At the Speed of Light: The Systematic Implementation of Photoredox Cross-Coupling Reactions for Medicinal Chemistry Research.

The adoption of new and emerging techniques in organic synthesis is essential to promote innovation in drug discovery. In this Perspective, we detail the strategy we used for the systematic deployment of photoredox-mediated, metal-catalyzed cross-coupling reactions in AbbVie's medicinal chemistry organization, focusing on topics such as assessment, evaluation, implementation, and accessibility. The comprehensive evaluation of photoredox reaction setups and published methods will be discussed, along with internal efforts to build expertise and photoredox high-throughput experimentation capabilities.

Ocular proteomic and transcriptomic changes with aging in a rabbit model of lensectomy with intraocular lens insertion.

Children that undergo intraocular surgery have an exaggerated postoperative response compared to adults that can result in significant postoperative challenges and reduced post-operative visual acuity. Rabbits were used as an animal model for investigating aging differences, treatment options, and surgical techniques for anterior chamber surgical interventions due to similarities in anterior chamber size and decreasing postoperative response with age. In our study, juvenile and adult rabbits underwent lensectomy with intraocular lens (IOL) insertion to determine how ocular RNA transcripts and proteins change with age.

Tissue Plasminogen Activator Effects on Fibrin Volume and the Ocular Proteome in a Juvenile Rabbit Model of Lensectomy.

Purpose: To investigate the use of tissue plasminogen activator (tPA) and its effects on the ocular proteome as a therapeutic intervention for postoperative inflammation and fibrin formation following intraocular lens (IOL) insertion in a juvenile rabbit model.

Methods: Twenty-six rabbits, 6 to 7 weeks old, underwent lensectomy with IOL insertion. Following examination on day 3, 100 µL of either 25 µg of recombinant rabbit tPA or balanced salt solution (control) was injected into the anterior chamber.

Expanding the Medicinal Chemist Toolbox: Comparing Seven C(sp)-C(sp) Cross-Coupling Methods by Library Synthesis.

Despite recent advances in the field of C(sp)-C(sp) cross-couplings and the accompanying increase in publications, it can be hard to determine which method is appropriate for a given reaction when using the highly functionalized intermediates prevalent in medicinal chemistry. Thus a study was done comparing the ability of seven methods to directly install a diverse set of alkyl groups on "drug-like" aryl structures via parallel library synthesis. Each method showed substrates that it excelled at coupling compared with the other methods.

Quantitative proteomic analysis of aqueous humor after rabbit lensectomy reveals differences in coagulation and immunomodulatory proteins.

Compared to adults, children experience increased postoperative scarring and inflammation following intraocular surgery. While the underlying causes of the exaggerated immune response in children are not understood, proteins play key roles in postoperative scarring and wound healing processes. To identify and quantify proteins associated with the robust postoperative immune response, this study applied quantitative proteomics approaches to a juvenile rabbit model of lensectomy with intraocular lens (IOL) insertion.

Synthesis of anti-1,3 Amino Alcohol Motifs via Pd(II)/SOX Catalysis with the Capacity for Stereodivergence.

We report the development of a Pd(II)/(±)-MeO-SOX/2,5-dimethylbenzoquinone system that enables unprecedented access to anti-1,3 amino alcohol motifs in good yields (33 substrates, avg. 66% isolated yield, >20:1 dr) and high selectivities (avg. 10:1 dr).

Assessing Retinal Structure in Patients with Parkinson's Disease.

Objective: The retina is an extension of the central nervous system (CNS), and ocular symptoms can precede manifestations of CNS disorders. Given that several neurodegenerative conditions that affect the brain exhibit ocular symptoms, the retina may be an accessible biomarker to monitor disease progression. Dopamine, the key neurotransmitter related to Parkinson's disease (PD), is contained in amacrine and interplexiform cells, which reside in specific retinal layers.

Use of a Juvenile Rabbit Animal Model to Evaluate Therapeutic Interventions for Postoperative Inflammation and Fibrin Formation After Lensectomy.

Purpose: We used the juvenile rabbit as a model for investigating therapeutic interventions for postoperative inflammation and fibrin formation following intraocular lens (IOL) insertion for management of pediatric cataracts.

Methods: Twelve 6- to 7-week-old, 600 to 900 g rabbits underwent bilateral clear-cornea lensectomy via irrigation and aspiration with IOL insertion. Following wound closure, enoxaparin 8 mg ( = 6 eyes), preservative-free triamcinolone 0.

Assessing photoreceptor structure in patients with traumatic head injury.

Objective: Previous work using adaptive optics scanning light ophthalmoscopy (AOSLO) imaging has shown photoreceptor disruption to be a common finding in head and ocular trauma patients. Here an expanded trauma population was examined using a novel imaging technique, split-detector AOSLO, to assess remnant cone structure in areas with significant disruption on confocal AOSLO imaging and to follow photoreceptor changes longitudinally.

Methods And Analysis: Eight eyes from seven subjects with head and/or ocular trauma underwent imaging with spectral domain optical coherence tomography, confocal AOSLO and split-detector AOSLO to assess foveal and parafoveal photoreceptor structure.

Findings in Persistent Retinopathy of Prematurity.

Background And Objective: To determine whether retinopathy of prematurity (ROP) that persists beyond a postmenstrual age (PMA) of 45 weeks has abnormalities that can be documented by fundus photography or fluorescein angiography (FA).

Patients And Methods: Fundus photographs and FAs were reviewed for all premature infants who underwent FA for persistent ROP after 45 weeks PMA.

Results: Of the 487 infants who were screened for ROP, 16 (3.

Cone structure in subjects with known genetic relative risk for AMD.

Purpose: Utilize high-resolution imaging to examine retinal anatomy in patients with known genetic relative risk (RR) for developing age-related macular degeneration (AMD).

Methods: Forty asymptomatic subjects were recruited (9 men, 31 women; age range, 51 to 69 years; mean age, 61.4 years).

Structural basis for selective small molecule kinase inhibition of activated c-Met.

The receptor tyrosine kinase c-Met is implicated in oncogenesis and is the target for several small molecule and biologic agents in clinical trials for the treatment of cancer. Binding of the hepatocyte growth factor to the cell surface receptor of c-Met induces activation via autophosphorylation of the kinase domain. Here we describe the structural basis of c-Met activation upon autophosphorylation and the selective small molecule inhibiton of autophosphorylated c-Met.