherein the triglycidyl compounds include N, O-triglycidyl compounds containing at least one primary aromatic amine and one phenolic functional group attached to the same or a different aromatic ring. The methods of the present invention result in the production of N, O-triglycidyl compounds, such as those of formula I and II. The improved process is energy efficient, environment friendly, and results in increased yields of product. The methods of the present invention can be performed in the absence of protic organic co-solvents during the reaction of an epihalohydrin with an aminophenol, such as compounds of formula II and IV, which provides an intermediate halohydrin compound. The methods of the present invention may also be performed in the absence of a phase transfer catalyst. ##STR00001##

The invention relates to an improved process for making monomeric triglycidyl compounds, wherein the triglycidyl compounds include N, O-triglycidyl compounds containing at least one primary aromatic amine and one phenolic functional group attached to the same or a different aromatic ring. The methods of the present invention result in the production of N, O-triglycidyl compounds, such as those of formula I and II. The improved process is energy efficient, environment friendly, and results in increased yields of product. The methods of the present invention can be performed in the absence of protic organic co-solvents during the reaction of an epihalohydrin with an aminophenol, such as compounds of formula II and IV, which provides an intermediate halohydrin compound. The methods of the present invention may also be performed in the absence of a phase transfer catalyst. ##STR00001##

A dry sprinkler includes a flexible tube section that maintains a pressurized fluid, such as a liquid antifreeze solution, between a first end and a second end. A first seal prevents fluid from a supply line from entering the flexible tube section. The first seal is maintained in a sealed position by a pressure of the pressurized fluid. A sprinkler head is coupled to the second end of the flexible tube section, and includes a frame, an output orifice, a deflector, a second seal that seals the output orifice, and a thermally responsive element configured to maintain the second seal in a sealed position when the thermally responsive element is in a non-responsive state. A differential pressure controller maintains a ratio between the pressure of the pressurized fluid in the flexible tube section and a pressure of a supply fluid in the supply line to at least a certain ratio.