Imidazole based LXR modulators
Granted: April 7, 2015
Patent Number:
9000022
Methods of using compounds of the invention, such as compounds of Formulae IIa, IIb, IIc, or IId and pharmaceutically acceptable salts thereof are disclosed. The compounds are useful in treating, preventing, inhibiting or ameliorating the symptoms of a disease or disorder that is modulated or otherwise affected by nuclear receptor activity, or in which nuclear receptor activity is implicated.
Methods of treating cancer using pyridopyrimidinone inhibitors of PI3K and mTOR in combination with autophagy inhibitors
Granted: December 2, 2014
Patent Number:
8901137
The invention provides compounds of Formula I: that inhibit the PI3Ks and mTOR that are useful in the treatment of cancer in humans when used in combination with autophagy inhibitors.
Phosphatidylinositol 3-kinase inhibitors and methods of their use
Granted: November 18, 2014
Patent Number:
8889664
The present invention comprises small molecule inhibitors of phosphatidylinositol 3-kinase (PI3K), which is associated with a number of malignancies such as ovarian cancer, cervical cancer, breast cancer, colon cancer, rectal cancer, and glioblastomas, among others. Accordingly, the compounds of the present invention are useful for treating, preventing, and/or inhibiting these diseases.
(L)-malate salt of N-(4-{[6,7-bis(methyloxy) quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
Granted: November 4, 2014
Patent Number:
8877776
Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N?-(4-fluorophenyl)cyclopropane -1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N?-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of…
TGR5 agonists
Granted: September 30, 2014
Patent Number:
8846739
TGR5 agonists of structural formula VIII(Q), wherein X, R1, R2, and R5 are defined in the specification, pharmaceutically acceptable salts thereof, compositions thereof, and use of the compounds and compositions for treating diseases. The invention also comprises use of the compounds in and for the manufacture of medicaments, particularly for treating diseases.
Synergistic effects between sphingosine-1-phosphate receptor antagonists and antimicrotubule agents
Granted: August 12, 2014
Patent Number:
8802692
This invention is based on the discovery that the administration of a sphingosine-1-phosphate receptor antagonist (S1P) and at least one chemotherapeutic agent selected from the the group of antimicrotubule agents provides an unexpectedly superior treatment for cancer. Antimicrobial agents such as the taxane compounds are known in the art, for example, paclitaxel (available as TAXOL® from Bristol-Myers Squibb, Princeton, N.J.), docetaxel (available as TAXOTERE® from Sanofi-aventis,…
Inhibitors of the hedgehog pathway
Granted: August 5, 2014
Patent Number:
8796294
The present invention is directed to a compound of Formula I or a single isomer thereof; where the compound is optionally as a pharmaceutically acceptable salt, hydrate, solvate or combination thereof, in addition to methods of preparing a Compound of Formula I, and methods of using a Compound of Formula I to treat cancer.
Acetanilide sphingosine-1-phosphate receptor antagonists
Granted: July 29, 2014
Patent Number:
8791102
This disclosure relates to sphingosine-1-phosphate (S1P) receptor antagonists, compositions comprising the S1P receptor antagonists and methods for using and processes for making the S1P receptor antagonists. In particular, this disclosure relates to sphingosine-1-phosphate 1 (S1P1) receptor antagonists, compositions comprising the S1P1 receptor antagonist and methods for using the S1P1 receptor antagonist, such as in the treatment of cancer, and processes for making the S1P1 receptor…
Triazole and imidazole derivatives for use as TGR5 agonists in the treatment of diabetes and obesity
Granted: July 22, 2014
Patent Number:
8785488
The present invention comprises TGR5 agonists of structural formula I, wherein X, R1, R2, and R5 are defined herein, as well as N-oxides of them and pharmaceutically acceptable salts thereof. The invention further comprises composition comprising the compounds, N-oxides, and/or pharmaceutically acceptable salts thereof. The invention also comprises use of the compounds and compositions for treating diseases in which TGR5 is a mediator or is implicated. The invention also comprises…
SCDs as modifiers of the p53 pathway and methods of use
Granted: July 8, 2014
Patent Number:
8771942
Human SCD genes are identified as modulators of the p53 pathway, and thus are therapeutic targets for disorders associated with defective p53 function. Methods for identifying modulators of p53, comprising screening for agents that modulate the activity of SCD are provided.
CDK9 as modifier of the IGF pathway and methods of use
Granted: June 24, 2014
Patent Number:
8758994
Human CDK9 genes are identified as modulators of the IGF pathway, and thus are therapeutic targets for disorders associated with defective IGF function. Methods for identifying modulators of IGF, comprising screening for agents that modulate the activity of CDK9 are provided.
Inhibitors of the hedgehog pathway
Granted: June 17, 2014
Patent Number:
8754092
The present invention is directed to a compound of Formula I or a single isomer thereof; where the compound is optionally as a pharmaceutically acceptable salt, hydrate, solvate or combination thereof, in addition to methods of preparing a Compound of Formula I, and methods of using a Compound of Formula I to treat cancer.
Quinazolinone modulators of nuclear receptors
Granted: June 10, 2014
Patent Number:
8748440
Compounds, pharmaceutical compositions and methods for modulating the activity of nuclear receptors are provided. In particular, quinazolinones are provided for modulating the activity of farnesoid X receptor (FXR) and/or orphan nuclear receptors.
Pyrazole kinase modulators and methods of use
Granted: April 29, 2014
Patent Number:
8710038
The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinases. Methods of using the compounds and pharmaceutical compositions thereof to treat kinase-dependent diseases and conditions are also an aspect of the invention.
Modulators of LXR
Granted: April 22, 2014
Patent Number:
8703805
Compounds of the invention, such as compounds of Formulae Ia, Ib, Ic, or Id and pharmaceutically acceptable salts, isomers, and prodrugs thereof, which are useful as modulators of the activity of liver X receptors, where R1, R2, R21, R3, and G are defined herein. Pharmaceutical compositions containing the compounds and methods of using the compounds are also disclosed.
Raf modulators and methods of use
Granted: April 15, 2014
Patent Number:
8697737
The present invention relates to compounds of the Formula I, wherein G, A, X1, X2, X3, Z, E, Y, and X are defined herein. The compounds modulate protein kinase enzymatic activity to modulate cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinases, particularly Raf. Methods of using and preparing the compounds, and pharmaceutical compositions thereof, to treat…
EEF2K as modifiers of the PTEN/AKT pathway and methods of use
Granted: March 25, 2014
Patent Number:
8679763
Human EEF2K genes are identified as modulators of the PTEN/AKT pathway and thus are therapeutic targets for disorders associated with defective PTEN/AKT function. Methods for identifying modulators of PTEN/AKT comprising screening for agents that modulate the activity of EEF2K are provided.
Crystalline Forms on N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]-quinolin-4-yl}oxy)phenyl]-N?-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
Granted: March 18, 2014
Patent Number:
8673912
This invention relates to three crystalline forms of N-[3-fluoro-4-((6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl|oxy)phenyl]-N?-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide. Compound (I), designated as Form A, Form B, and Form C. The invention provides methods for treatment of cancer by exploiting the modulation of protein kinase activity. The invention also provides pharmaceutical compositions containing a crystalline form of Compound (I) and a pharmaceutically…
Benzoxazepines as inhibitors of PI3K/mTOR and methods of their use and manufacture
Granted: February 11, 2014
Patent Number:
8648066
The invention is directed to Compounds of Formula I: and pharmaceutically acceptable salts or solvates thereof, as well as methods of making and using the compounds.
1-phenylpyrrole derivatives
Granted: February 4, 2014
Patent Number:
8642640
The present invention comprises a compound for the prevention and/or treatment of cardiovascular diseases, nephropathy, fibrosis, primary aldosteronism or edema. The compound is of the following general formula (I): wherein R1 represents a C1-C3 alkyl group; R2 represents a hydroxy-C1-C4 alkyl group and the like; R3 represents a halogeno group, a halogeno-C1-C3 alkyl group and the like; R4 represents a hydrogen atom, a halogeno group and the like, —R5 represents a sulfamoyl group or a…
