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

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

Small molecule calpain modulator compositions and pharmaceutical compositions can be prepared and used as therapeutic agents. Exemplary compositions include non-macrocyclic a-keto amide derivatives. The therarapeutic agents can be used for treating fibrotic disease or a resulting secondary disease state or condition. The small molecules can competitively bind with calpastatin and/or inhibit calpain through contact with CAPN1, CAPN2, and/or CAPN9 enzymes.

Small molecule calpain modulator compositions and pharmaceutical compositions can be prepared and used as therapeutic agents. Exemplary compositions include non-macrocyclic a-keto amide derivatives. The therarapeutic agents can be used for treating fibrotic disease or a resulting secondary disease state or condition. The small molecules can competitively bind with calpastatin and/or inhibit calpain through contact with CAPN1, CAPN2, and/or CAPN9 enzymes.

Disclosed herein are novel methods of treating pain in a patient in need thereof by providing to the patient a selective dopamine D3 receptor antagonist/partial agonist which when used with an opioid analgesic, can mitigate the development of opioid dependence, by preventing the need for dose escalation while either maintaining the opioid analgesic effect or providing analgesia with a lower dose of the opioid. In addition, the D3 antagonists/partial agonists described herein may be used to augment the effectiveness of current Medication Assisted Treatment regimens (e.g. methadone or buprenorphine) for the treatment of opioid use disorders.

Pharmaceutical compositions of the invention comprise functionalized benzamide derivatives useful as cyclic GMP-AMP synthase-Stimulator of interferon gene (cGAS-STING) pathway agonists, and useful for treating viral diseases and boost antitumor immunity.

Pharmaceutical compositions of the invention comprise functionalized benzamide derivatives useful as cyclic GMP-AMP synthase-Stimulator of interferon gene (cGAS-STING) pathway agonists, and useful for treating viral diseases and boost antitumor immunity.

Ketamine derivatives and pharmaceutical compositions thereof are disclosed. When administered orally the ketamine derivatives provide increased bioavailability of ketamine in the systemic circulation. The ketamine derivatives can be used to treat neurological diseases, psychological diseases and pain.

Ketamine derivatives and pharmaceutical compositions thereof are disclosed. When administered orally the ketamine derivatives provide increased bioavailability of ketamine in the systemic circulation. The ketamine derivatives can be used to treat neurological diseases, psychological diseases and pain.

A compound of Formula (I): ##STR00001##
or a pharmaceutically acceptable salt thereof, in which Ring X is a 3 to 7 membered monocyclic ring, at least one of R.sub.1, R.sub.2, R.sub.3, and R.sub.4 is OR.sub.5 or CH.sub.2OR.sub.5 and the other R.sub.1, R.sub.2, R.sub.3, and R.sub.4 each independently are halogen, OH, OR.sub.5, CH.sub.2OR.sub.5, CO.sub.2H, OC═OR.sub.6, (C═O)R.sub.6, R.sub.6, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, H, or absent. Also provided herein are therapeutic uses of the compound of Formula (I).