Non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including obesity, diabetes, inflammatory and immune diseases, and have the structure of formula (I) or an enantiomer, a diastereomer, a pharmaceutically acceptable salt, or hydrate thereof, where J is selected from NR1 or C(R4)(R4a); K is selected from NR2 or C(R5)(R5a); L is selected from NR3 or C(R6)(R6a); and A, X, Y, R1, R2, R3, R4, R4a, R5, R5a, R6, R6a, R8, R10, R11, and n are defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.

MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-kB ACTIVITY AND USE THEREOF

A class of novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including obesity, diabetes, inflammatory and immune diseases, and have the structure of formula (I) its stereoisomers thereof, or a solvate thereof, or a pharmaceutically acceptable salt thereof, where Z is S, O or NH; and R, R1, R2 Ra, Rb, Rc, Rd, Z, A and B are defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.

Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof

PROBLEM TO BE SOLVED: To provide a cover for an underground structure capable of stably holding a floatation locking state of a cover body, by surely preventing disconnection of engagement between a floatation lock member and a locking part of a receiving frame more than usual, when locked on the receiving frame in a state of floating the cover body by a constant height from the receiving frame, when uplift pressure is generated in the underground structure, by restraining the floatation lock member from abrading by vibration such as vehicle traffic time.SOLUTION: A circular arc-shaped part 63 having an external shape of a substantially circular arc shape is provided in a floatation lock member 60, and this circular arc-shaped part 63 is slidably held in the direction for copying after the external shape of the circular arc-shaped part 63 by a holding part 71 provided on an undersurface of a cover body 20. When the cover body 20 floats, one tip side locking claw part 61 of the floatation lock member 60 engages with a locking part 12 of a receiving frame 10, and an abutting part 62 on the other tip side of the floatation lock member 60 abuts on an abutting receiving part 72, so that a floatation locking state of the cover body 20 is stably held.SELECTED DRAWING: Figure 9

Cover for underground structure

NEW MATERIAL:A 5-substituted indazole derivative of formula I: [R is H, CH3, or OCH3; X is O or two groups R2 and R3 (R is H or CH3; R is OH, CH , or OCH3 group)]. EXAMPLE:4,5,6,7-Tetrahydro-1-phenylindazole-5-carboxylic methyl ester. USE:Safe medicines having improved anti-inflammatory, analgesic, and antipyretic actions with slight toxicity and side effects. PROCESS:A compound of formula II is esterified with diazomethane to give the objective compound of formula I wherein R is OCH3 and X is O. The ester group is selectively reduced to form the desired compound of formula I wherein R and R are hydrogens and R is OH group. The compound thus obtained in then oxidized, methylated, oxidized, and methylated twice to give the objective compound of formula I wherein R and X are different.

Oomori Hitoshi

Papers

55substituted indazole derivative