{"id":25642,"date":"2015-09-29T12:47:38","date_gmt":"2015-09-29T19:47:38","guid":{"rendered":"https:\/\/hepatochem.com\/methyl-magic-medicinal-chemistry\/"},"modified":"2015-09-29T12:47:38","modified_gmt":"2015-09-29T19:47:38","slug":"methyl-magic-medicinal-chemistry","status":"publish","type":"post","link":"https:\/\/hepatochem.com\/euro\/methyl-magic-medicinal-chemistry\/","title":{"rendered":"Magic methyl in medicinal chemistry"},"content":{"rendered":"


\n<\/p>\n

[et_pb_section fb_built=”1″ _builder_version=”3.22″ global_colors_info=”{}”][et_pb_row _builder_version=”3.25″ background_size=”initial” background_position=”top_left” background_repeat=”repeat” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text _builder_version=”3.27.4″ background_size=”initial” background_position=”top_left” background_repeat=”repeat” global_colors_info=”{}”]<\/p>\n

<\/h6>\n

Methyl groups are very common in drug molecules. As reported by Heike Schonherr and Tim Cernak1<\/sup>, more than half of the top-selling drugs contains a CH3<\/sub>. A simple substitution of a C-H with a methyl can increase the potency of a compound by more than 100-fold.<\/p>\n

The effect of C-H methylation primarily affects the conformation of the original molecule. Based on this reported statistical analysis2<\/sup> the effect of methyl can be equally positive or negative. However a positive effect could be decisive in a drug discovery program.<\/p>\n

Effect of ortho substitution3,4<\/sup>.<\/p>\n

\"ortho_methylation1\"<\/p>\n

\"ortho_methylation2\"<\/p>\n

Effect of ring substitution5<\/sup><\/p>\n

\"ring_methylation\"<\/p>\n

Effect on rotatable bond6<\/sup><\/p>\n

\"bond_methylation\"<\/p>\n

Even if the methyl can be seen as a potential hot spot for metabolism. The addition of the methyl next to a metabolism position can improve metabolic stability.7<\/sup><\/p>\n

\"Methyl_stability\"<\/p>\n

 <\/p>\n

Contact us at info@hepatochem.com<\/p>\n

 <\/p>\n

    \n
  1. Heike Schonherr and Tim Cernak, Angew. Chem Int. Ed. 2013, 52, 12256-12267<\/li>\n
  2. C. S. Leung, S. S. F. Leung, J. Tirado-Rives, W. L. Jorgensen, J. Med. Chem. 2012, 55, 4489 \u2013 4500.<\/li>\n
  3. F. Berardi, C. Abate, S. Ferorelli, A. F. de Robertis, M. Leopoldo, N.A. Colabufo, M. Niso, R. Perrone, J. Med. Chem. 2008, 51, 7523 \u2013 7531.<\/li>\n
  4. J. Y. Hwang, D. Smithson, F. Zhu, G. Holbrook,M. C. Connelly, M. Kaiser, R. Brun, R. K. Guy, J. Med. Chem. 2013, 56, 2850 \u2013 2860.<\/li>\n
  5. P. J. Coleman and coll<\/i>. , Chem- MedChem 2012, 7, 415 \u2013 424.<\/li>\n
  6. G. F. Costello, R. James, J. S. Shaw, A.M. Slater, N. C. J. Stutchbury, J. Med. Chem. 1991, 34, 181 \u2013 189.<\/li>\n
  7. R.W. Friesen and coll.<\/i>, Bioorg. Med. Chem. Lett. 1998, 8, 2777 \u2013 2782.<\/li>\n<\/ol>\n

     <\/p>\n

     
    \n[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/body><\/html><\/p>\n","protected":false},"excerpt":{"rendered":"

    Methyl groups are very common in drug molecules. As reported by Heike Schonherr and Tim Cernak1, more than half of the top-selling drugs contains a CH3. A simple substitution of a C-H with a methyl can increase the potency of a compound by more than 100-fold. The effect of C-H methylation primarily affects the conformation […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"

    \u00a0<\/h6>

    Methyl groups are very common in drug molecules. As reported by Heike Schonherr and Tim Cernak1<\/sup>, more than half of the top-selling drugs contains a CH3<\/sub>. A simple substitution of a C-H with a methyl can increase the potency of a compound by more than 100-fold.<\/p>

    The effect of C-H methylation primarily affects the conformation of the original molecule. \u00a0Based on this reported statistical analysis2<\/sup> the effect of methyl can be equally positive or negative. However a positive effect could be decisive in a drug discovery program.<\/p>

    Effect of ortho substitution3,4<\/sup>.<\/p>

    \"ortho_methylation1\"<\/p>

    \"ortho_methylation2\"<\/p>

    Effect of ring substitution5<\/sup><\/p>

    \"ring_methylation\"<\/p>

    Effect on rotatable bond6<\/sup><\/p>

    \"bond_methylation\"<\/p>

    Even if the methyl can be seen as a potential hot spot for metabolism. The addition of the methyl next to a metabolism position can improve metabolic stability.7<\/sup><\/p>

    \"Methyl_stability\"<\/p>

    \u00a0<\/p>

    Contact us at info@hepatochem.com<\/p>

    \u00a0<\/p>

    1. Heike Schonherr and Tim Cernak, Angew. Chem Int. Ed. 2013, 52, 12256-12267<\/li>
    2. C. S. Leung, S. S. F. Leung, J. Tirado-Rives, W. L. Jorgensen, J. Med. Chem. 2012, 55, 4489 \u2013 4500.<\/li>
    3. F. Berardi, C. Abate, S. Ferorelli, A. F. de Robertis, M. Leopoldo, N.A. Colabufo, M. Niso, R. Perrone, J. Med. Chem. 2008, 51, 7523 \u2013 7531.<\/li>
    4. J. Y. Hwang, D. Smithson, F. Zhu, G. Holbrook,M. C. Connelly, M. Kaiser, R. Brun, R. K. Guy, J. Med. Chem. 2013, 56, 2850 \u2013 2860.<\/li>
    5. P. J. Coleman and coll<\/i>. , Chem- MedChem 2012, 7, 415 \u2013 424.<\/li>
    6. G. F. Costello, R. James, J. S. Shaw, A.M. Slater, N. C. J. Stutchbury, J. Med. Chem. 1991, 34, 181 \u2013 189.<\/li>
    7. R.W. Friesen and coll.<\/i>, Bioorg. Med. Chem. Lett. 1998, 8, 2777 \u2013 2782.<\/li><\/ol>

      \u00a0<\/p>

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