University Of Saarland Work Values

Daily Duties at University Of Saarland:

Hydroxy Steroid Dehydrogenase Type 1 Inhibitors: Discovery of selective inhibitors of 17B-hydroxysteroid dehydrogenase type 1 (17ß-HSD1), a steroidogenic enzyme catalyzing the formation of the most active estrogen Estradiol (E2). E2 plays a key role in the proliferation of cancer cells and the growth of endometriosis. Selective inhibition of 17ß-HSD1 could thus be a novel and promising strategy for the treatment of this disease. Starting from the three-dimensional structures of both the protein and its substrate E1 we were able to derive a pharmacophore model which led to the discovery of highly potent non-steroidal inhibitors of 17 β –HSD1. Structural information in the ligand binding sites of the estrogen receptors (α and ß) was used to avoid estrogenicity of the compounds. 2-Bromonaphthalenes were formylated at 6-position. The resulting formyl derivatives subjected to Suzuki coupling using aryl boronic acids to afford 2-aryl-6-formyl naphthalenes which were oxidized to corresponding acids. These naphthoic acids activated to corresponding acid chlorides. These acid chlorides reacted with different heterocyclic amines to afford 2-methoxy-6-(3-methoxyphenyl)-N(heteroaryl)-1-amide which were reacted with boron tribromide to furnish the title compounds 2-hydroxy-6-(3-hydroxyphenyl)-N-(heteroaryl)-1-naphthamides. 6-(3-hydroxyphenyl)-1-(phenylsulfanyl)-2-naphthols which were prepared by reacting 2-(3-hydroxyphenyl)-6-bromonaphthalenes with appropriate aryl mercaptans. 6-(3-hydroxyphenyl)-1-(phenylsulfonyl)-2-naphthols then oxidized to 6-(3-hydroxyphenyl)-1-(phenylsulfanyl)-2-naphthols using m-CPBA. These molecules found to be very potent inhibitors of 17ßHSD1. These new scaffolds entered in to phase-3 clinical trials, waiting to be launched in to the market. Thirty seven novel non-steroidal substituted 6-phenyl-2-naphthols were synthesized and evaluated for 17β-HSD1 inhibition, selectively toward 17β-HSD2 and the estrogen receptors (ERs) α and β and pharmacokinetic properties. SAR studies revealed that the compounds most likely bind according to binding mode B to the active site, i.e., the 6-phenyl moiety mimicking the steroidal A-ring. While substitution at the phenyl ring decreased activity, introduction of substituents at the naphthol moiety led to highly active compounds, especially in position 1. The 6-(3-hydroxyphenyl)-1-phenyl-2-naphthol showed a very high inhibitory activity for 17 βHSD1 (IC50=20 nM) and good selectivity (17b-HSD2 and ERs) and pharmacokinetic properties after peroral application

What they like about University Of Saarland:

Working in an organization that is technologically advanced, creative, and innovative is critical in your assessment of hiring companies. Less important to you are stability of the organization, the length of time an organization has been in business, and the business' plans for the future. You prefer a fast-moving company that will take risks to achieve its goals and objectives. The length of time the company has been in business is irrelevant. Maintaining status quo is unnecessary. You thrive on change, uncertainty and the upside of potential business risks, especially those associated with innovation. Stability for the long haul is not nearly as important as is working in an atmosphere that is charged with a sense of urgency and constant change.

Tags

synthetic chemist, medicinal chemist, lab technician, QC chemist, Analytical chemist

Skills

P&L responsibilities, Presentation, Ecommerce Strategy and digital marketing channels optimization - SEO, SEM, email, affiliates - for high-profile accounts., Technology Solutions, Sales Support, Software Implementation, Requirements Analysis & Specification, Leadership , Planning and executing organic synthesis in stipulated time, World wide literature survey , Purification, isolation of the crude compounds using chromatographic techniques, Use of HPLC, GC-MS, UV, NMR, FTIR for characterizing the compounds, Interpretation of the spectral data, proposing the mechanisms for product and byproduct formation, Microsoft Word, Excel, Chemdraw package , Writing the manuscripts, power point presentations, Omega software, LIMS, Speaker experience on hte world stage, Reviewing the manuscripts, Completing the projects within holding times to the customer satisfaction with high productivity

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