Abstract: The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

Abstract: The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

Abstract: Compounds having a structure according to formula (I) where RA, RB, RC, RD, RE, and RF are as defined herein, are useful as prokinetic agents.

Abstract: Compounds having the structure of formula I wherein R1, R2, R3, R4, R5, and R6 are as defined herein, are prokinetic agents and can be used to treat disorders of gastric motility.

Abstract: 9-Desoxoerythromycin compounds of formula I wherein R1, R2, R3, R4, and R5 are as defined herein, are useful as prokinetic agents for treating disorders of gastric motility.

Abstract: Compounds having a structure according to formula (I) where RA, RB, RC, RD, RE, and RF are as defined herein, are useful as prokinetic agents.

Abstract: 9-Desoxoerythromycin compounds of formula I wherein R1, R2, R3, R4, and R5 are as defined herein, are useful as prokinetic agents for treating disorders of gastric motility.

Abstract: Motilide compounds having the formula (I), wherein R1, R2, R3, and R4 are as defined herein, and methods for their preparation and use in the treatment of diseases or conditions characterized by impaired gastric motility.

Abstract: Compounds having the structure of formula I wherein R1, R2, R3, R4, R5, and R6 are as defined herein, are prokinetic agents and can be used to treat disorders of gastric motility.

Abstract: Compounds of formula (I) wherein A is and R1, R2, R3, and R4 are as defined herein, are prokinetic agents and can be used to treat disorders of gastric motility.

Abstract: The present invention relates to in vitro methods for evaluating compounds that better correlate with therapeutic efficiency than evaluating compounds based on potency alone. In general, the inventive method comprises: (i) determining a potency value for a compound against its target receptor; (ii) determining a desensitization value for the compound against its target receptor; and (iii) comparing the potency value with the desensitization value. If the desired action of a compound is as a receptor agonist, then the compound's desensitization value should be larger than the compound's potency value. This ensures that the concentration of a compound required for potency will not also cause the receptor to desensitize at the same time, thus in an essence nullifying the desired effect. The inventive methods are used to evaluate novel motilide compounds as well as ABT-229 and EM-574, two motilide compounds for which clinical trials have been initiated.

Abstract: Motilide compounds having the formula (I), 1

Abstract: The present invention provides novel macrolide compounds of the formulas wherein: R is hydroxyl or methoxy; R1 is selected from the group consisting of hydrogen, hydroxyl, halide, NH2, OR9, where R9 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, aryl or heteroaryl and R10 and R11 are each independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, or aryl; R2 and R3 are each independently selected from the group consisting of hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, aryl, alkylaryl, alkenylaryl alkynylaryl or R2 and R3 together form a cycloalkyl or a cycloaryl moiety; R4 is hydrogen or methyl; R5 is hydrogen, hydroxyl, oxo, or together with R6 and the carbons to which they are attached form a cyclic carbonate; R6 is hydrogen, hydroxyl, OR12 where R12 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, or together with R5 and the carbons to which they are attached form a cyclic carbonate; R7 is methyl, C3-C10 alkyl, C2-C10 alkenyl, C2-C10 alkyn

Abstract: The present invention provides novel macrolide compounds of the formulas 1

Abstract: The present invention provides novel macrolide compounds of the formulas wherein: R is hydroxyl or methoxy; R1 is selected from the group consisting of hydrogen, hydroxyl, halide, NH2, OR9,  where R9 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, aryl or heteroaryl and R10 and R11 are each independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, or aryl; R2 and R3 are each independently selected from the group consisting of hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, aryl, alkylaryl, alkenylaryl, alkynylaryl or R2 and R3 together form a cycloalkyl or a cycloaryl moiety; R4 is hydrogen or methyl; R5 is hydrogen, hydroxyl, oxo, or together with R6 and the carbons to which they are attached form a cyclic carbonate; R6 is hydrogen, hydroxyl, OR12 where R12 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, or together with R5 and the carbons to which they are attached form a cyclic carbonate; R7 is methyl, C3-C10 alkyl, C2-C10 alkenyl, C2-C1

Abstract: The present invention relates to in vitro methods for evaluating compounds that better correlate with therapeutic efficiency than evaluating compounds based on potency alone. In general, the inventive method comprises: (i) determining a potency value for a compound against its target receptor; (ii) determining a desensitization value for the compound against its target receptor; and (iii) comparing the potency value with the desensitization value. If the desired action of a compound is as a receptor agonist, then the compound's desensitization value should be larger than the compound's potency value. This ensures that the concentration of a compound required for potency will not also cause the receptor to desensitize at the same time, thus in an essence nullifying the desired effect. The inventive methods are used to evaluate novel motilide compounds as well as ABT-229 and EM-574, two motilide compounds for which clinical trials have been initiated.

Abstract: The present invention provides novel macrolide compounds of the formulas 1