The invention provides amides that inhibit cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrates and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.

Provided herein are anti-fibrotic compounds, in particular those of Formula (I), that inhibit the TGF-beta signaling pathway. Also provided are pharmaceutical compositions comprising the anti-fibrotic compounds, and methods of treating diseases or conditions associated with fibrosis, inflammation, and benign or malignant neoplastic diseases in a subject by administering a compound or composition described herein.

Disclosed herein are methods and processes of preparing niraparib and pharmaceutically acceptable salts thereof, and intermediates and their salts useful for the synthesis of niraparib.

The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity.

The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity.

The present invention provides a tricyclic compound, its preparation method and medical use. The tricyclic compound is a compound having the structure of the following formula (I), and its pharmaceutically acceptable salt, prodrug, tautomer, stereoisomers or mixtures of stereoisomers. The compound of the present invention has significant activity of antagonizing histamine H1 receptor, and has lower anti-M-choline side effects and lower hERG toxicity,

##STR00001##

Wherein the group is defined as described in the specification.

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##

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 invention provides a method of treating one or more sodium channel related diseases or disorders in an individual, including related symptoms. The method comprises administering to the individual a tetrahydropyridine derivative in an amount effective to treat sodium channel related diseases or disorders in individuals. These compounds are generally categorised as Ritalin related compounds. The present invention also provides compounds for use in the treatment of and also for use in the manufacture of a medicament for the treatment of sodium channel related diseases or disorders in an individual. A method is further provided for the preparation and isolation of the derivatives of the compound of the present invention.

The present invention provides a method of treating one or more sodium channel related diseases or disorders in an individual, including related symptoms. The method comprises administering to the individual a tetrahydropyridine derivative in an amount effective to treat sodium channel related diseases or disorders in individuals. These compounds are generally categorised as Ritalin related compounds. The present invention also provides compounds for use in the treatment of and also for use in the manufacture of a medicament for the treatment of sodium channel related diseases or disorders in an individual. A method is further provided for the preparation and isolation of the derivatives of the compound of the present invention.