Compounds of formula (I) wherein: X is —O—, —S(O).sub.r—, —CH.sub.2—, or —NR—, wherein r is 0, 1, or 2; X.sup.1, X.sup.2, and X.sup.5 are each independently CR.sup.7 or N; one of X.sup.3 or X.sup.4 is C and is attached by a single bond to -L-, and the other is CR.sup.7 or N, provided that no more than three of X.sup.1, X.sup.2, X.sup.3, X or X.sup.5 are N; Ring A is monocyclic C.sub.5-6scycloalkyl or a 5- to 6-membered monocyclic heterocyclyl comprising from 1 to 5 heteroatoms independently selected from N, S, or O; wherein Ring A is further optionally substituted with from 1 to 3 R.sup.4; provided that Ring A is not morpholinyl, thiomorpholinyl or tetrahydro-2H-pyranyl; L is a bond, —O—, —NR—, —S(O).sub.n—, —CH.sub.2—, or —C(O)—, wherein n is 0, 1, or 2; 1 2 L.sup.1 is an C.sub.1-8alkylene, C.sub.3-scycloalkylene, —CH.sub.2-L.sup.2-, or a 3- to 8-membered heterocyclylene comprising 1 to 5; R.sup.1 is C.sub.6-20alkyl or a monocyclic C.sub.3-8cycloalkyl; wherein said C.sub.3-8cycloalkyl is substituted with at least one R.sup.6 and may be optionally substituted with from 1 to 5 additional R.sup.6 substituents, wherein R.sup.6 for each occurrence is independently selected; and R.sup.2 is —C(O)OR.sup.3, —C(O)N(R.sup.3)—S(O).sub.2R.sup.3, —S(O).sub.2OR.sup.3, —C(O)NHC(O)R.sup.3, —Si(O)OH, —B(OH).sub.2, —N(R.sup.3)S(O).sub.2R.sup.3, —S(O).sub.2N(R.sup.3).sub.2, —O—P(O)(OR.sup.3).sub.2, or —P(O)(OR.sup.3).sub.2, —CN, —S(O).sub.2NHC(O)R.sup.3, —C(O)NHS(O).sub.2R3, —C(O)NHOH, —C(O)NHCN, —CH(CF.sub.3)OH, —C(CF.sub.3).sub.2OH, or a selected heteroaryl or heterocyclyl; and pharmaceutically acceptable salts thereof, can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX). ##STR00001##

The present disclosure provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

The present disclosure provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

The subject matter disclosed herein is directed to novel She inhibitors of Formula (II). These compounds are useful for treating impaired insulin sensitivity, glucose tolerance, obesity, diabetes, metabolic syndrome, NAFLD, NASH, PSC, PBC, or other metabolic syndrome component conditions. ##STR00001##

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 provides a cationic lipid, which allow nucleic acids to be easily introduced into cells, represented by formula (I) (wherein: R.sup.1 and R.sup.2 are, the same or different, alkenyl, etc, and X.sup.1 and X.sup.3 are hydrogen atoms, or are combined together to form a single bond or alkylene, and X.sup.3 is absent or is alkyl, etc, Y is absent or anion, a and b are, the same or different, 0 to 3, and L.sup.3 is a single bond, etc, R.sup.3 is alkyl, etc, L.sup.1 and L.sup.2 are —O—, —CO—O— or —O—CO—), a composition comprising the cationic lipid and a nucleic acid, and a method for introducing a nucleic acid into a cell by using the composition comprising the cationic lipid and the nucleic acid, and the like. ##STR00001##

The present invention provides a cationic lipid, which allow nucleic acids to be easily introduced into cells, represented by formula (I) (wherein: R.sup.1 and R.sup.2 are, the same or different, alkenyl, etc, and X.sup.1 and X.sup.3 are hydrogen atoms, or are combined together to form a single bond or alkylene, and X.sup.3 is absent or is alkyl, etc, Y is absent or anion, a and b are, the same or different, 0 to 3, and L.sup.3 is a single bond, etc, R.sup.3 is alkyl, etc, L.sup.1 and L.sup.2 are —O—, —CO—O— or —O—CO—), a composition comprising the cationic lipid and a nucleic acid, and a method for introducing a nucleic acid into a cell by using the composition comprising the cationic lipid and the nucleic acid, and the like. ##STR00001##

Novel direct thrombin inhibitors are provided herein, along with methods for their use as anticoagulants. The direct thrombin inhibitors described herein are useful in treating and/or preventing thromboembolism and bleeding or clotting disorders. Also provided herein are methods for inhibiting thrombin in a cell using the compounds and compositions described herein.

Novel direct thrombin inhibitors are provided herein, along with methods for their use as anticoagulants. The direct thrombin inhibitors described herein are useful in treating and/or preventing thromboembolism and bleeding or clotting disorders. Also provided herein are methods for inhibiting thrombin in a cell using the compounds and compositions described herein.

The present disclosure provides compounds and methods for inhibiting or degrading the N-terminal domain of the androgen receptor, as well as methods for treating cancers such as prostate cancer.