The Mitsunobu reaction of some indan amino alcohols

Freedman, Jules; Vaal, Mark J.; Huber, Edward W.

doi:10.1021/jo00002a033

Cited by 41 publications

(24 citation statements)

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“…Trans geometries, in particular with aryloxy substituents (R5 = aryl), were selectively accessible by epoxide opening of indene oxide with amines (1.3 eq. amine in MeCN, reflux, 10-24 h) and a Mitsunobu reaction with double inversion via an aziridinium intermediate (Freedman et al, 1991) (Larrow et al, 1999). Detailed information and an explicit experimental pathway for the preparation of SAR7334 is provided in Supporting Information Fig.…”

Section: Chemistrymentioning

confidence: 99%

Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol‐sensitive TRPC cation channels

Maier

Follmann

Heßler

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSEThe cation channel transient receptor potential canonical (TRPC) 6 has been associated with several pathologies including focal segmental glomerulosclerosis, pulmonary hypertension and ischaemia reperfusion-induced lung oedema. We set out to discover novel inhibitors of TRPC6 channels and investigate the therapeutic potential of these agents. EXPERIMENTAL APPROACHA library of potential TRPC channel inhibitors was designed and synthesized. Activity of the compounds was assessed by measuring intracellular Ca 2+ levels. The lead compound SAR7334 was further characterized by whole-cell patch-clamp techniques. The effects of SAR7334 on acute hypoxic pulmonary vasoconstriction (HPV) and systemic BP were investigated. KEY RESULTS SAR7334 inhibited TRPC6, TRPC3 and TRPC7-mediated Ca2+ influx into cells with IC50s of 9.5, 282 and 226 nM, whereas TRPC4 and TRPC5-mediated Ca 2+ entry was not affected. Patch-clamp experiments confirmed that the compound blocked TRPC6 currents with an IC50 of 7.9 nM. Furthermore, SAR7334 suppressed TRPC6-dependent acute HPV in isolated perfused lungs from mice. Pharmacokinetic studies of SAR7334 demonstrated that the compound was suitable for chronic oral administration. In an initial short-term study, SAR7334 did not change mean arterial pressure in spontaneously hypertensive rats (SHR). CONCLUSIONS AND IMPLICATIONSOur results confirm the role of TRPC6 channels in hypoxic pulmonary vasoregulation and indicate that these channels are unlikely to play a major role in BP regulation in SHR. SAR7334 is a novel, highly potent and bioavailable inhibitor of TRPC6 channels that opens new opportunities for the investigation of TRPC channel function in vivo.

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Section: Chemistrymentioning

confidence: 99%

Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol‐sensitive TRPC cation channels

Maier

Follmann

Heßler

et al. 2015

British J Pharmacology

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“…The incoming amine nitrogen can, in principle, attack at C‐1 or C‐2 in the aziridinium chloride. But it is reported23 that the nucleophile attacks the benzylic carbon in the aziridinium intermediate during the reaction of phenols with aminoindanols. Hence the approach of the nitrogen of the amine will be preferably toward more electrophilic benzylic carbon (C‐1) (Scheme ) during the reactions leading to 1,2‐diamines in this work.…”

Section: Stereochemical Aspectsmentioning

confidence: 99%

Remarkable enantioselective α‐amination in 1‐phenyl‐2‐(n‐alkylamino)‐1‐propanol

et al. 2012

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“…Finally, 2d and 3d were prepared from 2c and 3c through the intermediacy of an aziridinium ion, [15] which was regioselectively ring-opened at the benzylic position with sodium p-nitrobenzoate. The corresponding ester was reduced with DIBALH to furnish the desired trans-2-dialkylamino-1-indanols (Scheme 5).…”

Section: Preparation Of 1d and Derivativesmentioning

confidence: 99%

Exploring Structural Diversity in Ligand Design: The Aminoindanol Case

et al. 2008

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A series of enantiopure ligands based on the aminoindanol scaffold, but differing in regio-and stereochemistry has been synthesized. These ligands have been conveniently derivatized and their catalytic efficiency in different enantioselective reactions has been screened to determine privileged candidates with respect to regio-and stereochemistry for each considered process. The nature of the amino substituent has been optimized for specific applications and this has led to the development of an efficient method for the preparation of bulky bicyclic amines by reductive amination.

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The Mitsunobu reaction of some indan amino alcohols

Cited by 41 publications

References 0 publications

Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol‐sensitive TRPC cation channels

Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol‐sensitive TRPC cation channels

Remarkable enantioselective α‐amination in 1‐phenyl‐2‐(n‐alkylamino)‐1‐propanol

Exploring Structural Diversity in Ligand Design: The Aminoindanol Case

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