Disclosed herein, inter alia, are inhibitors of alpha 2 beta 1 integrin and methods of using the same.

Disclosed herein, inter alia, are inhibitors of alpha 2 beta 1 integrin and methods of using the same.

The invention relates to compounds of Formula (I)

##STR00001##

wherein X.sup.1, X.sup.2, X.sup.3, Y, R.sup.1, R.sup.2A, R.sup.2B, R.sup.3, and R.sup.4 are as described in the description; to their preparation, to pharmaceutically acceptable salts thereof, to pharmaceutical compositions containing one or more compounds of Formula (I), and to the use of such compounds as medicaments, especially as Kv7 openers.

The invention relates to compounds of Formula (I)

##STR00001##

wherein X.sup.1, X.sup.2, X.sup.3, Y, R.sup.1, R.sup.2A, R.sup.2B, R.sup.3, and R.sup.4 are as described in the description; to their preparation, to pharmaceutically acceptable salts thereof, to pharmaceutical compositions containing one or more compounds of Formula (I), and to the use of such compounds as medicaments, especially as Kv7 openers.

The present disclosure provides processes and apparatuses for the scaled-up manufacture of lomustine via continuous flow manufacture. Such continuous flow processes may optionally include the crystallization of lomustine and the apparatuses may optionally include crystallization apparatuses/reactors in either batch or continuous flow design. In one aspect of the disclosure, a process for making lomustine is provided comprising treating solutions of 2-chloroethylisocyanate with a solution of cyclohexylamine with continuous-flow pumps in a gram-flow reactor to form a combined solution, adding deionized water with a continuous flow-pump to the combined solution to form a liquid-organic phase solution, extracting the organic phase from the solution and treating with a solution of t-butyl nitrite with a continuous flow pump in a gram flow reactor to form lomustine.

The present disclosure provides processes and apparatuses for the scaled-up manufacture of lomustine via continuous flow manufacture. Such continuous flow processes may optionally include the crystallization of lomustine and the apparatuses may optionally include crystallization apparatuses/reactors in either batch or continuous flow design. In one aspect of the disclosure, a process for making lomustine is provided comprising treating solutions of 2-chloroethylisocyanate with a solution of cyclohexylamine with continuous-flow pumps in a gram-flow reactor to form a combined solution, adding deionized water with a continuous flow-pump to the combined solution to form a liquid-organic phase solution, extracting the organic phase from the solution and treating with a solution of t-butyl nitrite with a continuous flow pump in a gram flow reactor to form lomustine.

Disclosed are 1,3-Dioxoindene derivatives, pharmaceutically acceptable salts thereof or enantiomers, a preparation method thereof, and a pharmaceutical composition for the prevention or treatment of viral diseases, comprising the same as an active ingredient. The 1,3-Dioxoindene derivatives have excellent inhibitory activity against picornaviruses including coxsackie-, entero-, echo-, Polio-, and rhinoviruses, as well as exhibiting low cytotoxicity, so that they can be useful as an active ingredient of a pharmaceutical composition for the prevention or treatment of viral diseases including poliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viral meningitis, hand-foot-and-mouth disease, vesicular disease, hepatitis A, myositis, myocarditis, pancreatitis, diabetes, epidemic myalgia, encephalitis, cold, herpangina, foot-and-mouth disease, asthma, chronic obstructive pulmonary disease, pneumonia, sinusitis or otitis media.

Disclosed are 1,3-Dioxoindene derivatives, pharmaceutically acceptable salts thereof or enantiomers, a preparation method thereof, and a pharmaceutical composition for the prevention or treatment of viral diseases, comprising the same as an active ingredient. The 1,3-Dioxoindene derivatives have excellent inhibitory activity against picornaviruses including coxsackie-, entero-, echo-, Polio-, and rhinoviruses, as well as exhibiting low cytotoxicity, so that they can be useful as an active ingredient of a pharmaceutical composition for the prevention or treatment of viral diseases including poliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viral meningitis, hand-foot-and-mouth disease, vesicular disease, hepatitis A, myositis, myocarditis, pancreatitis, diabetes, epidemic myalgia, encephalitis, cold, herpangina, foot-and-mouth disease, asthma, chronic obstructive pulmonary disease, pneumonia, sinusitis or otitis media.

The present invention includes compounds useful in preventing or treating cancer in a subject in need thereof. The present invention also includes methods of preventing or treating cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.

The present invention includes compounds useful in preventing or treating cancer in a subject in need thereof. The present invention also includes methods of preventing or treating cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.