Identification of highly potent and selective HTRA1 inhibitors.

High temperature requirement A serine peptidase 1 (HTRA1) is a serine protease involved in an array of signaling pathways. It is also responsible for the regulation of protein aggregates via refolding, translocation, and degradation. It has subsequently been found that runaway proteolytic HTRA1 activity plays a role in a variety of diseases, including Age-Related Macular Degeneration (AMD), osteoarthritis, and Rheumatoid Arthritis.

Structure-based phylogeny identifies avoralstat as a TMPRSS2 inhibitor that prevents SARS-CoV-2 infection in mice.

Drugs targeting host proteins can act prophylactically to reduce viral burden early in disease and limit morbidity, even with antivirals and vaccination. Transmembrane serine protease 2 (TMPRSS2) is a human protease required for SARS coronavirus 2 (SARS-CoV-2) viral entry and may represent such a target. We hypothesized that drugs selected from proteins related by their tertiary structure, rather than their primary structure, were likely to interact with TMPRSS2.

Peptidomimetics Therapeutics for Retinal Disease.

Ocular disorders originating in the retina can result in a partial or total loss of vision, making drug delivery to the retina of vital importance. However, effectively delivering drugs to the retina remains a challenge for ophthalmologists due to various anatomical and physicochemical barriers in the eye. This review introduces diverse administration routes and the accordant pharmacokinetic profiles of ocular drugs to aid in the development of safe and efficient drug delivery systems to the retina with a focus on peptidomimetics as a growing class of retinal drugs, which have great therapeutic potential and a high degree of specificity.

Noncanonical Cation-π Cyclizations of Alkylidene β-Ketoesters: Synthesis of Spiro-fused and Bridged Bicyclic Ring Systems.

Three cation-π cyclization cascades initiated at alkylidene β-ketoesters bearing pendent alkenes are described. Depending upon the alkene substitution pattern and the reaction conditions employed, it is possible to achieve selective synthesis of the three different types of products, including 1-halo-3-carbomethoxycyclohexanes, spiro-fused tricyclic systems, and [4.3.

Two cadmium coordination polymers with bridging acetate and phenyl-enedi-amine ligands that exhibit two-dimensional layered structures.

Poly[tetra-μ-acetato-κ:'-bis-(μ-benzene-1,2-di-amine-κ:')dicadmium], [Cd(CHCOO)(CHN)] , (I), and poly[[(μ-acetato-κ:')(acetato-κ,')(μ-benzene-1,3-di-amine-κ:')cadmium] hemihydrate], {[Cd(CHCOO)(CHN)]·0.5HO} , (II), have two-dimensional polymeric structures in which monomeric units are joined by bridging acetate and benzenedi-amine ligands. Each of the Cd ions has an ON coordination environment.

Crystal structures of three lead(II) acetate-bridged di-amino-benzene coordination polymers.

Poly[tris-(acetato-κ(2) O,O')(μ2-acetato-κ(3) O,O':O)tetra-kis-(μ3-acetato-κ(4) O,O':O:O')bis-(benzene-1,2-di-amine-κN)tetra-lead(II)], [Pb4(CH3COO)8(C6H8N2)2] n , (I), poly[(acetato-κ(2) O,O')(μ3-acetato-κ(4) O,O':O:O')(4-chloro-benzene-1,2-diamine-κN)lead(II)], [Pb(CH3COO)2(C6H7ClN2)] n , (II), and poly[(κ(2) O,O')(μ3-acetato-κ(4) O,O':O:O')(3,4-di-amino-benzo-nitrile-κN)lead(II)], [Pb(CH3COO)2(C7H7N3)] n , (III), have polymeric structures in which monomeric units are joined by bridging acetate ligands. All of the Pb(II) ions exhibit hemidirected coordination. The repeating unit in (I) is composed of four Pb(II) ions having O6, O6N, O7 and O6N coordination spheres, respectively, where N represents a monodentate benzene-1,2-di-amine ligand and O acetate O atoms.

Poly[[tris-(μ2-acetato-κ(2) O:O')(4-chloro-benzene-1,2-di-amine-κN)(μ3-hydroxido)dizinc] ethanol monosolvate].

The title compound, {[Zn2(CH3CO2)3(OH)(C6H7ClN2)]·C2H5OH} n , has alternating octa-hedrally and tetra-hedrally coordinated Zn(2+) ions. The octa-hedral coordination sphere is composed of one N atom of the monodentate di-amino-chloro-benzene ligand, three acetate O atoms and two bridging hydroxide ligands. The tetra-hedral coordination sphere consists of three acetate O atoms and the hydroxide ligand.

Hydrogen bonding in 4-nitrobenzene-1,2-diamine and two hydrohalide salts.

The structures of 4-nitrobenzene-1,2-diamine [C6H7N3O2, (I)], 2-amino-5-nitroanilinium chloride [C6H8N3O2(+)·Cl(-), (II)] and 2-amino-5-nitroanilinium bromide monohydrate [C6H8N3O2(+)·Br(-)·H2O, (III)] are reported and their hydrogen-bonded structures described. The amine group para to the nitro group in (I) adopts an approximately planar geometry, whereas the meta amine group is decidedly pyramidal. In the hydrogen halide salts (II) and (III), the amine group meta to the nitro group is protonated.

An ortho-rhom-bic polymorph of 3,4-di-amino-benzo-nitrile.

The title compound, C7H7N3, is an ortho-rhom-bic polymorph that crystallizes in the space group Pca21. The previously reported monoclinic form [Geiger & Parsons (2013 ▶) Acta Cryst. E69, o452] crystallizes in the space group P21/c (Z = 4).

3,4-Diamino-benzonitrile.

The non-H atoms in the structure of the title mol-ecule, C7H7N3, are almost coplanar (r.m.s.