Thiazolidine carboxamide derivatives as modulators of the prostaglandin f receptor

Abstract

The present invention is related to thiazolidine carboxamide derivatives of formula (II) for the treatment and / or prophylaxis of preterm labor, premature birth, dysmenorrhea and for stopping labor prior to cesarean delivery. G is selected from the group consisting of C1-C6-alkyl aryl, C1-C6-alkyl heteroaryl, C1-C6 Alkyl cycloalkyl, C1-C6-alkyl heteroaryl, aryl, heteroaryl, C3-C8-cycloalkyl or -heterocycloalkyl, said cycloalkyl or aryl or hetetoaryl groups may be fused with cycloalkyl or aryl or heteroaryl groups. R1 is selected from the group consisting of aryl, heteroaryl, C3-C8-cycloalkyl or -heterocyclo-alkyl, said (hetero)cycloalkyl or aryl or heteroaryl groups may be fused with (hetero)cycloalkyl or aryl or heteroaryl groups. R2 is selected from the group consisting of H, carboxy, acyl, alkoxycarbonyl, aminocarbonyl, C1-C5-alkyl carboxy, C1-C5-alkyl acyl, C1-C5-alkyl alkoxycarbonyl, C1-C5-alkyl aminocarbonyl, C1-C5-alkyl acyloxy, C1-C5-alkyl acylamino, C1-C5-alkyl ureido, C1-C5alkyl amino, C1-C5-alkyl alkoxy, C1-C5-alkyl sulfanyl, C1-C5-alkyl sulfinyl, C1-C5-alkyl sulfonyl, C1-C5-alkyl sulfonylamino, C1-C5-alkyl sulfonyloxy, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, aryl, heteroaryl, C3-C8-cycloalkyl, heterocycloalkyl, C1-C6-alkyl aryl, C2-C6-alkyl heteroaryl, C1-C6-alkyl cycloalkyl, C1-C6-alkyl heterocycloalkyl, C2-C6-alkenyl aryl, C2-C6-alkenyl heteroaryl, C2-C6-alkynyl aryl, or C2-C6-alkynyl heteroaryl.

Description

FIELD OF THE INVENTION [0001] This present invention is related to thiazolidine carboxamide derivatives of formula (II) for the treatment and / or prophylaxis of preterm labor, premature birth, dysmenorrhea and for stopping labor prior to cesarean delivery. Specifically, the present invention is related to substituted thiazolidine carboxamide derivatives for the modulation, notably the inhibition of the activity or function of the prostaglandin receptors, particularly of the prostaglandin F2α receptor. Also, the present invention is related to novel thiazolidine carboxamide derivatives of formulae (I) and (Ia). BACKGROUND OF THE INVENTION [0002] In the field of obstetrics, one of the most important problems is the management of preterm labor and premature birth as they represent a major cause of perinatal morbidity and mortality. [0003] In recent years, strong evidence has accumulated indicating that the hormone oxytocin plays a major role in initiating labor in mammals, notably in hu...

AI Technical Summary

Problems solved by technology

In the field of obstetrics, one of the most important problems is the management of preterm labor and premature birth as they represent a major cause of perinatal morbidity and mortality.

For the treatment of preterm labor, several approaches have been considered such as the use of magnesium sulfate, ethanol or therapeutic agents acting as β2 adrenergic agonists or oxytocin antagonists: With the use of magnesium sulfate, it has been observed that plasma concentrations above the therapeutic range of 4 to 8 mg / dL can cause inhibition of cardiac conduction and neuromuscular transmission, respiratory depression and cardiac arrest, thus making this agent unsuitable notably when the renal function is impaired.

Ethanol is effective in preventing premature labor, but it does not produce a corresponding reduction in the incidence of fetal respiratory distress.

Also, ethanol is assumed to have a negative impact on the fetus.

Therefore, there is strong evidence that interfering with the prostaglandin pathway by blocking selectively the contractile FP receptor will delay the progression of labor.

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