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Chemical Optimization
Synthesis of 1-(Aryl-1H-pyrrolyl)(phenyl)methyl-1H-imidazole Derivatives as Antiprotozoal Agents

1-(Aryl-1H-pyrrolyl)(phenyl)methyl-1H-imidazole Derivatives - Antiprotozoal AgentsTrypanosomatid and plasmodium parasites are producing a great deal of chronic diseases and affecting hundreds of millions people mainly in developing countries. However, in the last years, such diseases are dramatically disseminating worldwide, due to some factors including vector and human migrations or co-infections in immunosuppressed patients. The current antiprotozoal therapies are unsatisfactory due to their low efficacy, high toxicity and appearance of resistant parasitic strains. Therefore, there is an speedy need to develop new antiprotozoal drugs.

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Synthesis of Arylpiperazines as Perspective Toxoplasma gondii Dihydrofolate Reductase Inhibitors

Arylpiperazines as Perspective T. gondii DHFR InhibitorsToxoplasmosis is a parasitic disease caused by Toxoplasma gondii. Approximately one-third of the population worldwide is chronically infected with T. gondii. First-line treatment of toxoplasmosis is a therapy based on dihydrofolate reductase (DHFR, DHFRP1, DYR) inhibitors which act on the folate metabolic pathway, thereby inhibiting T. gondii proliferation and survival.

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Synthesis of Styryl-phenyl-ureas as Dual-targeted Inhibitors of PD-L1 and VEGFR-2

Styryl-phenyl-ureas as Perspective Inhibitors of PD-L1 and VEGFR-2Programmed death-ligand 1 (PD-L1, cluster of differentiation 274, CD274, B7 homolog 1 or B7-H1) is a transmembrane protein that plays a major role in suppressing the adaptive arm of immune system during particular events such as tissue allografts, pregnancy, autoimmune disease and some other pathological disease states. Upregulation of PD-L1 may allow cancers to evade the host immune system.

Vascular endothelial growth factor receptor 2 (VEGFR-2, Kinase insert domain receptor, KDR, CD309, FLK1) is a VEGF receptor that plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Abnormal functioning of VEGFR-2 is associated with cancer.

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Synthesis of Novel Derivatives of NMDARs Allosteric Modulators

Syntheses of novel allosteric modulators of NMDARsN-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels wich is activated by L-glutamate (the brain’s primary excitatory neurotransmitter). They have many critical roles in CNS function and in various neurological and psychiatric disorders.

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Synthesis of Tetrahydroisoquinoline Derivatives as Perspective Inhibitors of P-glycoprotein 1

Tetrahydroisoquinoline Derivatives as Perspective Inhibitors of P-glycoprotein 1P-glycoprotein 1 (P-gp, Pgp, multidrug resistance protein 1, MDR1, ATP-binding cassette sub-family B member 1, ABCB1, cluster of differentiation 243 or CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells. It is an ATP-dependent efflux pump with broad substrate specificity wich evolved as a defense mechanism against harmful substances. But at the same time it pumps many drugs, including anticancer chemotherapeutics, from the cell thereby weakening their action. Consequently, P-gp overexpression is one of the main mechanisms behind decreased intracellular drug accumulation and development of multidrug resistance.

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