C07D311/08

DUAL NAV1.2/5HT2a INHIBITORS FOR TREATING CNS DISORDERS

Compounds of formula I:

##STR00001##

are disclosed, as are pharmaceutical compositions containing such compounds. Methods of treating neurological or psychiatric disorders in a patient in need are also disclosed. Such disorders include depression, bipolar disorder, pain, schizophrenia, obsessive compulsive disorder, addiction, social disorder, attention deficit hyperactivity disorder, an anxiety disorder, autism, a cognitive impairment, or a neuropsychiatric symptom such as apathy, depression, anxiety, psychosis, aggression, agitation, impulse control disorders, and sleep disorders in neurological disorders such as Alzheimer's and Parkinson's diseases.

SELF-IMMOLATIVE PROBES FOR ENZYME ACTIVITY DETECTION

Provided is a compound having the structure:


(SIG)-(SI-MOD).sub.m

where SIG is a signaling molecule, SI is a self-immolative structure bound to SIG such that SIG has a reduced signal relative to the signal of SIG without SI, MOD is a moiety bound to SI that is subject to modification by an activator, and m is an integer from 1 to about 10. When MOD is modified by an activator, SI is destabilized and self-cleaved from SIG such that SIG generates an increased signal. Also provided are methods of determining whether a sample, such as a cell, comprises an activator, such as a nitroreducase, using the compound. Further provided are methods of determining whether a mammalian cell is hypoxic using the compound where nitroreductase is the activator. A method of detecting a microorganism that comprises a nitroreductase using the compound where nitroreductase is the activator is also provided.

SELF-IMMOLATIVE PROBES FOR ENZYME ACTIVITY DETECTION

Provided is a compound having the structure:


(SIG)-(SI-MOD).sub.m

where SIG is a signaling molecule, SI is a self-immolative structure bound to SIG such that SIG has a reduced signal relative to the signal of SIG without SI, MOD is a moiety bound to SI that is subject to modification by an activator, and m is an integer from 1 to about 10. When MOD is modified by an activator, SI is destabilized and self-cleaved from SIG such that SIG generates an increased signal. Also provided are methods of determining whether a sample, such as a cell, comprises an activator, such as a nitroreducase, using the compound. Further provided are methods of determining whether a mammalian cell is hypoxic using the compound where nitroreductase is the activator. A method of detecting a microorganism that comprises a nitroreductase using the compound where nitroreductase is the activator is also provided.

Compounds and methods for assaying activity of lysosomal storage diseases

A compound having the formula: ##STR00001##
wherein each R.sup.1 is independently H or D; R.sup.2 is alkyl or cycloalkyl; R.sup.3 is a H, alkyl, cycloalkyl, heterocycloalkyl, or carboxylate; E is NR.sup.4 or O; R.sup.4 is H or alkyl; n is an integer from 1 to 20; and C* represents a natural distribution of .sup.12C and .sup.13C, or enrichment with .sup.13C.

C7-FLUORO SUBSTITUTED TETRACYCLINE COMPOUNDS

The present invention is directed to a compound represented by Structural Formula (A):

##STR00001##

or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.

C7-FLUORO SUBSTITUTED TETRACYCLINE COMPOUNDS

The present invention is directed to a compound represented by Structural Formula (A):

##STR00001##

or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.

Coumarin dyes and conjugates thereof

The present invention describes novel 7-alkylamino-3-(thienyl) coumarin fluorescent dyes of formula (I) ##STR00001## These dyes are water soluble, can be excited by the 405 nm excitation source and exhibit a large Stokes shift (80 nm). Furthermore, the dyes possess a reactive group for the labeling of biomolecules or other analytes.

Small Molecule Agonists and Antagonists of NR2F6 Activity in Humans
20180214413 · 2018-08-02 ·

The present technology is directed to modulators of nuclear receptor activity, specifically to the modulation of NR2F6 activity and NR2F6 utilizing compounds, and the immune modulation and modulation of cancer stem cell activity through administration of compounds described herein to humans.

BIPHENYL AMIDES WITH MODIFIED ETHER GROUPS AS HSP90 INHIBITORS AND HSP70 INDUCERS
20180057446 · 2018-03-01 ·

Provided herein are compounds of the formulas: (I) wherein: n, X.sub.2, R.sub.3, R.sub.3, R.sub.4, R.sub.4, R.sub.5, R.sub.5, R.sub.6, and R.sub.6 are as defined herein. Pharmaceutical compositions of the compounds are also provided. In some aspects, these compounds may be used for the treatment of diseases, including diabetic peripheral neuropathy or cancer.

##STR00001##

Compounds useful as immunomodulators

Disclosed are compounds of Formula (I): (I). Also disclosed are methods of using such compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of virological diseases or disorders and cancer. ##STR00001##