Synthesis and properties of 1,3-disubstituted ureas and their isosteric analogues containing polycyclic fragments: XX. 1-[(3,5-difluoroadamantan-1-yl)]-3-R-ureas and symmetric diureas

Capa

Citar

Texto integral

Acesso aberto Acesso aberto
Acesso é fechado Acesso está concedido
Acesso é fechado Somente assinantes

Resumo

A method has been developed for the production of (3,5-difluoroadamantan-1-yl) isocyanate from 3,5-difluoroadamantan-1 carboxylic acid and diphenyphosphoryl azide, using a new fluorinating agent, the Ishikawa reagent, at one of the synthesis stages. Reaction of (3,5- difluoroadamantane-1-yl)isocyanate with aliphatic diamines and trans-4-amino(cyclohexyloxy)A series of 1,3-disubstituted urea and dimourea with yields of 43-96% was synthesized with benzoic acid. By hydrolysis of (3,5-difluoroadamantan-1-yl)isocyanate in the presence of catalytic amounts of DBU, a symmetrical 1,3-bis(3,5-difluoroadamantan-1-yl) was obtainedurea with a yield of 47%.The influence of the number of fluorine atoms in the adamantile substituent on the melting temperatures and lipophilicity of urea has been established, which makes it possible to purposefully regulate these important properties of urea as potential enzyme inhibitors.

Texto integral

Acesso é fechado

Sobre autores

B. Gladkikh

Volgograd State Technical University

Email: butov@post.volpi.ru
ORCID ID: 0000-0001-6271-0479
Rússia, prosp. Lenina 28, Volgograd, 400005

D. Danilov

Volgograd State Technical University

Email: butov@post.volpi.ru
ORCID ID: 0000-0001-8734-2617
Rússia, prosp. Lenina 28, Volgograd, 400005

V. Dyachenko

Volgograd State Technical University; VSTU

Email: butov@post.volpi.ru
ORCID ID: 0000-0002-6209-7106

Volzhsky polytechnic institute (branch) VSTU

Rússia, prosp. Lenina 28, Volgograd, 400005; ul. Engelsa 42a, Volzhsky, 404121

V. Burmistrov

Volgograd State Technical University

Email: butov@post.volpi.ru
ORCID ID: 0000-0002-8547-9166
Rússia, prosp. Lenina 28, Volgograd, 400005

G. Butov

Volgograd State Technical University; VSTU

Autor responsável pela correspondência
Email: butov@post.volpi.ru
ORCID ID: 0000-0002-0839-4513

Volzhsky polytechnic institute (branch) VSTU

Rússia, prosp. Lenina 28, Volgograd, 400005; ul. Engelsa 42a, Volzhsky, 404121

I. Novakov

Volgograd State Technical University

Email: butov@post.volpi.ru
ORCID ID: 0000-0002-0980-6591
Rússia, prosp. Lenina 28, Volgograd, 400005

Bibliografia

  1. Бурмистров В.В., Кузнецов Я.П., Новиков В.В., Аббас Саиф М.Х., Давиденко А.В., Вернигора А.А., Бутов Г.М., ЖОрХ, 2023, 59, ХХХ–ХХХ [Burmistrov V.V. Kuznetsov Y.P., Novikov V.V., Abbas Saeef M.H., Davidenko A.V., Vernigora A.A., Butov G.M. Russ. J. Org. Chem. (Engl. Transl.), 2023, 59, XXX–XXX]. Meanwell N.A. J. Med. Chem., 2018, 61, 5822–5880. doi: 10.1021/acs.jmedchem.7b01788
  2. Richardson P. Expert Opin. Drug Discov., 2021, 16, 1261–1286. doi: 10.1080/17460441.2021.1933427
  3. Hwang S.H., Wecksler A.T., Zhang G., Morisseau C., Nguyen L.V., Fu S.H., Hammock B.D., Bioorg. Med. Chem. Lett., 2013, 23, 3732–3737. doi: 10.1016/j.bmcl.2013.05.011
  4. Codony S., Valverde E., Leiva R., Brea J., Loza M.I., Morisseau C., Hammock B.D., Vázquez S. Bioorg. Med. Chem. 2019, 27, 115078. doi: 10.1016/j.bmc.2019.115078
  5. Бурмистров В.В., Бутов Г.М., Дьяченко В.С. ЖОрХ, 2017, 53, 965–968 [Burmistrov, V.V., Butov, G.M., D’yachenko, V.S. Russ. J. Org. Chem. (Engl. Transl.), 2017, 53, 977–980]. doi: 16.1134/S107042801707003X
  6. Lee K.S.S., Liu J.-Y., Wagner K.M., Pakhomova S., Dong H., Morisseau C., Fu S.H., Yang J., Wang P., Ulu A., Mate C.A., Nguyen L.V., Hwang S.H., Edin M.L., Mara A.A., Wulff H., Newcomer M.E., Zeldin D.C., Hammock B.D. J. Med. Chem., 2014, 57, 7016–7030. doi: 10.1021/jm500694p
  7. Anandan S.-K., Webb H.K., Chen D., Wang Yi-X. (J.), Aavula B.R., Cases S., Cheng Yi., Do Z.N., Mehra U., Tran V., Vincelette J., Waszczuk J., White K., Wong K.R., Zhang Le-N., Jones P.D., Hammock B.D., Patel D.V., Whitcomb R., MacIntyre D.Eu., Sabry J., Gless R. Bioorg. Med. Chem. Lett., 2011, 21, 983–988. doi: 10.1016/j.bmcl.2010.12.042
  8. Wilkinson Sh.M., Barron M.L., O’Brien-Brown J., Jans-sen B., Stokes L., Werry E.L., Chishty M., Skarratt K K., Ong J.A., Hibbs D.E., Vugts D.J., Fuller S., Windhorst A.D., Kassiou M. ACS Chem. Neurosci., 2017, 8, 2374–2380. doi: 10.1021/acschemneuro.7b00272
  9. Данилов Д.В., Дьяченко В.С., Бурмистров В.В. Бутов Г.М., Новаков И.А. Изв. АН. Сер. хим., 2022, 1, 107–113. [Danilov D.V., D'yachenko V.S., Burmistrov V.V., Butov G.M., Novakov I.A. Russ. Chem. Bull., Int. Ed. (Engl. Transl.), 2022, 1, 107–113.] doi: 10.1007/s11172-022-3383-8
  10. Гладких Б.П., Данилов Д.В., Дьяченко В.С., Бурмистров В.В., Бутов Г.М., Новаков И.А. Изв. АН. Сер. хим., 2022, 9, 1998–2005. [Gladkikh B.P., Danilov D.V., Dyachenko V.S., Burmistrov V.V., Butov G.M., Novakov I.A. Russ. Chem. Bull., Int. Ed. (Engl. Transl.), 2022, 9, 1998–2005.] doi: 10.1007/s11172-022-3620-1
  11. Jasys V. J., Lombardo F., Appleton T.A., Bordner J., Ziliox M., Volkmann R.A. J. Am. Chem. Soc. 2000, 3, 466–473. doi: 10.1021/ja992652x
  12. Бутов Г.М., Бурмистров В.В., Данилов Д.В., Питушкин Д.А., Мориссье К., Хэммок Б. Д., Изв. АН. Сер. хим., 2015, 64, 1569–1575 [Butov G.M., Burmistrov V.V., Danilov D.V., Pitushkin D.A., Morisseau C., Hammock B.D., Russ. Chem. Bull., 2015, 64, 1569-1575]. doi: 10.1007/s11172-015-1043-y

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar
2. Fig. 1. 1-(1-Acetylpiperidin-4-yl)-3-adamantan-1-yl urea (A) and its fluorinated analogs (B, C) are candidate compounds for clinical trials

Baixar (59KB)
Metadados
3. Fig. 2. Structures of P2X7 receptor antagonists containing an adamantyl substituent

Baixar (76KB)
Metadados
4. Scheme 1

Baixar (31KB)
Metadados
5. Scheme 2

Baixar (43KB)
Metadados
6. Scheme 3

Baixar (58KB)
Metadados
7. Scheme 4

Baixar (71KB)
Metadados
8. Scheme 5

Baixar (71KB)
Metadados
9. Fig. 3. Dependence of logP (Y axis) on the number of methylene bridges n (X axis) in diureas with different contents of fluorine atoms in the adamantyl substituent

Baixar (58KB)
Metadados
10. Fig. 4. Dependence of the melting temperature on the number of methylene bridges n in diureas with different contents of fluorine atoms in the adamantyl substituent F–Ad [11]

Baixar (67KB)
Metadados

Nota

Сообщение XIX см. [1].


Declaração de direitos autorais © Russian Academy of Sciences, 2024