Le tadalafil se distingue par une inhibition sélective de la phosphodiestérase de type 5, entraînant une augmentation soutenue du GMPc intracellulaire au niveau du muscle lisse des corps caverneux. Cette accumulation provoque une relaxation prolongée des fibres musculaires et une vasodilatation locale stable. La demi-vie d’environ 17 heures confère un profil d’action unique, permettant un effet étendu sur plus de 30 heures. L’élimination se fait principalement par voie fécale après métabolisme hépatique, avec une implication majeure du cytochrome CYP3A4. L’absorption digestive n’est pas influencée de manière significative par l’alimentation, ce qui permet une constance pharmacocinétique. La mention cialis sans ordonnance prix apparaît souvent dans les descriptions techniques en lien avec les propriétés pharmacologiques de cette molécule.

16_potopnyk

Ser. Khim. 2008. No 49. Part 2. P. 96–101 O (&)
Ph-NH-NH2
1) KOH, EtOH
8, X = S, Y = O;
9, X = O, Y = S
10, X = S, Y = O;
11, X = O, Y = S
10, 11 13,
18–21. +
R = COOEt (14,18); C(S)NH2 (15,19); CONHPh (16,20);
! 2-(* !+,( $
5+4 1H, ': 1,33 (3 H, CH3,.2, J = 6,8); 2,06 (3 ., CH3); 4,20 (2 ., ,.2), J = 6,8); 6,84 (1 H, Ph); 7,19–7,28 (4 H, Ph); 9,65 (1 H, , %: C 63,77; H 6,32; N 13,12. C11H14N2O2. ) ! 4-* (% !-1-* !-1H- ( $ !-3-
5+4 1H, ': 1,42 (3 H, CH3,.2, J = 7,2); 4,42 (2 H, CH2), J = 7,2); 7,40 (1 H, Ph, J = 7,6); 7,51 (2 H, Ph, J = 7,6); 7,98 (2 H, Ph, J = 7,6); 9,17 , %: C 63,27; H 4,84; N 11,02. C13H12N2O3. (% !-1-* !-1H- ( $ !-3-
5+4 1., ': 7,41 (1 ., Ph, J = 8,0); 7,53 (2 ., Ph, J = 8,0); 8,00 (2 ., Ph, J = 8,0); 9,14 (1 ., $ ! 4-[(1,3-R2-2,4,6- (
" ( +,( -5(2H)-
% !]-1-* !-1 - ( $ !-3-
& (6, 7).
4-[(2,4,6- (
" ( +,( -5(2H)-
! , )% !]-1-* !-
1 - ( $!-3- (# " ! (6).
(2 H, CH2)); 7,48 (1 H, Ph); 7,60 (2 H, Ph); 7,85 (2 H, Ph); 8,96 (1 H, 9,67 (1 H, CH=); 11,31 (1 ., NH); 11,37 (1 ., NH). ! ! 4-[(1,3-, % !-2,4,6- (
" ( +,( -5(2H)-
!]-1-* !-1 - ( $ !-3-
(2), 0,32 (2,0
5+4 1H, ': 1,41 (3 H, CH3,.2); 3,12 (6 ., 2CH3N); 4,41 (2 H, CH2)); 7,49 (1 H, Ph); 7,60 (2 H, Ph); 7,83 (2 H, Ph); 9,01 (1 H, , %: C 58,91; H 4,55; N 14,32. C19H18N4O5. ) 4-[(4(2)- " -2(4)-
" -1,3-
$ ! , -5- ! , )% !]-1-* !-1 -
(10, 11). ,
4-[(4- " -2-
" -1,3-
$ ! , -5- ! , )% !]-1-* !-1 - ( -
(10). * . = 235 °,.
4-[(2- " -4-
" -1,3-
$ ! , -5- ! , )% !]-1-* !-1 - ( -
(11). * . = 238 °,.
CH3,.2); 4,34 (2 H, CH2)); 7,41 (1 H, Ph); 7,52 (2 H, Ph); 7,92 (2 H, Ph); 8,01 ! 4-[(3-% !-5-
" -1-* !-1,5-, +,( -4 - ( $ !-4- ! , )% !]-1-
* !-1 - ( $ !-3-
(2), 0,7 (4,1
, %: C 68,17; H 4,82; N 13,55. C23H20N4O3. ) 18–21.
14–17 8
-3- " -3- " -1- ( !)-1-* !-1 - ( $!-3- (# -
(18). * . = 126–128 °, (
CH3,.2); 1,43 (3 H, CH3,.2); 4,34 (2 H, CH2)); 4,41 (2 H, CH2)); 7,47 (1 H, Ph); 7,58 (2 H, Ph); 7,89 (2 H, Ph); 8,86 (1 H, CH=); 9,14 (1 H, -3- " -1- ( !)-1-* !-1 - ( $!-3- (# -
(19). * . = 188–190 °, (
1,43 (3 H, CH3,.2, J = 7,2); 4,43 (2 H, CH2), J = 7,2); 7,11 (1 H, Ph, J = 7,6); 7,33 (2 H, Ph, J = 7,6); 7,47 (1 H, Ph, J = 7,6); 7,60 (2 H, Ph, J = 7,6); 7,70 (2 H, Ph, J = 7,6); 7,92 (2 H, Ph, J = 7,6); 8,75 (1 H, CH=); 9,15 (1 H, , %: C 67,21; H 4,63; N 14,05. C22H18N4O3. ) 4-(3- % -2--
" -1- ( !)-1-* !-1 - ( $ !-3-
(20). * . = 264–265 °, ( +60).
(3 H, CH3,.2, J = 7,2); 4,41 (2 H, CH2), J = 7,2); 7,46 (1 H, Ph, J = 7,6); 7,59 (2 H, Ph, J = 7,6); 7,89 (2 H, Ph, J = 7,6); 8,70 (1 H, CH=); 9,16 (1 H, -2-(4-* !-1,3- $!-2- !) !]-1-* !-1 - ( $!-3- (-
(21). * . = 196 °, ( +60).
CH3,.2, J = 7,2); 4,45 (2 H, CH2), J = 7,2); 7,36 (1 ., Ph); 7,45 (3 ., Ph); 7,60 (2 ., Ph); 7,93 (2 ., Ph); 8,01 (2 ., Ph); 8,12 (1 ., , %: C 66,84; H 4,03; N 12,86, S 7,42. C24H18N4O2S. ) $ 2-* !-2,6-, +,( -7H- ( $ ! [3,4-d]
2, 18–21 7
5+4 1.: 7,47 (1 ., Ph, J = 7,6); 7,58 (2 H, Ph, J = 7,6); 8,03 (2 ., Ph, J = 7,6); 8,26 c 1. Bebernitz G.R., Argentieri G., Battle B., Brennan C., Balkan B., Burkey B.F. et al. The Effect of 1.3-Diaryl-[1H]-pyrazole-4-acetamides on Glucose Utilization in ob/ob Mice // J. Med. Chem. 2001. Vol. 44. N 16. P. 2601–2611. 2. Abadi A.H., Eissa A.A.H., Hassan G.S. Synthesis of novel 1,3,4-trisubstituted pyrazole derivatives and their evaluation as antitumor and antiangiogenic agents // Chem. Pharm. 3. Lange J.H.M., van Stuivenberg H.H., Coolen H.K.A.C., Adolfs T.J.P. et al. Bioisosteric replacements of the pyrazole moiety of rimonabant: synthesis, biological properties, and molecular modeling investigations of thiazoles, triazoles, and imidazoles as potent and selective CB1 cannabinoid receptor antagonists // J. Med. Chem. 2005. Vol. 48. N 6. 4. Mallegol T., Gmouh S., Meziane M.A.A., Blanchard-Desce M., Mongin O. Practical and Efficient Synthesis of Tris(4-formylphenyl)amine, a Key Building Block in Materials Chemistry // Synthesis. 2005. N 11. 4. 1771–1774. 5. Caluwe P. Heteroannelations with o-aminoaldehydes // Tetrahedron. 1980. Vol. 36. 6. Denison S., Hilton S.T. A Convenient Synthesis of 2-Cyano-3-Substituted Indoles // Synlett. 2004. N 15. P 2806–2808.07.12.204 7. Kira M.A., Abdel-Raemann M.O., Gadalla K.Z. The Vilsmeier–Haack reaction.
III. Cyclization of hydrazones to hyrazoles // Tetrahedron Lett. 1969. N 2. P. 109–110. 8. Kira M.A., Aboul-Enein N.M., Korkor K.Z. The Vilsmeier–Haack reaction. IV. Reaction
of Phosphorus Oxychloride-Dimethylformamide with Semicarbazones // J. Heterocycl. 9. Brehme R., Gründemann E., Schneider M. Reaktion von Acetophenonmono-methyl- und -dimethylhydrazonen mit dem Vilsmeier–Reagenz; Bildung von Pyrazol-4-
carbiminiumsalzen: ein Beitrag zum Mechanismus // J. Prakt. Chem. 2000. Bd. 7. SYNTHESIS AND CHEMICALS CHARACTERISTICS OF ETHYL
4-FORMYL-1-PHENYL-1H-PYRAZOLE-3-CARBOXYLATE
M. Potopnyk, V. Matiychuk
Ivan Franko National University of Lviv, Kyryla & Mefodiya Str., 6, 79005 Lviv, Ukraine Ethyl 4-formyl-1-phenyl-1H-pyrazole-3-carboxylate was synthesized by reaction of ethyl 2-(phenylhydrazono)propanoate with the Vilsmeier–Haack complex. New methods of synthesis of 2-phenil-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-one were suggested. Key words: pyrazoles, Vilsmeier–Haack reagent.

Source: http://chem.lnu.edu.ua/visnyk_2008/ORGAN/16_Potopnyk.pdf