The present invention relates to a compound of formula (Ia), or a pharmaceutically acceptable salt or hydrate thereof, wherein: the group X-Y is —NHSO.sub.2— or —SO.sub.2NH—; R.sub.1 is H or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, Cl and alkyl; R.sub.4 is selected from H, Cl and F; R.sub.5 is selected from H, alkyl, alkynyl, alkenyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, Cl, F, SO.sub.2-alkyl, SO.sub.2NR.sub.13R.sub.14, optionally substituted heteroaryl and alkyl; R.sub.8 is selected from H, alkyl, haloalkyl and halo; R.sub.9 is H, C.sub.1-C.sub.3-alkyl, or halo; R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an azepanyl group, wherein (a) said azepanyl group is substituted by one or more substituents, or (b) one or two carbons in said azepanyl group are replaced by a group selected from O, NH, S and CO, and said azepanyl group is optionally further substituted; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an azetidinyl, pyrrolidinyl or piperidinyl group wherein (a) said azetidinyl, pyrrolidinyl or piperidinyl group is substituted by one or more substituents, or (b) one or two carbons in said azetidinyl, pyrrolidinyl or piperidinyl group are replaced by a group selected from NH, S and CO; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an 8, 9 or 10-membered bicyclic heterocycloalkyl group, wherein one or two carbons in the bicyclic heterocycloalkyl ring are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic heterocycloalkyl group is optionally substituted; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form a 6 to 12-membered bicyclic group containing a spirocyclic carbon atom, wherein one or two carbons in the bicyclic group are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic group is optionally substituted, or said bicyclic group is optionally fused to a 5 or 6-membered aryl or heteroaryl group; R.sub.13 and R.sub.14 are each independently H or alkyl. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

##STR00001##

The present invention relates to a compound of formula (Ia), or a pharmaceutically acceptable salt or hydrate thereof, wherein: the group X-Y is —NHSO.sub.2— or —SO.sub.2NH—; R.sub.1 is H or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, Cl and alkyl; R.sub.4 is selected from H, Cl and F; R.sub.5 is selected from H, alkyl, alkynyl, alkenyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, Cl, F, SO.sub.2-alkyl, SO.sub.2NR.sub.13R.sub.14, optionally substituted heteroaryl and alkyl; R.sub.8 is selected from H, alkyl, haloalkyl and halo; R.sub.9 is H, C.sub.1-C.sub.3-alkyl, or halo; R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an azepanyl group, wherein (a) said azepanyl group is substituted by one or more substituents, or (b) one or two carbons in said azepanyl group are replaced by a group selected from O, NH, S and CO, and said azepanyl group is optionally further substituted; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an azetidinyl, pyrrolidinyl or piperidinyl group wherein (a) said azetidinyl, pyrrolidinyl or piperidinyl group is substituted by one or more substituents, or (b) one or two carbons in said azetidinyl, pyrrolidinyl or piperidinyl group are replaced by a group selected from NH, S and CO; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form an 8, 9 or 10-membered bicyclic heterocycloalkyl group, wherein one or two carbons in the bicyclic heterocycloalkyl ring are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic heterocycloalkyl group is optionally substituted; or R.sub.10 and R.sub.11, together with the nitrogen to which they are attached, form a 6 to 12-membered bicyclic group containing a spirocyclic carbon atom, wherein one or two carbons in the bicyclic group are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic group is optionally substituted, or said bicyclic group is optionally fused to a 5 or 6-membered aryl or heteroaryl group; R.sub.13 and R.sub.14 are each independently H or alkyl. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

##STR00001##

Described herein is a perfluorinated aminoolefin compound of general formula (I): CFY═CXN(R.sub.f)CF.sub.2R.sub.f′ where: (a) R.sub.f and R.sub.f′ are (i) independently selected from a linear or branched perfluoroalkyl group having 1-8 carbon atoms, optionally comprising at least one catenated O or N atom, or (ii) bonded together to form a perfluorinated ring structure having 4-8 ring carbon atoms, optionally comprising at least one catenated O atom; and (b) X and Y are (i) independently selected from a perfluoroalkyl group having 1-4 carbon atoms, or (ii) bonded together to form a perfluorinated ring structure having 5-6 ring carbon atoms. Such compounds may be used in heat transfer, foam blowing or immersion cooling applications, or as a working fluid in a Rankine cycle, a coating or lubricant, or as a dielectric fluid. Also disclosed herein is a method for making such compounds.

Described herein is a perfluorinated aminoolefin compound of general formula (I): CFY═CXN(R.sub.f)CF.sub.2R.sub.f′ where: (a) R.sub.f and R.sub.f′ are (i) independently selected from a linear or branched perfluoroalkyl group having 1-8 carbon atoms, optionally comprising at least one catenated O or N atom, or (ii) bonded together to form a perfluorinated ring structure having 4-8 ring carbon atoms, optionally comprising at least one catenated O atom; and (b) X and Y are (i) independently selected from a perfluoroalkyl group having 1-4 carbon atoms, or (ii) bonded together to form a perfluorinated ring structure having 5-6 ring carbon atoms. Such compounds may be used in heat transfer, foam blowing or immersion cooling applications, or as a working fluid in a Rankine cycle, a coating or lubricant, or as a dielectric fluid. Also disclosed herein is a method for making such compounds.

Provided are compounds that inhibit ferroptosis activity, or modulate or inhibit a disease associated with ferroptosis dysregulation, such as neuropathy, ischemia reperfusion injury, acute kidney failure and cancer, 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.

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

The present inventors found cyclic peptide compounds that interact with Ras, and non-natural amino acids useful for the production of the cyclic peptide compounds. The inventors also found that the cyclic peptide compounds inhibit the binding between Ras and SOS. In addition, the inventors found specific non-natural amino acids contained in the cyclic peptide compounds and methods for production thereof.

The present inventors found cyclic peptide compounds that interact with Ras, and non-natural amino acids useful for the production of the cyclic peptide compounds. The inventors also found that the cyclic peptide compounds inhibit the binding between Ras and SOS. In addition, the inventors found specific non-natural amino acids contained in the cyclic peptide compounds and methods for production thereof.

A compound of Formula (I) or a pharmaceutically acceptable salt thereof is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.

##STR00001##

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.