Disclosed is a method for efficiently synthesizing primary amines, which comprises using carbonyl compounds or alcohol compounds as reaction substrate, liquid ammonia or alcohol solutions of ammonia as nitrogen source, and hydrogen as hydrogen source, and reacting in reaction medium catalyzed by a cobalt-based catalyst to obtain the primary amines. Due to high catalytic activity, the method can realize the reductive amination of carbonyl compounds and the hydrogen-borrowing amination of alcohol compounds at low temperatures in a short time to obtain the primary amines with high yield, and is applicable to a wide range of substrates. The obtained primary amines can be used as raw materials with high extra value for producing polymers, medicines, dyes and surfactants. Further, the cobalt-based catalyst has a good industrial application prospect because it is magnetic which can facilitate separation and recycling of the catalyst. Moreover, the inexpensive cobalt-based catalyst can significantly reduce industrialization cost.

The present invention describes a method of preventing, ameliorating and/or treating disorders or diseases associated with the integrated stress response (ISR) involving the p-eIF2α pathway arising from various cellular stresses such as oxidative stress, hypoxia and ER stress, chronic or prolonged bio-mechanical stress. In one embodiment, the present invention provides a method which prevents or alleviates aberrant cell differentiation that is caused by the activation of the integrated stress response and thereby prevents or alleviates conditions, disorders or diseases resulting therefrom. In one embodiment, ISR-associated diseases subject to the present invention include but are not limited to skeletal disorders including disc degeneration, MCDS and other skeletal dysplasias, cancers, inflammatory diseases, diabetes, fibrosis, obesity and neurodegenerative diseases. In another embodiment, the present invention provides a method of using a p-eIF2α-modulator for the prevention or treatment of conditions, disorders or diseases described herein.

The present invention describes a method of preventing, ameliorating and/or treating disorders or diseases associated with the integrated stress response (ISR) involving the p-eIF2α pathway arising from various cellular stresses such as oxidative stress, hypoxia and ER stress, chronic or prolonged bio-mechanical stress. In one embodiment, the present invention provides a method which prevents or alleviates aberrant cell differentiation that is caused by the activation of the integrated stress response and thereby prevents or alleviates conditions, disorders or diseases resulting therefrom. In one embodiment, ISR-associated diseases subject to the present invention include but are not limited to skeletal disorders including disc degeneration, MCDS and other skeletal dysplasias, cancers, inflammatory diseases, diabetes, fibrosis, obesity and neurodegenerative diseases. In another embodiment, the present invention provides a method of using a p-eIF2α-modulator for the prevention or treatment of conditions, disorders or diseases described herein.

Provided are methods related to treating congenital adrenal hyperplasia in a subject in need thereof comprising administering 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-prop-2-ynyl-1,3-thiazol-2-amine (Formula 1), or a pharmaceutically acceptable salt thereof. Further provided are pharmaceutical formulations and solid forms of 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-prop-2-ynyl-1,3-thiazol-2-amine, or a pharmaceutically acceptable salt thereof, and their use in the treatment of congenital adrenal hyperplasia (CAH).

Provided are methods related to treating congenital adrenal hyperplasia in a subject in need thereof comprising administering 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-prop-2-ynyl-1,3-thiazol-2-amine (Formula 1), or a pharmaceutically acceptable salt thereof. Further provided are pharmaceutical formulations and solid forms of 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-prop-2-ynyl-1,3-thiazol-2-amine, or a pharmaceutically acceptable salt thereof, and their use in the treatment of congenital adrenal hyperplasia (CAH).

An improved method for synthesizing a compound according to formula (I) by reaction of a compound of formula (II) with a sulfinamide according to formula (III). The resultant compound is then reduced and hydrolyzed, and optionally alkylated or arylated to arrive at the compound according to formula (I).

##STR00001##

An improved method for synthesizing a compound according to formula (I) by reaction of a compound of formula (II) with a sulfinamide according to formula (III). The resultant compound is then reduced and hydrolyzed, and optionally alkylated or arylated to arrive at the compound according to formula (I).

##STR00001##

Provided herein, inter alia, are compounds and methods useful for modulating the translational effects of eIF2α phosphorylation, the Integrated Stress Response (ISR), and the unfolded protein response (UPR); for treating diseases; for increasing protein production, and for improving long-term memory.

Provided herein, inter alia, are compounds and methods useful for modulating the translational effects of eIF2α phosphorylation, the Integrated Stress Response (ISR), and the unfolded protein response (UPR); for treating diseases; for increasing protein production, and for improving long-term memory.

The present invention provides small molecule drugs and pharmaceutical compositions for the treatment and prevention of diseases related to the formation of Aβ42 oligomers in a subject. It further provides a method of reducing formation of or disrupting Aβ42 oligomers in a subject, the method comprising the step of administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition.