Abstract: The present invention encompasses compounds of formula (I) wherein R1a, R1b, R2a, R2b, Z, R3 to R5, A, p, U, V, W, L and E have the meanings given in the claims and specification, their use as inhibitors of mutant Ras family proteins, pharmaceutical compositions and preparations containing such compounds and their use as medicaments/medical uses, especially as agents for treatment and/or prevention of oncological diseases.

Abstract: The disclosure provides methods of treating a patient having primary hyperoxaluria or idiopathic hyperoxaluria comprising administering a therapeutically effective amount of compound of the formula and pharmaceutically acceptable salts, solvates, and hydrates thereof to the patient. The variables, e.g. ring A, n, R, R3, R10, X, Y, and Z are defined herein. These compounds act as lactate dehydrogenase inhibitors and are useful inhibiting the conversion of glyoxylate to oxalate. When administered to a patient having a disease or disorder associated with elevated oxalate levels, such as PH type 1, type 2, or type 3 or idiopathic hyperoxaluria the compounds prevent or substantially reduce the amount and buildup of oxalate the patient's kidneys, bladder, urinary tract and other parts of the patient's body.

Abstract: The disclosure provides methods of treating a patient having primary hyperoxaluria or idiopathic hyperoxaluria comprising administering a therapeutically effective amound of compound of the formula and pharmaceutically acceptable salts, solvates, and hydrates thereof to the patient. The variables, e.g. ring A, n, R, R3, R10, X, Y, and Z are defined herein. These compounds act as lactate dehydrogenase inhibitors and are useful inhibiting the conversion of glyoxylate to oxalate. When administered to a patient having a disease or disorder associated with elevated oxalate levels, such as PH type 1, type 2, or type 3 or idiopathic hyperoxaluria the compounds prevent or substantially reduce the amount and buildup of oxalate the patient's kidneys, bladder, urinary tract and other parts of the patient's body.

Abstract: The present invention encompasses compounds of formula (I) wherein R1a, R1b, R2a, R2b, Z, R3 to R5, A, p, U, V and W have the meanings given in the claims and specification, their use as inhibitors of KRAS, pharmaceutical compositions and preparations containing such compounds and their use as medicaments/medical uses, especially as agents for treatment and/or prevention of oncological diseases.

Abstract: The present invention encompasses compounds of formula (I), wherein R1a, R1b, R2a, R2b, Z, R3, R5, A, U, V, W, L and E have the meanings given in the claims and specification, their use as inhibitors of mutant Ras family proteins, pharmaceutical compositions and preparations containing such compounds and their use as medicaments/medical uses, especially as agents for treatment and/or prevention of oncological diseases.

Abstract: Substituted N-heteroaryl sulfonamide compounds inhibit WDR5-MYC interactions, and the compounds and their pharmaceutical compositions are useful for treating disorders and conditions in a subject such as cancer cell proliferation.

Abstract: The present invention encompasses compounds of formula (I) wherein R1a, R1b, R2a, R2b, Z, R3 to R5, A, p, U, V, W, L and E have the meanings given in the claims and specification, their use as inhibitors of mutant Ras family proteins, pharmaceutical compositions and preparations containing such compounds and their use as medicaments/medical uses, especially as agents for treatment and/or prevention of oncological diseases.

Abstract: The disclosure provides methods of treating a patient having primary hyperoxaluria or idiopathic hyperoxaluria comprising administering a therapeutically effective amound of compound of the formula and pharmaceutically acceptable salts, solvates, and hydrates thereof to the patient. The variables, e.g. ring A, n, R, R3, R10, X, Y, and Z are defined herein. These compounds act as lactate dehydrogenase inhibitors and are useful inhibiting the conversion of glyoxylate to oxalate. When administered to a patient having a disease or disorder associated with elevated oxalate levels, such as PH type 1, type 2, or type 3 or idiopathic hyperoxaluria the compounds prevent or substantially reduce the amount and buildup of oxalate the patient's kidneys, bladder, urinary tract and other parts of the patient's body.

Abstract: Benzimidazole compounds that increase the rate of SOS-mediated nucleotide exchange on Ras by binding to a functionally relevant, chemically tractable pocket on the SOS protein, as part of the Ras:SOS:Ras complex.

Abstract: Embodiments of the presently-disclosed subject matter include activators of HssRS that induce endogenous heme biosynthesis by perturbing central metabolism. These molecules are toxic to fermenting S. aureus, including clinically relevant small colony variants (SCVs). The utility of targeting fermenting bacteria is exemplified by the fact that this compound prevents the emergence of antibiotic resistance, enhances phagocyte killing, and reduces S. aureus pathogenesis. This small molecule is a powerful tool not only for studying bacterial heme biosynthesis and central metabolism, but also establishes targeting of fermentation as a viable antibacterial strategy.

Abstract: A method for treating a microbial infection involves administering an effective amount of a compound of the formula: wherein R1 is H, alkyl, aryl, heteroaryl, R2 is H, halogen, alkyl, aryl, heteroaryl, R3 is H, hydroxyl, alkoxy, alkyl, aryl, heteroaryl, amino, amino sulfonyl, acetamide, R4 is H, hydroxyl, alkoxy, alkyl, aryl, heteroaryl, amino, amino sulfonyl, acetamide, R5 is H, hydroxyl, alkoxy, alkyl, aryl, heteroaryl, amino, amino sulfonyl, acetamide, R6 is H, hydroxyl, alkoxy, alkyl, aryl, heteroaryl, amino, amino sulfonyl, acetamide, R7 is H, hydroxyl, alkoxy, alkyl, aryl, heteroaryl, amino, amino sulfonyl, acetamide, R8 is —CR3, O, S, wherein R5 and R6, R7 and R6, R5 and R4, R4 and R3 can cyclize forming a 3-10 member ring comprising C, O, S, and/or N optionally substituted with one or more R3; and administering light therapy, such as a photodynamic therapy (PDT) light source.

Abstract: Embodiments of the presently-disclosed subject matter include activators of HssRS that induce endogenous heme biosynthesis by perturbing central metabolism. These molecules are toxic to fermenting S. aureus, including clinically relevant small colony variants (SCVs). The utility of targeting fermenting bacteria is exemplified by the fact that this compound prevents the emergence of antibiotic resistance, enhances phagocyte killing, and reduces S. aureus pathogenesis. This small molecule is a powerful tool not only for studying bacterial heme biosynthesis and central metabolism, but also establishes targeting of fermentation as a viable antibacterial strategy.

Abstract: A method for treating a microbial infection involves administering an effective amount of a compound of the formula: wherein R1 is H, alkyl, aryl, heteroaryl, R2 is H, halogen, alkyl, aryl, heteroaryl, R3 is H, hydroxyl, alkoxy, alkyl, aryl, heteroaryl, amino, amino sulfonyl, acetamide, R4 is H, hydroxyl, alkoxy, alkyl, aryl, heteroaryl, amino, amino sulfonyl, acetamide, R5 is H, hydroxyl, alkoxy, alkyl, aryl, heteroaryl, amino, amino sulfonyl, acetamide, R6 is H, hydroxyl, alkoxy, alkyl, aryl, heteroaryl, amino, amino sulfonyl, acetamide, R7 is H, hydroxyl, alkoxy, alkyl, aryl, heteroaryl, amino, amino sulfonyl, acetamide, R8 is —CR3, O, S, wherein R5 and R6, R7 and R6, R5 and R4, R4 and R3 can cyclize forming a 3-10 member ring comprising C, O, S, and/or N optionally substituted with one or more R3; and administering light therapy, such as a photodynamic therapy (PDT) light source.

Abstract: Embodiments of the presently-disclosed subject matter include activators of HssRS that induce endogenous heme biosynthesis by perturbing central metabolism. These molecules are toxic to fermenting S. aureus, including clinically relevant small colony variants (SCVs). The utility of targeting fermenting bacteria is exemplified by the fact that this compound prevents the emergence of antibiotic resistance, enhances phagocyte killing, and reduces S. aureus pathogenesis. This small molecule is a powerful tool not only for studying bacterial heme biosynthesis and central metabolism, but also establishes targeting of fermentation as a viable antibacterial strategy.

Abstract: The present invention provides 2-pyrimidinyl pyrazolopyridine compounds, compositions containing the same, as well as processes for the preparation and their use as pharmaceutical agents.

Abstract: The present invention discloses pyrimidine derivatives, compositions and medicaments containing the same, as well as processes for the preparation and use of such compounds, compositions and medicaments. Such pyrimidine derivatives are useful in the treatment of diseases associated with inappropriate ErbB family kinase.