A61K31/497

N-(HETERO)ARYL, 2-(HETERO)ARYL-SUBSTITUTED ACETAMIDES FOR USE AS WNT SIGNALING MODULATORS
20180000832 · 2018-01-04 ·

The present invention relates to methods for modulating the Wnt signaling pathway using compounds of Formula (1),

##STR00001## wherein A.sup.1, Y and Z all represent rings.

N-(HETERO)ARYL, 2-(HETERO)ARYL-SUBSTITUTED ACETAMIDES FOR USE AS WNT SIGNALING MODULATORS
20180000832 · 2018-01-04 ·

The present invention relates to methods for modulating the Wnt signaling pathway using compounds of Formula (1),

##STR00001## wherein A.sup.1, Y and Z all represent rings.

BCR-ABL VARIANTS

A splice variant of bcr-abl mRNA that produces BCR-ABL protein with a truncated C-terminus and its role in resistance to treatment with kinase inhibitors is disclosed. Vectors for expressing the truncated gene product are provided as well as recombinant cells that express the truncated gene product from a cDNA construct. Also provided are methods compositions and kits for detecting the BCR-ABL splice variant. Additionally, methods for screening BCR-ABL kinase domain inhibitors which rely on the recombinant cells and methods of predicting likelihood for resistance of a CML patient with a BCR/ABL translocation respond to treatment with one or more BCR-ABL kinase inhibitors are also disclosed.

BCR-ABL VARIANTS

A splice variant of bcr-abl mRNA that produces BCR-ABL protein with a truncated C-terminus and its role in resistance to treatment with kinase inhibitors is disclosed. Vectors for expressing the truncated gene product are provided as well as recombinant cells that express the truncated gene product from a cDNA construct. Also provided are methods compositions and kits for detecting the BCR-ABL splice variant. Additionally, methods for screening BCR-ABL kinase domain inhibitors which rely on the recombinant cells and methods of predicting likelihood for resistance of a CML patient with a BCR/ABL translocation respond to treatment with one or more BCR-ABL kinase inhibitors are also disclosed.

BCR-ABL VARIANTS

A splice variant of bcr-abl mRNA that produces BCR-ABL protein with a truncated C-terminus and its role in resistance to treatment with kinase inhibitors is disclosed. Vectors for expressing the truncated gene product are provided as well as recombinant cells that express the truncated gene product from a cDNA construct. Also provided are methods compositions and kits for detecting the BCR-ABL splice variant. Additionally, methods for screening BCR-ABL kinase domain inhibitors which rely on the recombinant cells and methods of predicting likelihood for resistance of a CML patient with a BCR/ABL translocation respond to treatment with one or more BCR-ABL kinase inhibitors are also disclosed.

ISOINDOLINE OR ISOQUINOLINE COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Compounds of formula (I):

##STR00001##

wherein Het, R.sub.3, R.sub.4, R.sub.5, R.sub.7, R.sub.8, R.sub.9, T, p, p′, q, and q′ are as defined in the description.

Medicinal products containing the same which are useful in treating conditions requiring a pro-apoptotic agent.

ISOINDOLINE OR ISOQUINOLINE COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Compounds of formula (I):

##STR00001##

wherein Het, R.sub.3, R.sub.4, R.sub.5, R.sub.7, R.sub.8, R.sub.9, T, p, p′, q, and q′ are as defined in the description.

Medicinal products containing the same which are useful in treating conditions requiring a pro-apoptotic agent.

2-(PYRAZIN-2-YLCARBONYLAMINOMETHYL) BENZIMIDAZOLIUM COMPOUNDS AS EPITHELIAL SODIUM CHANNEL INHIBITORS
20180002314 · 2018-01-04 ·

The present invention relates to compounds of formula (I) or the tautomers or pharmacologically acceptable acid addition salts thereof, characterized by a topological polar surface area value (TPSA) of at least 145, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, X, and Z.sup.− have one of the meanings as defined in the specification, to the use of compounds of formula (I) as medicaments, to pharmaceutical compositions comprising at least one compound of formula (I), as well as to medicament combinations containing one or more compounds of formula (I). The compounds are ENaC inhibitors useful for the treatment of respiratory diseases and allergic diseases of the airways.

##STR00001##

2-(PYRAZIN-2-YLCARBONYLAMINOMETHYL) BENZIMIDAZOLIUM COMPOUNDS AS EPITHELIAL SODIUM CHANNEL INHIBITORS
20180002314 · 2018-01-04 ·

The present invention relates to compounds of formula (I) or the tautomers or pharmacologically acceptable acid addition salts thereof, characterized by a topological polar surface area value (TPSA) of at least 145, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, X, and Z.sup.− have one of the meanings as defined in the specification, to the use of compounds of formula (I) as medicaments, to pharmaceutical compositions comprising at least one compound of formula (I), as well as to medicament combinations containing one or more compounds of formula (I). The compounds are ENaC inhibitors useful for the treatment of respiratory diseases and allergic diseases of the airways.

##STR00001##

TETRA- AND PENTASUBSTITUTED BENZIMIDAZOLIUM COMPOUNDS USEFUL IN THE TREATMENT OF RESPIRATORY DISEASES
20180002312 · 2018-01-04 ·

The present invention relates to compounds of formula (I), or the tautomers or pharmacologically acceptable acid addition salts thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, X, and Z have one of the meanings as defined in the specification, to the use of compounds of formula (I) as a medicament, to pharmaceutical composition comprising at least one compound of formula (I), as well as to medicament combinations containing one or more compounds of formula (I).

##STR00001##