The present disclosure provides a benzene fused heterocyclic derivative of Formula (I): is a single or double bond; n is an integer of 0 or 1; A is —CH.sub.2—, —CH(OH)—, or —C(O)—; G is C or N; X is —CH.sub.2—, O, or —C(O)—; Y is alkyl, aryl, or heterocyclic alkyl optionally substituted with at least one substituent independently selected from a group consisting of: H, halogen, alkyl, alkyl substituted with at least one halogen, aryl, aryl substituted with at least one halogen, —NR.sub.y1R.sub.y2, —OR.sub.y1, —R.sub.y1C(O)R.sub.y3, —C(O)R.sub.y1, —C(O)OR.sub.y2, —C(O)OR.sub.y2Ry3, —NR.sub.y1C(O)R.sub.y2, —NR.sub.y1C(O)NR.sub.y2R.sub.y3, —NR.sub.y1C(O)OR.sub.y2R.sub.y3, —NR.sub.y1C(O)R.sub.y2OR.sub.y3, C(O)NR.sub.y1(R.sub.y2R.sub.y3), —C(O)NR.sub.y1(R.sub.y2OR.sub.y1), —OR.sub.y2R.sub.y3, and —OR.sub.y2OR.sub.y3, wherein each of R.sub.y1 and R.sub.y2 is independently selected from a group consisting of H, oxygen, alkyl, and aryl, and R.sub.y3 is aryl optionally substituted with at least one halogen; Z is —NR.sub.z1R.sub.z2, —NR.sub.z1R.sub.z3, —OR.sub.z1, —OR.sub.z1R.sub.z3, —C(O)R.sub.z1R.sub.z3, —C(O)OR.sub.z1R.sub.z3, —NR.sub.z1C(O)R.sub.z2R.sub.z3, —NR.sub.z1C(O)OR.sub.z2R.sub.z3, —C(O)NR.sub.z1R.sub.z3, or OR.sub.z2OR.sub.z3, wherein each of R.sub.z1 and R.sub.z2 is independently selected from a group consisting of H, oxygen, alkyl and aryl, and R.sub.z3 is aryl optionally substituted with at least one substituent independently selected from a group consisting of halogen, OH, —R.sub.zaCOOR.sub.zb, —OR.sub.zaCOOR.sub.zb, —R.sub.zaSO.sub.2R.sub.zb, —R.sub.zaSO.sub.2NR.sub.zbR.sub.zcR.sub.zd, —R.sub.zaC(O)R.sub.zbR.sub.zc, —R.sub.zaC(O)NR.sub.zbR.sub.zcR.sub.zd, —RZ.sub.aC(O)NR.sub.zbSO.sub.2R.sub.zc, wherein Rza is nil or alkyl, R.sub.zb is H or alkyl, each of R.sub.zb and R.sub.zc is independently selected from a group consisting of H, OH, alkyl, aryl, alkoxyl, or NR.sub.zbR.sub.zc is a nitrogen-containing heterocyclic alkyl ring, R.sub.zd is nil or a sulfonyl alkyl group. ##STR00001##

Provided herein are compounds of Formulae (RL), (I), (II), (III), (IV), and (V), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, prodrugs, and isotopically labeled derivatives thereof. Also provided are pharmaceutical compositions, kits, and methods involving the inventive compounds for the treatment of metabolic disorders (e.g., diabetes, hyperglycemia, impaired glucose tolerance, insulin resistance, obesity). The compound are useful as substrate selective inhibitors of insulin-degrading enzyme (IDE). ##STR00001##

Provided herein are compounds of Formulae (RL), (I), (II), (III), (IV), and (V), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, prodrugs, and isotopically labeled derivatives thereof. Also provided are pharmaceutical compositions, kits, and methods involving the inventive compounds for the treatment of metabolic disorders (e.g., diabetes, hyperglycemia, impaired glucose tolerance, insulin resistance, obesity). The compound are useful as substrate selective inhibitors of insulin-degrading enzyme (IDE). ##STR00001##

A compound of formula (I) or a pharmaceutically acceptable salt thereof. The compound is useful in therapy, e.g. for the treatment of a condition or disorder associated with nicotinamide adenine dinucleotide phosphate oxidase 4 or 2 (Nox4 or Nox2) activity. A pharmaceutical composition comprising the compound.

A compound of formula (I) or a pharmaceutically acceptable salt thereof. The compound is useful in therapy, e.g. for the treatment of a condition or disorder associated with nicotinamide adenine dinucleotide phosphate oxidase 4 or 2 (Nox4 or Nox2) activity. A pharmaceutical composition comprising the compound.

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

In an embodiment of the invention, a composition for treating a cell population comprises a medicant. The medicant moiety can be an illudofulvene analog. In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The affinity moiety can be an antibody, an antibody fragment, a receptor protein, a peptidic growth factor, an anti-angiogenic protein, a specific binding peptide, protease cleavable peptide, a glycopeptide, a peptide, a peptidic toxin, a protein toxin and an oligonucleotide. The affinity moiety can be covalently bound to the medicant via a linker.

In an embodiment of the invention, a composition for treating a cell population comprises a medicant. The medicant moiety can be an illudofulvene analog. In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The affinity moiety can be an antibody, an antibody fragment, a receptor protein, a peptidic growth factor, an anti-angiogenic protein, a specific binding peptide, protease cleavable peptide, a glycopeptide, a peptide, a peptidic toxin, a protein toxin and an oligonucleotide. The affinity moiety can be covalently bound to the medicant via a linker.

A compound of formula (Ie):

##STR00001##

wherein Y.sup.1 represents an aryl group, X.sup.2 represents a —O— group, a —NH— group, a —S— group, a —CO—NH— group, a —NH—CO—NH— group, a —NH—CO— group, a —CH(OH)— group, a —CH(COOH)NH— group, a —CH(COOCH.sub.3)NH— group, a —C(OH)(CH.sub.2OH)—, a

##STR00002##

group, a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or heteroatoms, a —SO.sub.2— group, or a —SO.sub.2—NH— group, Y.sup.2 represents a hydrogen atom, a hydroxyl group, a (C.sub.1-C.sub.4)alkoxy group, a —CHC(OH).sub.2, a COOR.sub.f, wherein R.sub.f represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, a morpholinyl group, a dihydropyranyl group, a

##STR00003##

group, a

##STR00004##

group, a —PO(OR.sub.f)(OR′.sub.f) group, wherein R.sub.f and R′.sub.f independently represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, an oxetanyl group, a —Si(CH.sub.3).sub.3 group, a —NHCOO—(C.sub.1-C.sub.4)alkyl group, or a —CR.sup.1R.sup.2R.sup.3 group, or any of its pharmaceutically acceptable salt and pharmaceutical compositions containing them and to synthesis process for manufacturing them.