Triazole agonists of the APJ receptor

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

Compounds for use in preparing heterocyclic triazole agonists of the APJ receptor

Compounds of Formula V, salts thereof, tautomers thereof, and salts of the tautomers have the following structure and are useful compounds in preparing small molecule agonists of the APJ Receptor: where the definitions of the variables are provided herein.

HIGH AFFINITY ANTIBODIES TARGETING TAU PHOSPHORYLATED AT SERINE 413

Provided herein are high affinity antibodies or antigen binding fragments thereof that specifically bind to human tau-pS413. Also provided are compositions, kits, methods, and uses involving such antibodies or antigen binding fragments thereof.

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: 2. The compound of or the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer claim 1 , wherein Ris an unsubstituted pyridyl or is a pyridyl substituted with 1 or 2 Rsubstituents.6. The compound of or the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer claim 1 , wherein Ris a phenyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , isoxazolyl claim 1 , indolyl claim 1 , naphthyl claim 1 , or pyridinyl any of which may be unsubstituted or substituted with 1 claim 1 , 2 claim 1 , or 3 Rsubstituents.7. The compound of or the salt thereof claim 6 , the tautomer thereof claim 6 , or the salt of the tautomer claim 6 , wherein Ris in each instance independently selected from CH claim 6 , —F claim 6 , —Cl claim 6 , —Br claim 6 , —CN claim 6 , —CF claim 6 , —OCH claim 6 , —OCHF claim 6 , —OCHCH claim 6 , —C(═O)OCH claim 6 , —C(═O)CH claim 6 , or N(CH).9. The compound of or the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer claim 1 , wherein Ris a phenyl substituted with 1 or 2 Rsubstituents.10. The compound of or the salt thereof claim 9 , the tautomer thereof claim 9 , or the salt of the tautomer claim 9 , wherein the 1 or 2 Rsubstituents are —O—(C-Calkyl) groups.11. The compound of or the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer claim 1 , wherein Q is selected from pyrimidinyl claim 1 , pyridyl claim 1 , isoxazolyl claim 1 , thiazolyl claim 1 , imidazolyl claim 1 , phenyl claim 1 , tetrahydropyrimidinonyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclohexyl claim 1 , morpholinyl claim 1 , pyrrolidinyl claim 1 , pyrazinyl claim ...

Nitrogen-containing heterocyclyl ketones and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

PLASMA KALLIKREIN INHIBITORS

The present invention provides a compound of Formula I and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Nitrogen-Containing heterocyclyl ketones and methods of use

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Indole/Benzimidazole Compounds as mTOR Kinase Inhibitors

The present invention provides compounds that are kinase inhibitors, specifically PIK kinase inhibitors, more specifically, mTOR inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of kinases, specifically PIK kinase inhibitors, more specifically, mTOR such as cancer. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

Triazole furan compounds as agonists of the APJ receptor

Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula (I) and Formula (II) have the following structures: (I); (II). Intermediates (V) are also claimed.

PYRIMIDINE COMPOUNDS THAT INHIBIT ANAPLASTIC LYMPHOMA KINASE

Compounds of Formula I are useful inhibitors of anaplastic lymphoma kinase. Compounds of Formula I have the following structure: 2. The compound of claim 1 , wherein p is 2.3. The compound of claim 1 , wherein r is 1.4. The compound of claim 1 , wherein V is absent.5. The compound of claim 1 , wherein V is —O—.6. The compound of claim 1 , wherein V is —CH—.7. The compound of claim 1 , wherein X is —CH—.8. The compound of claim 1 , wherein X is —O—.9. The compound of claim 1 , wherein X is —S—.10. The compound of claim 1 , wherein X is —N(H)—.11. The compound of claim 1 , wherein q is 0.12. The compound of claim 1 , wherein q is 1 and Rand R are independently selected from —H claim 1 , —CH claim 1 , or Rand R claim 1 , when taken together claim 1 , represent a ═O.16. The compound of claim 13 , wherein Rand Rare independently selected from —H or —CH.17. The compound of claim 16 , wherein Rand Rare both —H.18. The compound of claim 13 , wherein Rand R are independently selected from —H or —CH.19. The compound of claim 18 , wherein Rand R are both —H.20. The compound of claim 13 , wherein Ris selected from —H or —CH.21. The compound of claim 20 , wherein Ris —H.22. The compound of claim 13 , wherein Ris selected from —H or —CH.23. The compound of claim 22 , wherein Ris —H24. The compound of claim 1 , wherein r is 0.25. The compound of claim 24 , wherein q is 0.26. The compound of claim 1 , wherein Z is an unsubstituted or substituted phenyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , naphthyl claim 1 , indanyl claim 1 , 2 claim 1 ,3-dihydrobenzofuranyl claim 1 , benzofuranyl claim 1 , benzothiophenyl claim 1 , indolyl claim 1 , thiazolyl claim 1 , imidazolyl claim 1 , imidazo[1 claim 1 ,2-a]pyridyl claim 1 , quinolinyl claim 1 , isoquinolinyl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4 claim 1 ,4a claim 1 ,8a-hexahydroquinolinyl claim 1 , 2 claim 1 ,3-dihydrobenzo[b][1 claim 1 ,4]dioxinyl claim 1 , pyridazinyl claim 1 , pyrazinyl claim 1 , indazolyl claim 1 , ...

Triazole agonists of the APJ receptor

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

BENZIMIDAZOLE AND AZABENZIMIDAZOLE COMPOUNDS THAT INHIBIT ANAPLASTIC LYMPHOMA KINASE

Compounds of Formula (I) are useful inhibitors of anaplastic lymphoma kinase. Compounds of Formula (I) have the following structure: where the definitions of the variables are provided herein.

PLASMA KALLIKREIN INHIBITORS

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Triazole pyridyl compounds as agonists of the APJ receptor

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the structures where the definitions of the variables are provided herein.

HIGH AFFINITY ANTIBODIES TARGETING TAU PHOSPHORYLATED AT SERINE 413

Provided herein are high affinity antibodies or antigen binding fragments thereof that specifically bind to human tau-pS413. Also provided are compositions, kits, methods, and uses involving such antibodies or antigen binding fragments thereof.

HIGH AFFINITY ANTIBODIES TARGETING TAU PHOSPHORYLATED AT SERINE 413

Provided herein are high affinity antibodies or antigen binding fragments thereof that specifically bind to human tau-pS413. Also provided are compositions, kits, methods, and uses involving such antibodies or antigen binding fragments thereof.

SPIRO-TRICYCLIC RING COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, T1, T2, W, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

Pyrimidine compounds that inhibit anaplastic lymphoma kinase

The present invention describes pyrimidine compounds of Formula I that are useful as anaplastic lymphoma kinase inhibitors, pharmaceutically acceptable compositions thereof, and methods of using the same.

Spiro-tricyclic ring compounds as beta-secretase modulators and methods of use

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, T1, T2, W, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

Generative Modeling Leveraging Deep Learning for Antibody Affinity Tuning

A computer-implemented method is disclosed for candidate antibody exploration. The method includes receiving sequence reads from a sequencing system, wherein each sequence read comprises a target gene for expressing a candidate antibody, wherein each sequence read is associated with a binding affinity to a target antigen. The method includes generating a sequence representation for each sequence read, representing the amino acid sequences of the sequence read. The method includes training a binding affinity prediction model with the sequence representations and the binding affinities. The method includes generating a synthetic candidate sequence read that is different from the sequence reads. The method includes generating a sequence representation for the synthetic candidate sequence read. The method includes determining a binging affinity prediction for the synthetic candidate sequence read by applying the binding affinity prediction model to the sequence representation for the synthetic candidate sequence read.

Heteroaryl-substituted triazoles as APJ receptor agonists

Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

Heteroaryl Compounds as PIKK Inhibitors

The present invention provides compounds that are PIKK inhibitors, more specifically, mTOR and/or PI3K kinase inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of kinases, specifically PI3 kinases, more specifically, mTOR and/or PI3K, such as cancer. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

AFFINITY MATURED ANTI-LAP ANTIBODIES AND USES THEREOF

Provided herein are anti-LAP antibodies (e.g., recombinant humanized, chimeric, and human anti-LAP antibodies) or antigen binding fragments thereof which have therapeutically beneficial properties, such as binding specifically to LAP-TGFβ1 on cells but not to LAP-TGFβ1 in extracellular matrix, as well as compositions including the same. Also provided are uses of these antibodies or antigen binding fragments in therapeutic applications, such as in the treatment of cancer, and diagnostic applications.

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: 2. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the stereoisomer of any of the foregoing claim 1 , or the mixture thereof claim 1 , wherein Ris an unsubstituted pyridyl or is a pyridyl substituted with 1 or 2 Rsubstituents.6. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the stereoisomer of any of the foregoing claim 1 , or the mixture thereof claim 1 , wherein Ris —H.7. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the stereoisomer of any of the foregoing claim 1 , or the mixture thereof claim 1 , wherein Ris a phenyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , isoxazolyl claim 1 , indolyl claim 1 , naphthyl claim 1 , or pyridinyl any of which may be unsubstituted or substituted with 1 claim 1 , 2 claim 1 , or 3 Rsubstituents.8. The compound of or the pharmaceutically acceptable salt thereof claim 7 , the stereoisomer of any of the foregoing claim 7 , or the mixture thereof claim 7 , wherein Ris in each instance independently selected from —CH claim 7 , —F claim 7 , —Cl claim 7 , —Br claim 7 , —CN claim 7 , —CF claim 7 , —OCH claim 7 , —OCHF claim 7 , —OCHCH claim 7 , —C(═O)OCH claim 7 , —C(═O)CH claim 7 , or —N(CH).10. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the stereoisomer of any of the foregoing claim 1 , or the mixture thereof claim 1 , wherein Ris a phenyl substituted with 1 or 2 Rsubstituents.11. The compound of or the pharmaceutically acceptable salt thereof claim 10 , the stereoisomer of any of the foregoing claim 10 , or the mixture thereof claim 10 , wherein the 1 or 2 Rsubstituents are —O—(C-Calkyl) groups.12. The compound of or the ...

High affinity antibodies targeting tau phosphorylated at serine 413

Provided herein are high affinity antibodies or antigen binding fragments thereof that specifically bind to human tau-pS413. Also provided are compositions, kits, methods, and uses involving such antibodies or antigen binding fragments thereof.

COMPOUNDS FOR USE IN PREPARING HETEROCYCLIC TRIAZOLE AGONISTS OF THE APJ RECEPTOR

Compounds of Formula V, salts thereof, tautomers thereof, and salts of the tautomers have the following structure and are useful compounds in preparing small molecule agonists of the APJ Receptor: where the definitions of the variables are provided herein.

Triazole agonists of the APJ receptor

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

Triazole agonists of the APJ receptor

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

Intermediates for preparing triazole agonists of the APJ receptor

Compounds of Formula VII, salts thereof, tautomers thereof, and salts of the tautomers are useful intermediates in the synthesis of agonists of the APJ Receptor. Compounds of Formula VII have the following structure: where the definitions of the variables are provided herein.

BENZIMIDAZOLE AND AZABENZIMIDAZOLE COMPOUNDS THAT INHIBIT ANAPLASTIC LYMPHOMA KINASE

Compounds of Formula (I) are useful inhibitors of anaplastic lymphoma kinase. Compounds of Formula (I) have the following structure: where the definitions of the variables are provided herein. 2. The compound of claim 1 , wherein X is N claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , tautomer thereof claim 1 , a pharmaceutically acceptable salt of the tautomer claim 1 , or a stereoisomer of any of the foregoing.3. The compound of claim 1 , wherein X is CR claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , tautomer thereof claim 1 , a pharmaceutically acceptable salt of the tautomer claim 1 , or a stereoisomer of any of the foregoing.4. The compound of claim 3 , wherein Ris —H claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , tautomer thereof claim 3 , a pharmaceutically acceptable salt of the tautomer claim 3 , or a stereoisomer of any of the foregoing.5. The compound of claim 1 , wherein Ris —H claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , tautomer thereof claim 1 , a pharmaceutically acceptable salt of the tautomer claim 1 , or a stereoisomer of any of the foregoing.6. The compound of claim 1 , wherein Z is selected from —OMe or —NH-cyclohexyl; or an unsubstituted or substituted phenyl claim 1 , pyridyl claim 1 , benzothiophenyl claim 1 , thiazolyl claim 1 , pyradizinyl claim 1 , pyrimidinyl claim 1 , indolyl claim 1 , cyclohexyl claim 1 , morpholinyl claim 1 , pyrrolidinyl claim 1 , piperazinyl claim 1 , or piperidinyl group claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , tautomer thereof claim 1 , a pharmaceutically acceptable salt of the tautomer claim 1 , or a stereoisomer of any of the foregoing.7. The compound of claim 1 , wherein Z is an unsubstituted or substituted phenyl claim 1 , pyridyl claim 1 , benzothiophenyl claim 1 , thiazolyl claim 1 , pyradizinyl claim 1 , pyrimidinyl claim 1 , indolyl claim 1 , cyclohexyl claim 1 , morpholinyl claim 1 , pyrrolidinyl claim 1 , ...

Spiro-tetracyclic ring compounds as beta-secretase modulators and methods of use

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and other related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, R2, R7, X and Y of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

Compounds that inhibit MCL-1 protein

Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

PLASMA KALLIKREIN INHIBITORS

The present invention provides a compound of formula I and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Benzimidazole and azabenzimidazole compounds that inhibit anaplastic lymphoma kinase

Compounds of Formula (I) are useful inhibitors of anaplastic lymphoma kinase. Compounds of Formula (I) have the following structure: where the definitions of the variables are provided herein.

Heterocyclic triazole compounds as agonists of the APJ receptor

Compounds of Formula I and Formula II, pharmaceutically acceptable salts thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

SPIRO-TETRACYCLIC RING COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and other related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, R2, R7, X and Y of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: 2. The compound of claim 1 , the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer claim 1 , wherein Q′ is selected from a pyridinyl claim 1 , pyrimidinyl claim 1 , or pyrazinyl group that is unsubstituted or is substituted with 1 claim 1 , or 2 Rsubstituents.5. The compound of claim 4 , the salt thereof claim 4 , the tautomer thereof claim 4 , or the salt of the tautomer claim 4 , wherein R is a —CH6. The compound of claim 5 , the salt thereof claim 5 , the tautomer thereof claim 5 , or the salt of the tautomer claim 5 , wherein Ris a —C-Calkyl7. The compound of claim 6 , the salt thereof claim 6 , the tautomer thereof claim 6 , or the salt of the tautomer claim 6 , wherein R is a —CH8. The compound of claim 5 , the salt thereof claim 5 , the tautomer thereof claim 5 , or the salt of the tautomer claim 5 , wherein Ris a —O—(C-Calkyl).9. The compound of claim 8 , the salt thereof claim 8 , the tautomer thereof claim 8 , or the salt of the tautomer claim 8 , wherein Ris selected from —O—CH claim 8 , —O—CHCH claim 8 , or —O—CH(CH).10. The compound of claim 1 , the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer claim 1 , wherein R is a —CH11. The compound of claim 1 , the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer claim 1 , wherein Ris a —C-Calkyl12. The compound of claim 11 , the salt thereof claim 11 , the tautomer thereof claim 11 , or the salt of the tautomer claim 11 , wherein R is a —CH13. The compound of claim 1 , the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer claim 1 , wherein Ris a —O—(C-Calkyl).14. The compound of ...

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: 1. A compound or a pharmaceutically acceptable salt thereof , wherein the compound is(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(6-methoxy-2-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide;(2S,3R)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-3-(5-methyl-2-pyrimidinyl)-2-butanesulfonamide;(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide;(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-hydroxy-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide;(1S,2R)-1-(5-chloro-2-pyrimidinyl)-N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-2-propanesulfonamide;(1S,2R)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrazinyl)-2-propanesulfonamide;(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-hydroxy-1-(5-methyl-2-pyrazinyl)-2-propanesulfonamide;(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide;(2S,3R)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-3-(5-methyl-2-pyrimidinyl)-2-butanesulfonamide;(1R,2S)-1-(5-chloro-2-pyrimidinyl)-N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-2-propanesulfonamide;(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide;(1S,2R)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrazinyl)-2- ...

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: 2. The method of claim 1 , wherein the cardiovascular condition is heart failure.3. The method of claim 1 , wherein the cardiovascular condition is heart failure with reduced ejection fraction.4. The method of claim 1 , wherein the cardiovascular condition is heart failure with preserved ejection fraction.5. The method of claim 1 , wherein the cardiovascular condition is hypertension.6. The method of claim 1 , wherein the method includes administering at least one additional therapeutic agent to the subject claim 1 , wherein the additional therapeutic agent is selected from an α-blocker claim 1 , a β-blocker claim 1 , an angiotensin converting enzyme (ACE) inhibitor claim 1 , an angiotensin-receptor blocker (ARB) claim 1 , a calcium channel blocker claim 1 , a diuretic claim 1 , an inhibitor of the funny current claim 1 , a myosin activator claim 1 , or a neutral endopeptidase (NEP) inhibitor.7. The method of claim 1 , wherein the method includes administering at least one additional therapeutic agent to the subject claim 1 , wherein the additional therapeutic agent is selected from an angiotensin converting enzyme (ACE) inhibitor or an angiotensin-receptor blocker (ARB).10. The method of claim 1 , wherein Ris an unsubstituted pyridyl or is a pyridyl substituted with 1 or 2 Rsubstituents.13. The method of claim 1 , wherein Ris —H.14. The method of claim 1 , wherein Ris a phenyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , isoxazolyl claim 1 , indolyl claim 1 , naphthyl claim 1 , or pyridinyl any of which may be unsubstituted or substituted with 1 claim 1 , 2 claim 1 , or 3 Rsubstituents.16. The method of claim 1 , wherein Ris a phenyl substituted with 1 or 2 ...

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: 2. The method of claim 1 , wherein the condition is obesity or diabetes.3. The method of claim 1 , wherein the condition is diabetic nephropathy or chronic kidney disease.4. The method of claim 1 , wherein Ris an unsubstituted pyridyl or is a pyridyl substituted with 1 or 2 Rsubstituents.7. The method of claim 1 , wherein Ris —H.8. The method of claim 1 , wherein Ris a phenyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , isoxazolyl claim 1 , indolyl claim 1 , naphthyl claim 1 , or pyridinyl any of which may be unsubstituted or substituted with 1 claim 1 , 2 claim 1 , or 3 Rsubstituents.10. The method of claim 1 , wherein Ris a phenyl substituted with 1 or 2 Rsubstituents claim 1 , wherein the 1 or 2 Rsubstituents are —O—(C-Calkyl) groups.11. The method of claim 1 , wherein Q is selected from pyrimidinyl claim 1 , pyridyl claim 1 , isoxazolyl claim 1 , thiazolyl claim 1 , imidazolyl claim 1 , phenyl claim 1 , tetrahydropyrimidinonyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclohexyl claim 1 , morpholinyl claim 1 , pyrrolidinyl claim 1 , pyrazinyl claim 1 , imidazo[1 claim 1 ,2-a]pyridinyl claim 1 , pyrazolyl claim 1 , or oxetanyl any which may be unsubstituted or substituted with 1 claim 1 , 2 claim 1 , or 3 claim 1 , Rsubstituents.12. The method of claim 1 , wherein Q is a monocyclic heteroaryl group with 5 or 6 ring members containing 1 or 2 heteroatoms selected from N claim 1 , O claim 1 , or S and Q is unsubstituted or is substituted with 1 or 2 Rsubstituents.14. The method of claim 1 , wherein Ris a group of formula —(CRR)—(CRR)-Q.17. The method of claim 1 , wherein the compound is(1R,2S)-N-(4-(2,6-dimethoxyphenyl)-5-(6-methoxy-2-pyridinyl)-4H-1,2 ...

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: 2. The method of claim 1 , wherein cyclizing further comprises heating the compound of Formula V claim 1 , the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer in the presence of the acid or the base.3. The method of claim 2 , wherein heating the compound of Formula V claim 2 , the salt thereof claim 2 , the tautomer thereof claim 2 , or the salt of the tautomer comprises heating the compound to a temperature of from 50° C. to 100° C.4. The method of claim 2 , wherein heating the compound of Formula V claim 2 , the salt thereof claim 2 , the tautomer thereof claim 2 , or the salt of the tautomer comprises heating the compound to a temperature of from 60° C. to 85° C.5. The method of any one of claim 1 , wherein the cyclizing of the compound of Formula V claim 1 , the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer is performed in the presence of the base.6. The method of any one of claim 1 , wherein the base is a metal hydroxide.7. The method of claim 6 , wherein the metal hydroxide is selected from NaOH or LiOH.8. The method of claim 5 , wherein the cyclizing is carried out in an alcohol solvent.9. The method of claim 8 , wherein the alcohol is isopropanol.10. The method of any one of claim 1 , wherein cyclizing further comprises heating the compound of Formula V claim 1 , the salt thereof claim 1 , the tautomer thereof claim 1 , or the salt of the tautomer in the presence of the acid.11. The method of claim 10 , wherein the acid is selected from a sulfonic acid claim 10 , a carboxylic acid claim 10 , polyphosphoric acid claim 10 , phosphoric acid claim 10 , sulfuric acid claim 10 , or hydrochloric ...

Compounds that inhibit mcl-1 protein

Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

TRIAZOLE FURAN COMPOUNDS AS AGONISTS OF THE APJ RECEPTOR

Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula (I) and Formula (II) have the following structures: (I); (II). Intermediates (V) are also claimed. 2. (canceled)3. The compound of or or the pharmaceutically acceptable salt thereof , the tautomer thereof , the pharmaceutically acceptable salt of the tautomer , the stereoisomer of any of the foregoing , or the mixture thereof , wherein 10 is a an unsubstituted furan-2-yl or a furan-2-yl substituted with 1 or 2 Rsubstituents independently selected from —F , —Cl , —Br , —I , —C-Calkyl , —C-Chaloalkyl , —C-Cperhaloalkyl , or —(C-Calkyl)-O—(C-Calkyl).56-. (canceled)7. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the tautomer thereof claim 1 , the pharmaceutically acceptable salt of the tautomer claim 1 , the stereoisomer of any of the foregoing claim 1 , or the mixture thereof claim 1 , wherein Ris an unsubstituted furan-2-yl or a substituted furan-2-yl and Ris independently selected from CH claim 1 , —CHCH claim 1 , —C(CH) claim 1 , —CF claim 1 , —CHOCH claim 1 , or —Br.8. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the tautomer thereof claim 1 , the pharmaceutically acceptable salt of the tautomer claim 1 , the stereoisomer of any of the foregoing claim 1 , or the mixture thereof claim 1 , wherein Ris —H or is absent in the compounds of Formula II.9. (canceled)10. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the tautomer thereof claim 1 , the pharmaceutically acceptable salt of the tautomer claim 1 , the stereoisomer of any of the foregoing claim 1 , or the mixture thereof claim 1 , wherein Ris a phenyl claim 1 , pyridinyl claim 1 , pyrimidinyl claim 1 , naphthyl claim 1 , tetrahydropyranyl claim 1 , cyclohexyl claim 1 , ...

Triazole pyridyl compounds as agonists of the apj receptor

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, I or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the structures where the definitions of the variables are provided herein.

HETEROCYCLIC TRIAZOLE COMPOUNDS AS AGONISTS OF THE APJ RECEPTOR

Compounds of Formula I and Formula II, pharmaceutically acceptable salts thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: 2. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the tautomer thereof claim 1 , the pharmaceutically acceptable salt of the tautomer claim 1 , the stereoisomer of any of the foregoing claim 1 , or the mixture thereof claim 1 , wherein one of the following is true:{'sup': 1a', '1', '1a′, '1) two Rsubstituents on adjacent carbon atoms or on an adjacent carbon atom and an adjacent N atom of a 5- or 6-membered heterocyclic Rgroup join to form a 6 membered ring that may be saturated, partially saturated, or aromatic and may include 0, 1, or 2 N atoms and may further optionally be substituted with 1 or 2 Rsubstituents and may include an oxo substituent if the ring is not an aromatic ring; or'}{'sup': 1a', '1', '1a′, '2) two Rsubstituents on adjacent carbon atoms or on an adjacent carbon atom and an adjacent N atom of a 5- or 6-membered heterocyclic Rgroup join to form a 5 membered ring that may be saturated, partially saturated, or aromatic and may include 0, 1, or 2 heteroatoms selected from N, O, or S and may further optionally be substituted with 1 or 2 Rsubstituent and may include an oxo substituent if the ring is not an aromatic ring.'}4. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the stereoisomer of any of the foregoing claim 1 , or the mixture thereof claim 1 , wherein Ris selected from a straight or branched chain C-Calkyl group that is unsubstituted or is substituted with 1 claim 1 , 2 claim 1 , or 3 Rsubstituents.7. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the tautomer thereof claim 1 , the pharmaceutically acceptable salt of the tautomer claim 1 , the stereoisomer of ...

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: 2. The compound of or the pharmaceutically acceptable salt thereof claim 1 , wherein Ris an unsubstituted pyridyl or is a pyridyl substituted with 1 or 2 Rsubstituents.6. The compound of or the pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H.7. The compound of or the pharmaceutically acceptable salt thereof claim 1 , wherein Ris a phenyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , isoxazolyl claim 1 , indolyl claim 1 , or naphthyl any of which may be unsubstituted or substituted with 1 claim 1 , 2 claim 1 , or 3 Rsubstituents.8. The compound of or the pharmaceutically acceptable salt thereof claim 7 , wherein Ris in each instance independently selected from —CH claim 7 , —F claim 7 , —Cl claim 7 , —Br claim 7 , —CN claim 7 , —CF claim 7 , —OCH claim 7 , —OCHF claim 7 , —OCHCH claim 7 , —C(═O)OCH claim 7 , —C(═O)CH claim 7 , or —N(CH).10. The compound of or the pharmaceutically acceptable salt thereof claim 1 , wherein Ris a phenyl substituted with 1 or 2 Rsubstituents.11. The compound of or the pharmaceutically acceptable salt thereof claim 10 , wherein the 1 or 2 Rsubstituents are —O—(C-Calkyl) groups.12. The compound of or the pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from a group of formula —(CRR)-Q claim 1 , a group of formula —NH—(CRR)-Q claim 1 , a group of formula —(CRR)—C(═O)-Q claim 1 , a group of formula —(CRR)—(CRR)-Q claim 1 , a group of formula —(CR═CR)-Q claim 1 , or a group of formula -(heterocyclyl)-Q claim 1 , wherein the heterocyclyl of the -(heterocyclyl)-Q has 5 to 7 ring members of which 1 claim 1 , 2 claim 1 , or 3 are heteroatoms selected from N claim 1 , O claim 1 , or S and is unsubstituted ...

Affinity matured anti-lap antibodies and uses thereof

Provided herein are anti-LAP antibodies (e.g., recombinant humanized, chimeric, and human anti-LAP antibodies) or antigen binding fragments thereof which have therapeutically beneficial properties, such as binding specifically to LAP-TGFβ1 on cells but not to LAP-TGFβ1 in extracellular matrix, as well as compositions including the same. Also provided are uses of these antibodies or antigen binding fragments in therapeutic applications, such as in the treatment of cancer, and diagnostic applications.

Benzimidazole and azabenzimidazole compounds that inhibit anaplastic lymphoma kinase

Compounds of Formula (I) are useful inhibitors of anaplastic lymphoma kinase. Compounds of Formula (I) have the following structure: where the definitions of the variables are provided herein.

HIGH-AFFINITY ANTIBODIES DIRECTED TO TAU PHOSPHORYLATED AT SERINE 413

En el presente documento se proporcionan anticuerpos de alta afinidad o fragmentos de unión a antígeno de los mismos que se unen específicamente a tau-pS413 humana. También se proporcionan composiciones, kits, métodos y usos en los que están implicados tales anticuerpos o fragmentos de unión a antígeno de los mismos. Provided herein are high affinity antibodies or antigen-binding fragments thereof that specifically bind to human tau-pS413. Compositions, kits, methods, and uses involving such antibodies or antigen-binding fragments thereof are also provided.

High affinity antibodies targeting tau phosphorylated at serine 413

Provided herein are high affinity antibodies or antigen binding fragments thereof that specifically bind to human tau-pS413. Also provided are compositions, kits, methods, and uses involving such antibodies or antigen binding fragments thereof.

receptor triazole agonists apj.

Plasma kallikrein inhibitors

The present invention provides a compound of Formula (I), and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Triazole agonists of apj receptor

【課題】様々な心血管状態および他の状態を処置するために使用できる、ＡＰＪ（アンギオテンシン受容体様−１）受容体のアゴニストの提供。 【解決手段】化合物が下式で代表される複素環化合物である、化合物又は医薬として許容されるその塩。該化合物は、ピリジン環、１，２，４−トリアゾール環、及びピリミジン環又はピラジン環を含む。該化合物は、心不全等の心血管状態を処置するための医薬組成物として用いることができる。 【選択図】なし

Nitrogen-containing heterocyclyl ketones and their use as c-met inhibitors

Selected compounds defined by Formula I, II, III, IV or V are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases.

Benzimidazole and azabenzimidazole compounds that inhibit anaplastic lymphoma kinase

Compounds of Formula (I) are useful inhibitors of anaplastic lymphoma kinase. Compounds of Formula (I) have the following structure: where the definitions of the variables are provided herein.

Triazole agonists of the apj receptor

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures where the definitions of the variables are provided herein.

Spiro-tetracyclic ring compounds as betasecretase modulators and methods of use

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula (I); wherein A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , T 1 , T 2 , W, X, Y and Z of Formula (I) are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula (I).

Heterocyclic triazole compounds as agonists of the apj receptor

Compounds of Formula I and Formula II, pharmaceutically acceptable salts thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

Spiro-tetracyclic ring compounds as betasecretase modulators and methods of use

Spiro-tetracyclic ring compounds as beta-secretase modulators

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and other related conditions. In one embodiment, the compounds have a general Formula (I) wherein A1, A2, A3, A4, A5, A6, R2, R7, X and Y of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

Spiro-tetracyclic ring compounds as betasecretase modulators and methods of use.

La presente invención comprende una nueva clase de compuestos útiles para la modulación de la actividad de la enzima beta-secretasa y para el tratamiento de las enfermedades mediadas por la beta-secretasa, incluyendo la enfermedad de Alzheimer (AD) y las afecciones relacionadas. En una modalidad, los compuestos tienen una Fórmula I (Ver fórmula (I)) general en donde A1, A2, A3, A4, A5, A6, T1, T2, W, X, Y y Z de la Fórmula I se definen en la presente. La invención también incluye el uso de estos compuestos en composiciones farmacéuticas para el tratamiento, profiláctico o terapéutico, de trastornos y afecciones relacionadas con la actividad de la proteína beta-secretasa. Esos trastornos incluyen, por ejemplo, la enfermedad de Alzheimer, el déficit cognitivo, el deterioro cognitivo, la esquizofrenia y otras afecciones del sistema nervioso central relacionadas con y/o provocadas por la formación y/o deposición de placa en el cerebro. La invención comprende también otras modalidades de la Fórmula I, intermediarios y procesos útiles para la preparación de los compuestos de la Fórmula I.

Heteroaryl compounds as pikk inhibitors.

La presente invención proporciona compuestos que son inhibidores de PIKK, más específicamente, inhibidores de la cinasa mTOR y/o PI3Ka y, por lo tanto, son útiles para el tratamiento de enfermedades que se pueden tratar mediante la inhibición de cinasas, específicamente cinasas PI3, más específicamente, mTOR y/o PI3Ka, como el cáncer. También se proporcionan composiciones farmacéuticas que contienen tales compuestos y procesos para la preparación de tales compuestos.

Pyrimidine compounds that inhibit anaplastic lymphoma kinase

Compounds of Formula I are useful inhibitors of anaplastic lymphoma kinase. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

Heteroaryl compounds as pikk inhibitors

The present invention provides compounds that are PIKK inhibitors, more specifically, mTOR and/or PI3K.alpha. kinase inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of kinases, specifically PI3 kinases, more specifically, mTOR and/or PI3K.alpha., such as cancer. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

Plasma kallikrein inhibitors

The present invention provides a compound of Formula I and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Indole/benzimidazole compounds as mtor kinase inhibitors

The present invention provides compounds of formula (I) (see formula I) that are kinase inhibitors, specifically PIK kinase inhibitors, more specifically, mTOR inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of kinases, specifically PIK kinase inhibitors, more specifically, mTOR such as cancer. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

Il-2 muteins for treating autoimmune and inflammatory diseases

Provided herein are IL-2 muteins that bind to IL-2 receptor subunit but do not have measurable binding to IL-2 receptor subunit. Also provided are compositions, kits, methods, and uses involving such IL-2 muteins.

Generative modeling leveraging deep learning for antibody affinity tuning

A computer-implemented method is disclosed for candidate antibody exploration. The method includes receiving sequence reads from a sequencing system, wherein each sequence read comprises a target gene for expressing a candidate antibody, wherein each sequence read is associated with a binding affinity to a target antigen. The method includes generating a sequence representation for each sequence read, representing the amino acid sequences of the sequence read. The method includes training a binding affinity prediction model with the sequence representations and the binding affinities. The method includes generating a synthetic candidate sequence read that is different from the sequence reads. The method includes generating a sequence representation for the synthetic candidate sequence read. The method includes determining a binging affinity prediction for the synthetic candidate sequence read by applying the binding affinity prediction model to the sequence representation for the synthetic candidate sequence read.

Anticuerpos de alta afinidad dirigidos a tau fosforilada en la serina 413.

En el presente documento se proporcionan anticuerpos de alta afinidad o fragmentos de unión a antígeno de los mismos que se unen específicamente a tau-pS413 humana. También se proporcionan composiciones, kits, métodos y usos en los que están implicados tales anticuerpos o fragmentos de unión a antígeno de los mismos.

Plasma kallikrein inhibitors

The present invention provides a compound of Formula I and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Plasma kallikrein inhibitors

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Plasma kallikrein inhibitors

The present invention provides a compound of Formula Iand pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Triazole agonists of the apj receptor

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures where the definitions of the variables are provided herein.

Plasma kallikrein inhibitors

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Plasma kallikrein inhibitors

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Triazole furan compounds as agonists of the apj receptor

Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula (I) and Formula (II) have the following structures: (I); (II). Intermediates (V) are also claimed.

Αγωνιστες τριαζολης του υποδοχεα αρj

Ενώσεις του Τύπου Ι και του Τύπου II, φαρμακευτικώς αποδεκτό άλας αυτών, στερεοϊσομερή οποιουδήποτε από τα προηγούμενα, ή μίγματα αυτών είναι αγωνιστές του Υποδοχέα ΑΡJ και χρησιμοποιούνται στη θεραπευτική αντιμετώπιση καρδιαγγειακών και άλλων καταστάσεων. Ενώσεις του Τύπου Ι και του Τύπου II έχουν τις ακόλουθες δομές όπου παρέχονται στην παρούσα οι ορισμοί των μεταβλητών.

Plasma kallikrein inhibitors

The present invention provides a compound of Formula I and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Inhibidores de calicreina plasmatica.

La presente invención proporciona un compuesto de Fórmula I (ver Fórmula) I y composiciones farmacéuticas que comprenden uno o más de dichos compuestos, y métodos para usar dichos compuestos para tratamiento o prevención de uno o más estados de enfermedad que podrían beneficiarse de la inhibición de calicreína plasmática, que incluyen angioedema hereditario, uveítis, uveítis posterior, edema macular húmedo relacionado con la edad, edema macular diabético, retinopatía diabética y oclusión de la vena retiniana. Los compuestos son inhibidores selectivos de calicreína plasmática.

Plasma kallikrein inhibitors

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Plasma kallikrein inhibitors

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Anticuerpos de alta afinidad dirigidos a tau fosforilados en la serina 413

En el presente documento se proporcionan anticuerpos de alta afinidad o fragmentos de unión a antígeno de los mismos que se unen específicamente a tau-pS413 humana. También se proporcionan composiciones, kits, métodos y usos en los que están implicados tales anticuerpos o fragmentos de unión a antígeno de los mismos.

Anticuerpos de alta afinidad dirigidos a tau fosforilada en serina 413.

En el presente documento se proporcionan anticuerpos de alta afinidad o fragmentos de unión a antígeno de los mismos que se unen específicamente a tau-pS413 humana. También se proporcionan composiciones, kits, métodos y usos en los que están implicados tales anticuerpos o fragmentos de unión a antígeno de los mismos.

Inhibidores de la calicreina plasmatica.

La presente invención proporciona un compuesto de la fórmula (I) y composiciones farmacéuticas que comprenden uno o más de dichos compuestos y métodos para utilizar dichos compuestos para tratar o prevenir uno o más estados de enfermedad que podrían beneficiarse de la inhibición de la calicreína plasmática, incluyendo angioedema hereditario, uveítis, uveítis posterior, edema macular húmedo relacionado con la edad, edema macular diabético, retinopatía diabética y oclusión venosa retiniana. Los compuestos son inhibidores selectivos de la calicreína plasmática.

Inhibidores de la calicreina plasmatica.

La presente invención proporciona un compuesto de la Fórmula I (ver Fórmula) y composiciones farmacéuticas que comprende uno o más de tales compuestos, y métodos para usarse tales compuestos para tratamiento o prevención de uno o más estados patológicos que podrían beneficiarse de la inhibición de calicreína plasmática, incluyendo angioedema hereditario, uveítis, uveítis posterior, edema macular húmedo relacionado con la edad, edema macular diabético, retinopatía diabética y oclusión de la vena retiniana. Los compuestos son inhibidores selectivos de calicreína plasmática.

Plasma kallikrein inhibitors

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Il-2 muteins for treating cancer or infection

Provided herein are IL-2 muteins that bind to the IL-2 receptor β subunit but do not have measurable binding to the IL-2 receptor α subunit. Also provided are compositions, kits, methods, and uses involving such IL-2 muteins.

Il-2 muteins for treating autoimmune and inflammatory diseases

Provided herein are IL-2 muteins that bind to IL-2 receptor subunit but do not have measurable binding to IL-2 receptor subunit. Also provided are compositions, kits, methods, and uses involving such IL-2 muteins.

IL-2 muteins for treating autoimmune and inflammatory diseases

Provided herein are IL-2 muteins that bind to IL-2 receptor a subunit but do not have measurable binding to IL-2 receptor Psubunit. Also provided are compositions, kits, methods, and uses involving such IL-2 muteins.

Muteinas de il-2 para el tratamiento contra enfermedades autoinmunitarias e inflamatorias.

En el presente documento se proporcionan muteínas de IL-2 que se unen a la subunidad del receptor de IL-2, pero no tienen unión cuantificable a la subunidad del receptor de IL-2. También se proporcionan composiciones, kits, métodos y usos que implican dichas muteínas de IL-2.

Il-2 muteins for treating autoimmune and inflammatory diseases

Provided herein are IL-2 muteins that bind to IL-2 receptor subunit but do not have measurable binding to IL-2 receptor subunit. Also provided are compositions, kits, methods, and uses involving such IL-2 muteins.

Il-2 muteins for treating autoimmune and inflammatory diseases

Provided herein are IL-2 muteins that bind to IL-2 receptor subunit but do not have measurable binding to IL-2 receptor subunit. Also provided are compositions, kits, methods, and uses involving such IL-2 muteins.

Plasma kallikrein inhibitors

Plasma kallikrein inhibitors

Plasma kallikrein inhibitors

Il-2 muteins for treating cancer or infection

Provided herein are IL-2 muteins that bind to the IL-2 receptor β subunit but do not have measurable binding to the IL-2 receptor a subunit. Also provided are compositions, kits, methods, and uses involving such IL-2 muteins.

Inhibidores de calicreina plasmatica.

La presente invención proporciona un compuesto de la Fórmula I (ver Fórmula) y composiciones farmacéuticas que comprenden uno o más de dichos compuestos, y métodos para usar dichos compuestos para tratar o prevenir uno o más estados de enfermedad que podrían beneficiarse por la inhibición de la calicreína plasmática, incluyendo angioedema hereditario, uveítis, uveítis posterior, degeneración macular húmeda relacionada con la edad, edema macular diabético, retinopatía diabética y oclusión de la vena de la retina. Los compuestos son inhibidores selectivos de calicreína plasmática.

Plasma kallikrein inhibitors