t0901317 and hexafluoroisopropanol

t0901317 has been researched along with hexafluoroisopropanol* in 2 studies

Other Studies

2 other study(ies) available for t0901317 and hexafluoroisopropanol

Article	Year
Identification of bicyclic hexafluoroisopropyl alcohol sulfonamides as retinoic acid receptor-related orphan receptor gamma (RORγ/RORc) inverse agonists. Employing structure-based drug design to improve pregnane X receptor (PXR) selectivity. Bioorganic & medicinal chemistry letters, 2018, 01-15, Volume: 28, Issue:2 We disclose the optimization of a high throughput screening hit to yield benzothiazine and tetrahydroquinoline sulfonamides as potent RORγt inverse agonists. However, a majority of these compounds showed potent activity against pregnane X receptor (PXR) and modest activity against liver X receptor α (LXRα). Structure-based drug design (SBDD) led to the identification of benzothiazine and tetrahydroquinoline sulfonamide analogs which completely dialed out LXRα activity and were less potent at PXR. Pharmacodynamic (PD) data for compound 35 in an IL-23 induced IL-17 mouse model is discussed along with the implications of a high Y Topics: Animals; Bridged Bicyclo Compounds; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug Design; Humans; Liver X Receptors; Male; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Structure; Pregnane X Receptor; Propanols; Receptors, Retinoic Acid; Receptors, Steroid; Retinoic Acid Receptor gamma; Structure-Activity Relationship; Sulfonamides	2018
Structure-based design of substituted hexafluoroisopropanol-arylsulfonamides as modulators of RORc. Bioorganic & medicinal chemistry letters, 2013, Dec-15, Volume: 23, Issue:24 The structure-activity relationships of T0901317 analogs were explored as RORc inverse agonists using the principles of property- and structure-based drug design. An X-ray co-crystal structure of T0901317 and RORc was obtained and provided molecular insight into why T0901317 functioned as an inverse agonist of RORc; whereas, the same ligand functioned as an agonist of FXR, LXR, and PXR. The structural data was also used to design inhibitors with improved RORc biochemical and cellular activities. The improved inhibitors possessed enhanced selectivity profiles (rationalized using the X-ray crystallographic data) against other nuclear receptors. Topics: Binding Sites; Crystallography, X-Ray; Drug Design; Drug Inverse Agonism; Humans; Hydrocarbons, Fluorinated; Interferon-gamma; Interleukin-17; Leukocytes, Mononuclear; Molecular Dynamics Simulation; Nuclear Receptor Subfamily 1, Group F, Member 3; Propanols; Protein Binding; Protein Structure, Tertiary; Structure-Activity Relationship; Sulfonamides	2013

Article

Year

Identification of bicyclic hexafluoroisopropyl alcohol sulfonamides as retinoic acid receptor-related orphan receptor gamma (RORγ/RORc) inverse agonists. Employing structure-based drug design to improve pregnane X receptor (PXR) selectivity.

Bioorganic & medicinal chemistry letters, 2018, 01-15, Volume: 28, Issue:2

We disclose the optimization of a high throughput screening hit to yield benzothiazine and tetrahydroquinoline sulfonamides as potent RORγt inverse agonists. However, a majority of these compounds showed potent activity against pregnane X receptor (PXR) and modest activity against liver X receptor α (LXRα). Structure-based drug design (SBDD) led to the identification of benzothiazine and tetrahydroquinoline sulfonamide analogs which completely dialed out LXRα activity and were less potent at PXR. Pharmacodynamic (PD) data for compound 35 in an IL-23 induced IL-17 mouse model is discussed along with the implications of a high Y

Topics: Animals; Bridged Bicyclo Compounds; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug Design; Humans; Liver X Receptors; Male; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Structure; Pregnane X Receptor; Propanols; Receptors, Retinoic Acid; Receptors, Steroid; Retinoic Acid Receptor gamma; Structure-Activity Relationship; Sulfonamides

2018

Structure-based design of substituted hexafluoroisopropanol-arylsulfonamides as modulators of RORc.

Bioorganic & medicinal chemistry letters, 2013, Dec-15, Volume: 23, Issue:24

The structure-activity relationships of T0901317 analogs were explored as RORc inverse agonists using the principles of property- and structure-based drug design. An X-ray co-crystal structure of T0901317 and RORc was obtained and provided molecular insight into why T0901317 functioned as an inverse agonist of RORc; whereas, the same ligand functioned as an agonist of FXR, LXR, and PXR. The structural data was also used to design inhibitors with improved RORc biochemical and cellular activities. The improved inhibitors possessed enhanced selectivity profiles (rationalized using the X-ray crystallographic data) against other nuclear receptors.

Topics: Binding Sites; Crystallography, X-Ray; Drug Design; Drug Inverse Agonism; Humans; Hydrocarbons, Fluorinated; Interferon-gamma; Interleukin-17; Leukocytes, Mononuclear; Molecular Dynamics Simulation; Nuclear Receptor Subfamily 1, Group F, Member 3; Propanols; Protein Binding; Protein Structure, Tertiary; Structure-Activity Relationship; Sulfonamides

2013