Synthesis and computational analysis of conformationally restricted [3.2.2]- and [3.2.1]-3-azabicyclic diamines

Sreedhar Reddy Tummalapalli, Rohit Bhat, Craig Waitt, Hendrik Eshuis, David Rotella

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Conformational restriction is a useful approach for ligand design in organic and medicinal chemistry. This manuscript reports the facile synthesis and in silico conformational analysis of two new diastereomeric [3.2.2]-3-azabicyclic, two new [3.2.1]-3-aza-8-oxy-bicyclic and one new [3.2.1]-3-azabicyclic diamine scaffolds. A conformational analysis of these structures along with calculation of carbon–carbon/carbon–nitrogen bond angles was carried out and compared to those in the flexible 1,3-diaminopropane template upon which they were based. It is of particular importance that these scaffolds have bond lengths and angles that can overlap with low energy conformers of the flexible diamine. Such information is useful for ligand design in organic chemistry and for development of structure activity relationships and in silico screening in medicinal chemistry.

Original languageEnglish
Pages (from-to)4087-4089
Number of pages3
JournalTetrahedron Letters
Volume58
Issue number43
DOIs
StatePublished - 1 Jan 2017

Fingerprint

Organic Chemistry
Diamines
Pharmaceutical Chemistry
Scaffolds
Computer Simulation
Ligands
Bond length
Structure-Activity Relationship
Screening
trimethylenediamine

Keywords

  • Computational analysis
  • Conformational restriction
  • Diamines

Cite this

@article{de2a8eef98424d7a96a8a78d63fcd032,
title = "Synthesis and computational analysis of conformationally restricted [3.2.2]- and [3.2.1]-3-azabicyclic diamines",
abstract = "Conformational restriction is a useful approach for ligand design in organic and medicinal chemistry. This manuscript reports the facile synthesis and in silico conformational analysis of two new diastereomeric [3.2.2]-3-azabicyclic, two new [3.2.1]-3-aza-8-oxy-bicyclic and one new [3.2.1]-3-azabicyclic diamine scaffolds. A conformational analysis of these structures along with calculation of carbon–carbon/carbon–nitrogen bond angles was carried out and compared to those in the flexible 1,3-diaminopropane template upon which they were based. It is of particular importance that these scaffolds have bond lengths and angles that can overlap with low energy conformers of the flexible diamine. Such information is useful for ligand design in organic chemistry and for development of structure activity relationships and in silico screening in medicinal chemistry.",
keywords = "Computational analysis, Conformational restriction, Diamines",
author = "Tummalapalli, {Sreedhar Reddy} and Rohit Bhat and Craig Waitt and Hendrik Eshuis and David Rotella",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.tetlet.2017.09.033",
language = "English",
volume = "58",
pages = "4087--4089",
journal = "Tetrahedron Letters",
issn = "0040-4039",
publisher = "Elsevier Ltd",
number = "43",

}

Synthesis and computational analysis of conformationally restricted [3.2.2]- and [3.2.1]-3-azabicyclic diamines. / Tummalapalli, Sreedhar Reddy; Bhat, Rohit; Waitt, Craig; Eshuis, Hendrik; Rotella, David.

In: Tetrahedron Letters, Vol. 58, No. 43, 01.01.2017, p. 4087-4089.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Synthesis and computational analysis of conformationally restricted [3.2.2]- and [3.2.1]-3-azabicyclic diamines

AU - Tummalapalli, Sreedhar Reddy

AU - Bhat, Rohit

AU - Waitt, Craig

AU - Eshuis, Hendrik

AU - Rotella, David

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Conformational restriction is a useful approach for ligand design in organic and medicinal chemistry. This manuscript reports the facile synthesis and in silico conformational analysis of two new diastereomeric [3.2.2]-3-azabicyclic, two new [3.2.1]-3-aza-8-oxy-bicyclic and one new [3.2.1]-3-azabicyclic diamine scaffolds. A conformational analysis of these structures along with calculation of carbon–carbon/carbon–nitrogen bond angles was carried out and compared to those in the flexible 1,3-diaminopropane template upon which they were based. It is of particular importance that these scaffolds have bond lengths and angles that can overlap with low energy conformers of the flexible diamine. Such information is useful for ligand design in organic chemistry and for development of structure activity relationships and in silico screening in medicinal chemistry.

AB - Conformational restriction is a useful approach for ligand design in organic and medicinal chemistry. This manuscript reports the facile synthesis and in silico conformational analysis of two new diastereomeric [3.2.2]-3-azabicyclic, two new [3.2.1]-3-aza-8-oxy-bicyclic and one new [3.2.1]-3-azabicyclic diamine scaffolds. A conformational analysis of these structures along with calculation of carbon–carbon/carbon–nitrogen bond angles was carried out and compared to those in the flexible 1,3-diaminopropane template upon which they were based. It is of particular importance that these scaffolds have bond lengths and angles that can overlap with low energy conformers of the flexible diamine. Such information is useful for ligand design in organic chemistry and for development of structure activity relationships and in silico screening in medicinal chemistry.

KW - Computational analysis

KW - Conformational restriction

KW - Diamines

UR - http://www.scopus.com/inward/record.url?scp=85029584895&partnerID=8YFLogxK

U2 - 10.1016/j.tetlet.2017.09.033

DO - 10.1016/j.tetlet.2017.09.033

M3 - Article

VL - 58

SP - 4087

EP - 4089

JO - Tetrahedron Letters

JF - Tetrahedron Letters

SN - 0040-4039

IS - 43

ER -