291775-59-2Relevant articles and documents
Design, Synthesis and Biological Evaluation of Neogliptin, a Novel 2-Azabicyclo[2.2.1]heptane-Based Inhibitor of Dipeptidyl Peptidase-4 (DPP-4)
Dahlén, Amelia D.,Gureev, Maxim A.,Kirichenko, Olga G.,Maslov, Ivan O.,Porozov, Yuri B.,Schi?th, Helgi B.,Shorshnev, Sergey V.,Trukhan, Mikhail V.,Trukhan, Vladimir M.,Tuaeva, Natalya O.,Zinevich, Tatiana V.
, (2022/03/02)
Compounds that contain (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid substituted with bicyclic amino moiety (2-aza-bicyclo[2.2.1]heptane) were designed using molecular modelling methods, synthesised, and found to be potent DPP-4 (dipeptidyl peptidase-4) inhibitors. Compound 12a (IC50 = 16.8 ± 2.2 nM), named neogliptin, is a more potent DPP-4 inhibitor than vildagliptin and sitagliptin. Neogliptin interacts with key DPP-4 residues in the active site and has pharmacophore parameters similar to vildagliptin and sitagliptin. It was found to have a low cardiotoxic effect compared to sitagliptin, and it is superior to vildagliptin in terms of ADME properties. Moreover, compound 12a is stable in aqueous solutions due to its low intramolecular cyclisation potential. These findings suggest that compound 12a has unique properties and can act as a template for further type 2 diabetes mellitus drug development.
PHOSPHONATE COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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, (2017/03/14)
Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula (I), or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is a phosphonate substituent (R32) are provided. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduces the excessive activation of complement.
ALKYNE COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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, (2017/03/14)
Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is alkyne substituent (R32) are provided. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein can reduce the excessive activation of complement.
COMPOUNDS FOR THE TREATMENT OF MEDICAL DISORDERS
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, (2017/03/14)
Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula (I), or a pharmaceutically acceptable salt or composition thereof The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduce the excessive activation of complement.
AMIDE COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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, (2017/03/14)
Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is an amide substituent (R32) are provided. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein are capable of reducing the excessive activation of complement.
ETHER COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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, (2017/03/14)
Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is an ether substituent (R32) are provided. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduce the excessive activation of complement.
ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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, (2017/03/14)
Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is an aryl, heteroaryl or heterocycle (R32) are provided. The inhibitors of Factor D described herein reduce the excessive activation of complement.
AMINO COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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Paragraph 0576; 0581; 0582, (2017/03/14)
Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is an amino substituent (R32) are provided. The inhibitors of Factor D described herein reduce the excessive activation of complement.
Preparation method of high-purity Ledipasvir intermediate
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, (2017/02/24)
The invention discloses a preparation method of a high-purity Ledipasvir intermediate (1R, 3S and 4S)-N-t-butylcarbonyl-2-azabicyalo[2.2.1] heptane-3-carboxylic acid. According to the method, (1R, 3S and 4S)-N-t-butylcarbonyl-2-azabicyalo[2.2.1] heptane-3-carboxylate serves as an initial raw material, and the Ledipasvir intermediate is obtained through enzymatic hydrolysis. A test proves that the high-purity Ledipasvir intermediate is obtained and a feasible path is provided for reducing production cost and improving drug use safety. Meanwhile, the method has the advantages that operation is easy, environment friendliness is achieved, the yield is high, selectivity is high and cost is low; large-scale production can be achieved, and industrial application and popularization are facilitated.
Novel l-prolyl-l-leucylglycinamide (PLG) tripeptidomimetics based on a 2-azanorbornane scaffold as positive allosteric modulators of the D2R
Sampaio-Dias, Ivo E.,Sousa, Carlos A. D.,García-Mera, Xerardo,Ferreira Da Costa, Joana,Caama?o, Olga,Rodríguez-Borges, José E.
supporting information, p. 11065 - 11069 (2016/12/09)
An efficient and straightforward orthogonal methodology was successfully developed to achieve constrained l-prolyl-l-leucylglycinamide (PLG) analogues starting from two proline mimetics based on a 2-azanorbornane scaffold. A preliminary dopamine D2 receptor radiolabeled binding assay with [3H]-N-propylnorapomorphine shows that enantiopurity of PLG peptidomimetics based on 2-azanorbornane is a requirement to achieve statistically significant positive modulators of the D2 receptor. This is the first documented active peptidomimetic of PLG whose bioactivity is not correlated with the C-terminal carboxamide pharmacophore and which cannot adopt the hypothesized type II β-turn conformation.
