This invention provides a compound having the structure

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wherein α, β, X, Y, and R.sub.1-R.sub.11 are defined herein. This invention also provides a pharmaceutical composition comprising the above compounds, a method of inhibiting the activity and/or levels of a matrix metalloproteinase (MMP), a method of inhibiting the production of a cytokine in a population of cells, a method of inhibiting the production of a growth factor in a population of cells, and a method of inhibiting NF.sub.K-B activation in a population of cells.

Small molecule calpain modulator compositions and pharmaceutical compositions can be prepared and used as therapeutic agents. Exemplary compositions include non-macrocyclic a-keto amide derivatives. The therarapeutic agents can be used for treating fibrotic disease or a resulting secondary disease state or condition. The small molecules can competitively bind with calpastatin and/or inhibit calpain through contact with CAPN1, CAPN2, and/or CAPN9 enzymes.

The present invention relates to compounds of formula (Ia) and the use thereof as inhibitors of P. aeruginosa virulence factor LasB. Formula (Ia). These compounds are useful in the treatment of bacterial infections, especially caused by P. aeruginosa.

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Disclosed are a reduction method and reduction product of an alkenyl active methylene compound. The reduction reaction comprises the following steps: taking an alkenyl active methylene compound as a substrate, a metal hydride as a reducing agent, and a palladium compound as a catalyst, performing a reduction reaction to obtain a reduction product, and then reducing the alkenyl active methylene compound. The reduction system is a simple method for reducing the alkenyl active methylene compound, and the used hydride and palladium compound catalyst are both reagents that could easily be obtained in a laboratory. Compared with conventional hydrogen hydrogenation methods and reduction methods of reducing agents, the method is easier to operate, higher in safety, mild in conditions, and high in reaction yield, a reaction in a one-pot two-step manner can be achieved, and high atom economy and step economy can be obtained.

Disclosed are a reduction method and reduction product of an alkenyl active methylene compound. The reduction reaction comprises the following steps: taking an alkenyl active methylene compound as a substrate, a metal hydride as a reducing agent, and a palladium compound as a catalyst, performing a reduction reaction to obtain a reduction product, and then reducing the alkenyl active methylene compound. The reduction system is a simple method for reducing the alkenyl active methylene compound, and the used hydride and palladium compound catalyst are both reagents that could easily be obtained in a laboratory. Compared with conventional hydrogen hydrogenation methods and reduction methods of reducing agents, the method is easier to operate, higher in safety, mild in conditions, and high in reaction yield, a reaction in a one-pot two-step manner can be achieved, and high atom economy and step economy can be obtained.

The present invention provides processes for the preparation of ivacaftor using novel intermediates and a process for its preparation.

The present invention provides processes for the preparation of ivacaftor using novel intermediates and a process for its preparation.

Methods of treating or suppressing mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS), Kearns-Sayre Syndrome (KSS), are disclosed, as well as compounds useful in the methods of the invention, such as 4-(p-quinolyl)-2-hydroxybutanamide derivatives. Methods and compounds useful in treating other disorders such as amyotrophic lateral sclerosis (ALS), Huntington's disease, Parkinson's disease, and pervasive developmental disorders such as autism are also disclosed. Energy biomarkers useful in assessing the metabolic state of a subject and the efficacy of treatment are also disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods, are also disclosed.

Methods of treating or suppressing mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS), Kearns-Sayre Syndrome (KSS), are disclosed, as well as compounds useful in the methods of the invention, such as 4-(p-quinolyl)-2-hydroxybutanamide derivatives. Methods and compounds useful in treating other disorders such as amyotrophic lateral sclerosis (ALS), Huntington's disease, Parkinson's disease, and pervasive developmental disorders such as autism are also disclosed. Energy biomarkers useful in assessing the metabolic state of a subject and the efficacy of treatment are also disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods, are also disclosed.

Methods of treating or suppressing mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS), Kearns-Sayre Syndrome (KSS), are disclosed, as well as compounds useful in the methods of the invention, such as 4-(p-quinolyl)-2-hydroxybutanamide derivatives. Methods and compounds useful in treating other disorders such as amyotrophic lateral sclerosis (ALS), Huntington's disease, Parkinson's disease, and pervasive developmental disorders such as autism are also disclosed. Energy biomarkers useful in assessing the metabolic state of a subject and the efficacy of treatment are also disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods, are also disclosed.