C07D311/18

Compositions and methods to treat diseases characterized by cellular proliferation and angiogenesis

Described herein are compositions and methods for preventing and/or treating diseases involving aberrant angiogenesis employing one or more benzo[c]chromen-6-one derivatives.

STABILIZATION OF AMYLOIDOGENIC IMMUNOGLOBULIN LIGHT CHAINS

In immunoglobulin light chain amyloidosis (AL), the unique antibody light chain (LC) protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. For treating AL patients, such as those with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, provided herein are small molecule compounds of Formula Ia, Formula Ib, and Formula II that are kinetic stabilizers of the native dimeric structure of full-length LCs, which compounds can slow or stop the amyloidogenicity cascade at its origin.

STABILIZATION OF AMYLOIDOGENIC IMMUNOGLOBULIN LIGHT CHAINS

In immunoglobulin light chain amyloidosis (AL), the unique antibody light chain (LC) protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. For treating AL patients, such as those with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, provided herein are small molecule compounds of Formula Ia, Formula Ib, and Formula II that are kinetic stabilizers of the native dimeric structure of full-length LCs, which compounds can slow or stop the amyloidogenicity cascade at its origin.

Thiol-based fluorescent probe for reactive species

Detection of nitroxyl (HNO), the transient one-electron reduced form of nitric oxide, is a significant challenge owing to its high reactivity with biological thiols (rate constants as high as 10.sup.9M.sup.−1 s.sup.−1). Reported herein is a new thiol-based HNO-responsive trigger that can compete against reactive thiols for HNO. This process forms an N-hydroxysulfenamide intermediate which cyclizes to release a masked fluorophore leading to fluorescence enhancement. To ensure a rapid cyclization step, the disclosed design capitalizes on two established physical organic phenomena: the alpha-effect and the Thorpe-Ingold effect. Using this new trigger, NitroxylFluor was developed; a selective HNO-responsive fluorescent probe. Treatment of NitroxylFluor with an HNO donor results in a 16-fold turn-on. This probe also exhibits excellent selectivity over various reactive nitrogen, oxygen, and sulfur species and efficacy in the presence of thiols (e.g., glutathione in mM concentrations). Also, live cell imaging of HNO using NitroxylFluor was performed.

SLC26A3 INHIBITORS AND USE THEREOF
20210363123 · 2021-11-25 ·

Provided herein are inhibitors of SLC26A3, which is an anion (CV, HCO.sub.3, oxalate) exchanger expressed in intestinal epithelial cells. SLC26A3 inhibitors have potential utility for treatment of constipation including chronic idiopathic constipation (CIC), opioid-induced constipation (OIC), constipation-predominant irritable bowel syndrome (IBS-C), cystic fibrosis-associated constipation, meconium ileus, distal intestinal obstruction syndrome, calcium oxalate kidney stone disease, enteric hyperoxaluria and primary hyperoxalurias.

SLC26A3 INHIBITORS AND USE THEREOF
20210363123 · 2021-11-25 ·

Provided herein are inhibitors of SLC26A3, which is an anion (CV, HCO.sub.3, oxalate) exchanger expressed in intestinal epithelial cells. SLC26A3 inhibitors have potential utility for treatment of constipation including chronic idiopathic constipation (CIC), opioid-induced constipation (OIC), constipation-predominant irritable bowel syndrome (IBS-C), cystic fibrosis-associated constipation, meconium ileus, distal intestinal obstruction syndrome, calcium oxalate kidney stone disease, enteric hyperoxaluria and primary hyperoxalurias.

SLC26A3 INHIBITORS AND USE THEREOF
20230339878 · 2023-10-26 ·

Provided herein are inhibitors of SLC26A3, which is an anion (Cl.sup.-, HCO.sub.3.sup.-, oxalate) exchanger expressed in intestinal epithelial cells. SLC26A3 inhibitors have potential utility for treatment of constipation including chronic idiopathic constipation (CIC), opioid-induced constipation (OIC), constipation-predominant irritable bowel syndrome (IBS-C), cystic fibrosis-associated constipation, meconium ileus, distal intestinal obstruction syndrome, calcium oxalate kidney stone disease, enteric hyperoxaluria and primary hyperoxalurias.

SLC26A3 INHIBITORS AND USE THEREOF
20230339878 · 2023-10-26 ·

Provided herein are inhibitors of SLC26A3, which is an anion (Cl.sup.-, HCO.sub.3.sup.-, oxalate) exchanger expressed in intestinal epithelial cells. SLC26A3 inhibitors have potential utility for treatment of constipation including chronic idiopathic constipation (CIC), opioid-induced constipation (OIC), constipation-predominant irritable bowel syndrome (IBS-C), cystic fibrosis-associated constipation, meconium ileus, distal intestinal obstruction syndrome, calcium oxalate kidney stone disease, enteric hyperoxaluria and primary hyperoxalurias.

PROCESS FOR PREPARING A COUMARIN-CAGED FORSKOLIN DERIVATIVE, FORSKOLIN DERIVATIVE AND USE OF SAID FORSKOLIN DERIVATIVE

A process for preparing coumarin-caged forskolin derivatives, the forskolin derivatives themselves and to uses of the same.

PROCESS FOR PREPARING A COUMARIN-CAGED FORSKOLIN DERIVATIVE, FORSKOLIN DERIVATIVE AND USE OF SAID FORSKOLIN DERIVATIVE

A process for preparing coumarin-caged forskolin derivatives, the forskolin derivatives themselves and to uses of the same.