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Chemical Structure| 627-35-0 Chemical Structure| 627-35-0

Structure of 627-35-0

Chemical Structure| 627-35-0

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Product Citations

Product Citations

Berg, Kaja ; Hegde, Pooja ; Pujari, Venugopal ; Brinkmann, Marzena ; Wilkins, David Z. ; Parish, Tanya , et al.

Abstract: The electron transport chain (ETC) in the cell membrane consists of a series of redox complexes that transfer electrons from electron donors to acceptors and couples this electron transfer with the transfer of protons (H+) across a membrane. This process generates proton motive force which is used to produce ATP and a myriad of other functions and is essential for the long-term survival of Mycobacterium tuberculosis (Mtb), the causative organism of tuberculosis (TB), under the hypoxic conditions present within infected granulomas. Menaquinone (MK), an important carrier molecule within the mycobacterial ETC, is synthesized de novo by a cluster of enzymes known as the classic/canonical MK biosynthetic pathway. MenA (1,4-dihydroxy-2-naphthoate prenyltransferase), the antepenultimate enzyme in this pathway, is a verified target for TB therapy. In this study, we explored structure-activity relationships of a previously discovered MenA inhibitor scaffold, seeking to improve potency and drug disposition properties. Focusing our campaign upon three molecular regions, we identified two novel inhibitors with potent activity against MenA and Mtb (IC50 = 13-22 μM, GIC50 = 8-10 μM). These analogs also displayed substantially improved pharmacokinetic parameters and potent synergy with other ETC-targeting agents, achieving nearly complete sterilization of Mtb in combination therapy within two weeks in vivo. These new inhibitors of MK biosynthesis present a promising new strategy to curb the continued spread of TB.

Keywords: 1,4-dihydroxy-2-naphthoate prenyltransferase ; MenA ; MenA inhibitors ; Menaquinone ; Mtb ; Mycobacterium tuberculosis ; Piperidine derivatives ; SAR

Alternative Products

Product Details of [ 627-35-0 ]

CAS No. :627-35-0
Formula : C4H11N
M.W : 73.14
SMILES Code : CCCNC
MDL No. :MFCD00009361
InChI Key :GVWISOJSERXQBM-UHFFFAOYSA-N
Pubchem ID :12315

Safety of [ 627-35-0 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H314
Precautionary Statements:P210-P280-P305+P351+P338-P310
Class:3(8)
UN#:2733
Packing Group:

Application In Synthesis of [ 627-35-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 627-35-0 ]

[ 627-35-0 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 79-37-8 ]
  • [ 5585-96-6 ]
  • [ 627-35-0 ]
  • [ 77872-27-6 ]
  • 2
  • [ 389602-62-4 ]
  • [ 627-35-0 ]
  • [ 68957-94-8 ]
  • [ 389601-19-8 ]
YieldReaction ConditionsOperation in experiment
44% With 4-methyl-morpholine; In dichloromethane; EXAMPLE 14 N-methyl-N-propyl-3-(4'-trifluoromethylbiphenyl-2-carbonylamino)-benzoic acid amide Prepared analogously to Example 7 from 3-(4'-trifluoromethylbiphenyl-2-carbonylamino)-benzoic acid and N-methyl-propylamine in dichloromethane with the addition of propanephosphonic acid cycloanhydride and N-methylmorpholine. Yield:44% of theory Rf value:0.73 (silica gel; dichloromethane/ethanol=9:1)
 

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