Augmented or synergized anti-inflammatory constructs are disclosed including anti-inflammatory terpenes and/or vanilloids covalently conjugated to one another so that the activity of the conjugate is greater than the sum of its parts. Also disclosed are methods of improving the potency of an anti-inflammatory terpene or vanilloid by linking it to another anti-inflammatory terpene or vanilloid via a carbamate linkage, where the potency of the conjugate is greater than the sum of its parts.

The disclosure provides recording materials include fluorene derivatized monomers and polymers for use in volume Bragg gratings, including, but not limited to, volume Bragg gratings for holography applications. Several fluorene structures are disclosed: simply substituted fluorenes, cardo-fluorenes, and spiro-fluorenes. Fluorene derivatized polymers in Bragg gratings applications lead to materials with higher refractive index, low birefringence, and high transparency. Fluorene derivatized monomers/polymers can be used in any volume Bragg gratings materials, including two-stage polymer materials where a matrix is cured in a first step, and then the volume Bragg grating is written by way of a second curing step of a monomer.

The present invention relates to the synthesis of N-trifluoromethylcarbonyl compounds starting from isothiocyanates, which can be converted into N-trifluoromethylcarbamoyl fluorides or similar compounds, which later on can be derivatized further to amides, ureas, carbamates, thiocarbamates and selenocarbamates.

This disclosure relates to modulators of liver receptor homologue 1 (LRH-1) and methods of managing disease and conditions related thereto. In certain embodiments, modulators are derivatives of hexahydropentalene. In certain embodiments, this disclosure relates to methods of treating or preventing cancer, diabetes, or cardiovascular disease by administering an effective amount of a hexahydropentalene derivative disclosed herein.

This disclosure relates to modulators of liver receptor homologue 1 (LRH-1) and methods of managing disease and conditions related thereto. In certain embodiments, modulators are derivatives of hexahydropentalene. In certain embodiments, this disclosure relates to methods of treating or preventing cancer, diabetes, or cardiovascular disease by administering an effective amount of a hexahydropentalene derivative disclosed herein.

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases, disorders and conditions.

The present invention is directed to methods for the asymmetric synthesis of esketamine. The present invention is further directed to key intermediates in the asymmetric esketamine synthesis. In one embodiment, the invention is an asymmetric synthesis of esketamine comprising the conversion of (S)-2′-chloro-2-methoxy-3,4,5,6-5 tetrahydro-[1,1′-biphenyl]-3-yl carbamate to (S)-2′-chloro-1-isocyanato-6-methoxy-1,2,3,4-tetrahydro-1,1′-biphenyl.

##STR00001##

The present invention is directed to methods for the asymmetric synthesis of esketamine. The present invention is further directed to key intermediates in the asymmetric esketamine synthesis. In one embodiment, the invention is an asymmetric synthesis of esketamine comprising the conversion of (S)-2′-chloro-2-methoxy-3,4,5,6-5 tetrahydro-[1,1′-biphenyl]-3-yl carbamate to (S)-2′-chloro-1-isocyanato-6-methoxy-1,2,3,4-tetrahydro-1,1′-biphenyl.

##STR00001##

The present invention is directed to methods for the asymmetric synthesis of esketamine. The present invention is further directed to key intermediates in the asymmetric esketamine synthesis. In one embodiment, the invention is an asymmetric synthesis of esketamine comprising the conversion of (S)-2′-chloro-2-methoxy-3,4,5,6-5 tetrahydro-[1,1′-biphenyl]-3-yl carbamate to (S)-2′-chloro-1-isocyanato-6-methoxy-1,2,3,4-tetrahydro-1,1′-biphenyl.

##STR00001##

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.