Patent classifications
C07D498/22
Macrocyclic kinase inhibitor
Disclosed is a macrocyclic kinase inhibitor, wherein the compound, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof is as shown in formula I. Experiments show that the new compound as shown in formula I disclosed in the present invention exhibits an excellent TRK inhibitory activity, has a significant inhibitory effect on TRKA-mutant cell growth, and exhibits an excellent inhibitory effect on in vivo tumor growth, thus providing a new choice for the clinical treatment of diseases associated with abnormal TRK activity.
Macrocyclic indole derivatives
- Sarah Anna Liesa Johannes ,
- Philipp Buchgraber ,
- Ulrich Klar ,
- Clara Christ ,
- Kai Thede ,
- Joachim Kuhnke ,
- Manfred Moewes ,
- Knut Eis ,
- Amaury Ernesto Fernandez-Montalvan ,
- Nicolas Werbeck ,
- Ursula Mönning ,
- Philip Lienau ,
- Ulrike Sack ,
- Arne Scholz ,
- Michael H. Serrano-Wu ,
- Christopher Lemke ,
- David McKinney ,
- Mark Fitzgerald ,
- Christopher Nasveschuk ,
- Kiel Lazarski ,
- Steven James Ferrara ,
- Laura Furst ,
- Guo Wei ,
- Patrick Ryan McCarren
The present invention relates to macrocyclic indole derivatives of general formula (I) ##STR00001##
in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, A and L are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.
Macrocyclic indole derivatives
- Sarah Anna Liesa Johannes ,
- Philipp Buchgraber ,
- Ulrich Klar ,
- Clara Christ ,
- Kai Thede ,
- Joachim Kuhnke ,
- Manfred Moewes ,
- Knut Eis ,
- Amaury Ernesto Fernandez-Montalvan ,
- Nicolas Werbeck ,
- Ursula Mönning ,
- Philip Lienau ,
- Ulrike Sack ,
- Arne Scholz ,
- Michael H. Serrano-Wu ,
- Christopher Lemke ,
- David McKinney ,
- Mark Fitzgerald ,
- Christopher Nasveschuk ,
- Kiel Lazarski ,
- Steven James Ferrara ,
- Laura Furst ,
- Guo Wei ,
- Patrick Ryan McCarren
The present invention relates to macrocyclic indole derivatives of general formula (I) ##STR00001##
in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, A and L are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.
Near-infrared nerve-sparing fluorophores
The compounds provided herein are phenoxazines that can be used as far red to near-infrared nerve-sparing fluorescent compounds in medical procedures.
Near-infrared nerve-sparing fluorophores
The compounds provided herein are phenoxazines that can be used as far red to near-infrared nerve-sparing fluorescent compounds in medical procedures.
CYCLIC COMPOUNDS AND METHODS OF USING SAME
The present application relates to compounds of Formula (I), as defined herein, and pharmaceutically acceptable salts thereof. The present application also describes pharmaceutical composition comprising a compound of Formula (I), and pharmaceutically acceptable salts thereof, and methods of using the compounds and compositions for inhibiting kinase activity, and for treating cancer.
MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR
- Jeremy J. Clemens ,
- William Schulz Bechara ,
- Brett C. Bookser ,
- Thomas Cleveland ,
- Timothy R. Coon ,
- Michel Gallant ,
- Peter Grootenhuis ,
- Sara Sabina Hadida Ruah ,
- Julie Laterreur ,
- Mark Thomas MILLER ,
- Prasuna Paraselli ,
- Yeeman K. Ramtohul ,
- Thumkunta Jagadeeswar Reddy ,
- Claudio Sturino ,
- Lino Valdez ,
- Jinglan Zhou
This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), pharmaceutical compositions containing at least one such modulator, methods of treatment of cystic fibrosis using such modulators and pharmaceutical compositions, and processes for making such modulators.
MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR
- Jeremy J. Clemens ,
- William Schulz Bechara ,
- Brett C. Bookser ,
- Thomas Cleveland ,
- Timothy R. Coon ,
- Michel Gallant ,
- Peter Grootenhuis ,
- Sara Sabina Hadida Ruah ,
- Julie Laterreur ,
- Mark Thomas MILLER ,
- Prasuna Paraselli ,
- Yeeman K. Ramtohul ,
- Thumkunta Jagadeeswar Reddy ,
- Claudio Sturino ,
- Lino Valdez ,
- Jinglan Zhou
This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), pharmaceutical compositions containing at least one such modulator, methods of treatment of cystic fibrosis using such modulators and pharmaceutical compositions, and processes for making such modulators.
TRICYCLIC PI3K INHIBITOR COMPOUNDS AND METHODS OF USE
Tricyclic PI3k inhibitor compounds of Formula I with anti-cancer activity, anti-inflammatory activity, or immunoregulatory properties, and more specifically with PI3 kinase modulating or inhibitory activity are described. Methods are described for using the tricyclic PI3K inhibitor compounds of Formula I for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, organisms, or associated pathological conditions.
##STR00001##
Formula I compounds include stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof. The dashed lines indicate an optional double bond, and at least one dashed line is a double bond. The substituents are as described.
TRICYCLIC PI3K INHIBITOR COMPOUNDS AND METHODS OF USE
Tricyclic PI3k inhibitor compounds of Formula I with anti-cancer activity, anti-inflammatory activity, or immunoregulatory properties, and more specifically with PI3 kinase modulating or inhibitory activity are described. Methods are described for using the tricyclic PI3K inhibitor compounds of Formula I for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, organisms, or associated pathological conditions.
##STR00001##
Formula I compounds include stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof. The dashed lines indicate an optional double bond, and at least one dashed line is a double bond. The substituents are as described.