Provided are 1,4-diphenyl-1H-imidazole and 2,4-diphenylthiazole derivatives having a structure represented by Formula I, a preparation method therefor and uses thereof: ##STR00001##
wherein R.sub.1 is any one of H, OH, and OCH.sub.3, R.sub.2 is any one of H, NO.sub.2, CH.sub.3, CF.sub.3, SO.sub.2CH.sub.3, COOCH.sub.3, or CONHCH.sub.3, R.sub.3 is any one of H, NO.sub.2, OCH.sub.3, or CF.sub.3, R.sub.4 is selected from H, CF.sub.3, or Cl, R.sub.5 is any one of H, Cl, CF.sub.3, or NHCH.sub.3, and R.sub.6 is any one of OCF.sub.3, CF.sub.3, or CN; V is either C or N, W is either CH or N, X is a C atom, Y is either CH or N, and Z is either CH or S. This compound can be used in preparation of anti-inflammatory adjuvants, TLR1 or TLR2 agonists, and anti-tumor agents and for regulating the activity activation level of TLR1 and TLR2 alkaline phosphatases in vitro and in vivo.

Provided are 1,4-diphenyl-1H-imidazole and 2,4-diphenylthiazole derivatives having a structure represented by Formula I, a preparation method therefor and uses thereof: ##STR00001##
wherein R.sub.1 is any one of H, OH, and OCH.sub.3, R.sub.2 is any one of H, NO.sub.2, CH.sub.3, CF.sub.3, SO.sub.2CH.sub.3, COOCH.sub.3, or CONHCH.sub.3, R.sub.3 is any one of H, NO.sub.2, OCH.sub.3, or CF.sub.3, R.sub.4 is selected from H, CF.sub.3, or Cl, R.sub.5 is any one of H, Cl, CF.sub.3, or NHCH.sub.3, and R.sub.6 is any one of OCF.sub.3, CF.sub.3, or CN; V is either C or N, W is either CH or N, X is a C atom, Y is either CH or N, and Z is either CH or S. This compound can be used in preparation of anti-inflammatory adjuvants, TLR1 or TLR2 agonists, and anti-tumor agents and for regulating the activity activation level of TLR1 and TLR2 alkaline phosphatases in vitro and in vivo.

A compound for use in the treatment of a disease ameliorated by the inhibition of Notum of formula (I): (I) ##STR00001##

A compound for use in the treatment of a disease ameliorated by the inhibition of Notum of formula (I): (I) ##STR00001##

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof:
X-A-Y-L-R  (I)
which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

The present invention is concerned with novel deuterated Angiotensin-Converting Enzyme-2 (ACE-2) inhibitors of general structural formula I, their optically active enantiomers and diastereoisomers, and pharmaceutical salts and compositions thereof, as well as combination therapies which include compounds of the present invention, ##STR00001## These compounds have high potency and selectivity for Angiotensin-Converting Enzyme-2 (ACE-2) inhibition, and are useful in the treatment of infectious respiratory diseases including the pandemic disease Covid-19, Severe Acute Respiratory Syndrome (SARS-CoV-2), Severe Acute Respiratory Syndrome (SARS-CoV), and other diseases caused by coronaviruses.

The present invention is concerned with novel deuterated Angiotensin-Converting Enzyme-2 (ACE-2) inhibitors of general structural formula I, their optically active enantiomers and diastereoisomers, and pharmaceutical salts and compositions thereof, as well as combination therapies which include compounds of the present invention, ##STR00001## These compounds have high potency and selectivity for Angiotensin-Converting Enzyme-2 (ACE-2) inhibition, and are useful in the treatment of infectious respiratory diseases including the pandemic disease Covid-19, Severe Acute Respiratory Syndrome (SARS-CoV-2), Severe Acute Respiratory Syndrome (SARS-CoV), and other diseases caused by coronaviruses.

Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein:

##STR00001##

wherein m, n, p, R′, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.8, Z, W, Y, and Z are as defined herein.

Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein:

##STR00001##

wherein m, n, p, R′, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.8, Z, W, Y, and Z are as defined herein.

The present invention relates to novel crystalline Forms C, C′, D′ and H3 of 5-({[2-amino (4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid and methods of preparing the same.