350236-32-7

Upstream product

• 40757-09-3 methyl 2-methoxy-5-iodobenzoate 

Downstream Products

• 1147116-75-3 (E)-3-chloro-2-methoxy-5-[1-(3-methoxy-7-methylbenzo[d]isoxazol-5-yl)-4-(2-oxy-oxazolidin-3-yl)-but-1-enyl]-benzoic acid methyl ester 
• 350236-34-9 3-chloro-5-iodo-2-methoxybenzoic acid 

Relevant academic research and scientific papers

Solid-phase synthesis of the alkenyldiarylmethane (ADAM) series of non-nucleoside HIV-1 reverse transcriptase inhibitors

The Sonogashira and Stille cross-coupling reactions have been employed in the synthesis of several non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the alkenyldiarylmethane (ADAM) series. The synthesis has been carried out both in solution and on a solid support. In contrast to previous syntheses of NNRTIs in the ADAM series, the present strategy allows the incorporation of differently substituted aromatic rings in a stereochemically defined fashion. The most potent of the new ADAMs inhibited the cytopathic effect of HIV-1RF in CEM-SS cell culture with an EC50 value of 20 nM.

Structure-based optimization and biological evaluation of human 20α-hydroxysteroid dehydrogenase (AKR1C1) salicylic acid-based inhibitors

The tertiary structure of the Leu308Val mutant of human 20α-hydroxysteroid dehydrogenase (AKR1C1) in complex with the inhibitor 3,5-dichlorosalicylic acid (DCL) has been determined. Structures and kinetic properties of the wild-type and mutant enzymes indicate that Leu308 is a selectivity determinant for inhibitor binding. The Leu308Val mutation resulted in 13-fold and 3-fold reductions in the inhibitory potencies of DCL and 3-bromo-5-phenylsalicylic acid (BPSA), respectively. The replacement of Leu308 with an alanine resulted in 473-fold and 27-fold reductions in the potencies for DCL and BPSA, respectively. In our attempts to optimize inhibitor potency and selectivity we synthesized 5-substituted 3-chlorosalicylic acid derivatives, of which the most potent compound, 3-chloro-5-phenylsalicylic acid (Ki = 0.86 nM), was 24-fold more selective for AKR1C1 relative to the structurally similar 3α-hydroxysteroid dehydrogenase (AKR1C2). Furthermore, the compound inhibited the metabolism of progesterone in AKR1C1-overexpressed cells with an IC50 value equal to 100 nM.

Alkenyldiarylmethanes, Fused Analogs And Syntheses Thereof

Non-nucleoside inhibitors of HIV-1 reverse transcriptase are described. Such inhibitors may be used as part of a combination therapy to treat HIV infection. Compounds described herein exhibit antiviral potency. In addition, compounds described herein exhibit metabolic stability. Also described herein are processes for preparing Non-nucleoside inhibitors of HIV-1 reverse transcriptase.

Synthesis, anti-HIV activity, and metabolic stability of new alkenyldiarylmethane HIV-1 non-nucleoside reverse transcriptase inhibitors

Non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) are part of the combination therapy currently used to treat HIV infection. Based on analogy with known HIV-1 NNRT inhibitors, 18 novel alkenyldiarylmethanes (ADAMs) containing 5-chloro-2-methoxyphenyl, 3-cyanophenyl, or 3-fluoro-5- trifluoromethylphenyl groups were synthesized and evaluated as HIV inhibitors. Their stabilities in rat plasma have also been investigated. Although introducing 5-chloro-2-methoxyphenyl or 3-fluoro-5-trifluoromethylphenyl groups into alkenyldiarylmethanes does not maintain the antiviral potency, the structural modification of alkenyldiarylmethanes with a 3-cyanophenyl substituent can be made without a large decrease in activity. The oxazolidinonyl group was introduced into the alkenyldiarylmethane framework and found to confer enhanced metabolic stability in rat plasma.