Provided is a process for the preparation of certain 1,4-bicyclo[2.2.2]octane derivatives. The new synthetic procedure involves treating 1,4-dimethylene cyclohexane with an oxidizing agent in the presence of a transition metal catalyst to afford an oxo-substituted bicyclo[2.2.2]octane species. This intermediate structure can then be further derivatized. The processes of this disclosure thus affords a novel and simplified means for the commercial production of a wide variety of bicyclo[2.2.2]octane derivatives.

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

Disclosed herein are secondary amine compounds that inhibit tRNA synthetase. The compounds of the invention are useful in inhibiting tRNA synthetase in Gram-negative bacteria and are useful in killing Gram-negative bacteria. The secondary amine compounds of the invention are also useful in the treatment of tuberculosis.

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof:
X-A-Y-L-R  (I)
which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

The application relates to a compound of Formula (I′) or (I): ##STR00001##
or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which modulates the activity of SSAO, a pharmaceutical composition comprising a compound of Formula (I′) or (I), and a method of treating or preventing a disease in which SSAO plays a role.

The present application discloses a compound of formula (I) or a salt thereof: (I) and compositions comprising such compound or salt thereof. The use of such compound, salt thereof or composition comprising same for treating anemia or leukopenia, fibrosis, cancer, hypertension and/or a metabolic condition in a subject is also disclosed.

A TRPM8 antagonist is provided that comprises the following the formula (I) described herein. In the formula (I), R.sub.1 is selected from a cycloalkyl, a bicycloalkyl, or a tricycloalkyl group. Each R.sub.1 group has 5 to 12 carbon atoms. Further, each R.sub.1 group is optionally substituted with an alkyl group having 1 to 5 carbons atoms or with a cycloalkyl group having 4 to 12 carbon atoms, and each R.sub.1 group is optionally saturated or partially unsaturated. Methods for treating pain are further provided and comprise administering to a subject in need thereof an effective amount of a TRPM8 antagonist comprising the formula (I).

Disclosed herein are secondary amine compounds that inhibit tRNA synthetase. The compounds of the invention are useful in inhibiting tRNA synthetase in Gram-negative bacteria and are useful in killing Gram-negative bacteria. The secondary amine compounds of the invention are also useful in the treatment of tuberculosis.

Provided is a compound of Formula (I):

##STR00001## wherein the variable groups are defined herein.

A method for preparing (2S,3S)-3-amino-bicyclo[2.2.2]octane-2-carboxylate is in the field of pharmaceutical intermediate synthesis. The method uses 3-carbonyl-bicyclo[2.2.2]octane-2-carboxylate as the starting material and performs reductive amination, alkalinity configuration flip, and hydrogenation to remove the protecting group in sequence to obtain the target product. This synthesis method of (2S,3S)-3-amino-bicyclo[2.2.2]octane-2-carboxylate is characterized by a novel route, mild reaction conditions and low cost, with a yield of more than 65%.