Potential Antimalarials. XVIII. Some Mono- and Di-Mannich Bases of 3-[7-Chloro(and trifluoromethyl)quinolin-4-ylamino]phenol

1993 ◽  
Vol 46 (11) ◽  
pp. 1685 ◽  
Author(s):  
GB Barlin ◽  
SJ Ireland ◽  
TMT Nguyen ◽  
B Kotecka ◽  
KH Rieckmann
Keyword(s):  
Plasmodium Falciparum ◽  
Mannich Reaction ◽  
Mannich Base ◽  
Antimalarial Activity ◽  
Mannich Bases ◽  
Derivatives Of

Syntheses are reported for mono- and di-Mannich base derivatives of 3-[7-chloro(and trifluoro-methyl)quinolin-4-ylamino]phenols by Mannich reaction on 3-[7-chloro(and trifluoromethyl )-quinolin-4-ylamino]phenols or by condensation of Mannich base derivatives of 3-aminophenol, prepared from 3-nitrophenol, with the appropriate 4-chloroquinoline. The antimalarial activity of 3-(7′-chloroquinolin-4′-ylamino)-2,6-bis[ pyrrolidin-1″-ylmethyl -(or piperidin-1″-ylmethyl)]phenol against the FC-27 isolate of Plasmodium falciparum was comparable to that of chloroquine, and it was not significantly diminished in tests against the chloroquine -resistant K-1 isolate.

Potential Antimalarials. XVII. Di- and Mono-Mannich Bases of 2(and 4)-[2(and 8)-Trifluoromethylquinolin-4-ylamino]phenol

1993 ◽  
Vol 46 (1) ◽  
pp. 21 ◽  
Author(s):  
GB Barlin ◽  
TMT Nguyen ◽  
B Kotecka ◽  
KH Rieckmann
Keyword(s):  
Plasmodium Falciparum ◽  
Mannich Base ◽  
Antimalarial Activity ◽  
Mannich Bases ◽  
Sensitive Strain ◽  
In Vitro Tests ◽  
Derivatives Of

Di- and mono-Mannich base derivatives of 2(and 4)-[2(and 8)-trifluoromethylquinolin-4-ylamino]phenols have been prepared for comparison with the 7-trifluoromethyl isomers in tests for antimalarial activity. The order of activity in in vitro tests against the FC-27 ( chloroquine -sensitive) strain of Plasmodium falciparum was 7-CF3 >> 8-CF3 > 2-CF3.

Potential Antimalarials. XV. Di-Mannich Bases of 2-(7'-Chloroquinolin-4'-ylamino)phenol and 2-[7'-Bromo( and trifluoromethyl)-1',5'-naphthyridin-4'-ylamino]phenol

1992 ◽  
Vol 45 (10) ◽  
pp. 1651 ◽  
Author(s):  
GB Barlin ◽  
TMT Nguyen ◽  
B Kotecka ◽  
KH Rieckmann
Keyword(s):  
Mannich Base ◽  
Antimalarial Activity ◽  
Mannich Bases ◽  
In Vitro Tests ◽  
In Vivo Tests ◽  
Methyl Derivatives ◽  
Derivatives Of ◽  
Plasmodium Vinckei

A total of 26 di-Mannich base derivatives of 2-(7'-chloroquinolin-4'-ylamino)phenol and 2-[7'- bromo (and trifluoromethyl )-1',5'-naphthyridin-4'-ylino]phenol, such as 2-(7'-chloroquinolin- 4'-ylamino)-4,6-bis( piperidin-1″-ylmethyl )phenol, together with some 3- and 5-methyl derivatives and mono-Mannich analogues, have been prepared by condensation of the 4-chloro heterocycle with the appropriate Mannich base derivatives of 2-aminophenols. In in vitro tests against Plasmodium falciparum, many of the di-Mannich base derivatives of 2-(7'-chloroquinolin-4'-ylarnino)phenol exhibited activity comparable to or superior to chloroquine against the chloroquine -sensitive (FCQ-27) isolate, and vastly superior activity compared with chloroquine against the chloroquine -resistant (K-1) isolate. Strong antimalarial activity was also revealed in in vivo tests against Plasmodium vinckei vinckei in mice.

Potential Antimalarials. XXI. Mannich Base Derivatives of 4-[7-Chloro(and 7-trifluoromethyl)quinolin-4-ylamino]phenols

1994 ◽  
Vol 47 (8) ◽  
pp. 1553 ◽  
Author(s):  
GB Barlin ◽  
SJ Ireland ◽  
TMT Nguyen ◽  
B Kotecka ◽  
KH Rieckmann
Keyword(s):  
Plasmodium Falciparum ◽  
Mannich Base ◽  
Antimalarial Activity ◽  
Derivatives Of

Syntheses are reported for 4-(7-chloroquinolin-4-ylamino)-2,6-bis(piperidin-1-ylmethyl)phenol (2) and its 3-fluoro and 3-piperidinyl derivatives. Some mono-Mannich analogues with 2-fluoro, 2-t-butyl and 3-trifluoromethyl substituents have also been prepared. In tests for antimalarial activity against the FC-27 and K-1 isolates of Plasmodium falciparum in vitro, compound (2) proved to be the most active (IC50 6.3-12.5 nM).

Potential Antimalarials. XVI. 4'-Chloro-3-[7″-chloro(and trifluoromethyl)quinolin-4″-yl]amino-5-(substituted amino)methylbiphenyl-4-ols and 4'-Bromo(and 3'-trifluoromethyl)-3-(substituted amino)methyl-5-(7″-trifluoromethylquinolin-4″-yl)aminobiphenyl-2-ols

1992 ◽  
Vol 45 (11) ◽  
pp. 1845 ◽  
Author(s):  
GB Barlin ◽  
FL Tian ◽  
B Kotecka ◽  
KH Rieckmann
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Mannich Bases ◽  
In Vitro Tests ◽  
Ic50 Values

Twenty-four mono-Mannich bases of the general formulae 4'-chloro-3-[7″-chloro(and trifluoro-methyl)quinolin-4'-yl]amino-5-(substituted amino)methylbiphenyl-4-ols and 4'-bromo(and 3'- trifluoromethyl-3(substituted amino)methyl-5(7″-trifluoromethylquinolin-4″-yl) aminobiphenyl-2-ols have been prepared by condensation of the 4-chloro heterocycle with 5-amino-3-(N-substituted amino)methyl-4'-chlorobiphenyl-4-ols or 5-amino-3-(N-substituted amino)methyl- 4'-bromo(or 3'-trifluoromethyl)biphenyl-2-ols. The antimalarial activity of these products in in vitro tests against Plasmodium falciparum reveals many with IC50 values of 50-100 nM ( chloroquine 20-40 nM ). The biphenyl-2-ols were more active than comparable biphenyl-4-ols.

Potential Antimalarials. IX. Di-mannich Bases of 4-(7′-trifluoro-methylquinazolin-4′-ylamino)phenol and 4-(7′-Trifluoromethylquinolin-4′-ylamino)phenol

1990 ◽  
Vol 43 (2) ◽  
pp. 311 ◽  
Author(s):  
GB Barlin ◽  
C Jiravinyu
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Mannich Bases

Syntheses are reported for a series of di-Mannich bases of 4-(7′-trifluoromethylquinazolin-4′-ylamino)phenol derived from 4-chloro-7-trifluoromethylquinazoline with the di-Mannich bases of 4-aminophenol. Some analogous quinolines were prepared similarly. When tested for antimalarial activity against Plasmodium falciparum in vitro, the quinazolines were rather less active than the corresponding quinolines.

scholarly journals Two-Step Synthetic Approach to 6-Substituted Pyrido[2,3-d]pyrimidine(1H,3H)-2,4-diones from 6-Amino-, 6-Alkylamino-, and 6-Arylamino-1,3-dimethyluracils

2006 ◽  
Vol 61 (4) ◽  
pp. 486-494 ◽  
Author(s):  
Kerstin Bischoff ◽  
Ulrich Girreser ◽  
Dieter Heber ◽  
Martin Schütt
Keyword(s):  
Mannich Reaction ◽  
Mannich Base ◽  
Mannich Bases ◽  
Ring Closure ◽  
Synthetic Approach ◽  
Reaction Conditions ◽  
Iminium Salts ◽  
Vilsmeier Formylation ◽  
The Mannich Reaction

The Mannich reaction of 7-aryl-5,6-dihydropyrido[2,3-d]pyrimidines 3, easily accessible by condensation of 6-amino-1,3-dimethyluracil (1) with Mannich bases 2a - c, gives rise to a mixture of 7-aryl-6-(N,N-dimethylaminomethyl)pyrido[2,3-d]pyrimidines 6 and 7 as well as 1,2-bis- (7-arylpyrido[2,3-d]pyrimidin-6-yl)ethane 13 the ratio of which depends on the reaction conditions and the amine used. 6-Alkylamino-1,3-dimethyluracils 15 - 18 were converted to the corresponding 5-(3-oxo-3-phenylpropyl)uracils 19 - 22 by condensation with the Mannich base 2a. Ring closure of 19 - 22 was performed by Vilsmeier formylation to afford the 8-alkyl- and 7,8-diaryl-5,8- dihydropyrido[2,3-d]pyrimidine-6-carbaldehydes 9 - 12 via the corresponding iminium salts 27 - 30

scholarly journals Reaction of artemisinin with haemoglobin: implications for antimalarial activity

2005 ◽  
Vol 385 (2) ◽  
pp. 409-418 ◽  
Author(s):  
Rangiah KANNAN ◽  
Krishan KUMAR ◽  
Dinkar SAHAL ◽  
Shrikant KUKRETI ◽  
Virander S. CHAUHAN
Keyword(s):  
Ascorbic Acid ◽  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Competitive Inhibition ◽  
Antimalarial Activity ◽  
Food Vacuole ◽  
Primary Target ◽  
Reducing Environment ◽  
Derivatives Of ◽  
Antimalarial Action

Elucidation of the principal targets of the action of the antimalarial drug artemisinin is an ongoing pursuit that is important for understanding the action of this drug and for the development of more potent analogues. We have examined the chemical reaction of Hb with artemisinin. The protein-bound haem in Hb has been found to react with artemisinin much faster than is the case with free haem. It appears that the uptake of Hb and the accumulation of artemisinin into the food vacuole, together with the preferred reactivity of artemisinin with haem in Hb, may make Hb the primary target of artemisinin's antimalarial action. Both monoalkylated (HA) and dialkylated (HAA) haem derivatives of artemisinin have been isolated. These ‘haemarts’ bind to PfHRP II (Plasmodium falciparum histidine-rich protein II), inhibiting haemozoin formation, and possess a significantly decreased ability to oxidize ascorbic acid. The accelerated formation of HAA from Hb is expected to decrease the ratio of haem to its alkylated derivatives. The haemarts that are generated from ‘haemartoglobins’ may bring about the death of malaria parasite by a two-pronged effect of stalling the formation of haemozoin by the competitive inhibition of haem binding to its templates and creating a more reducing environment that is not conducive to the formation of haemozoin.

Potential Antimalarials. XII. 4-Chloro-3-(substituted amino)methyl-5-[7-bromo (and 7-trifluoromethyl)-1,5-naphthyridin-4-ylamino]biphenyl-2-ols and 4-Chloro-3-(substituted amino)methyl-5-(7-trifluoromethyl-quinazolin-4-ylamino)biphenyl-2-ols

1990 ◽  
Vol 43 (8) ◽  
pp. 1367 ◽  
Author(s):  
GB Barlin ◽  
C Jiravinyu
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Mannich Bases ◽  
Sensitive Isolate

The mono- Mannich bases 3-(t- butylamino )methyl-4?-chloro-, 3-(4- benzylpiperidin-1-yl)methyl-4′-chloro-, 3-(4-benzylpiperazin-1- yl )methyl-4′-chloro-, 4′-chloro-3-diethylaminomethyl-, 4′-chloro-3-(pyrrolidin-1-yl)methyl-, 4′-chloro-3-(piperidin-1-yl)methyl- and 4′-chloro-3-(3- and 4- methylpiperidin-1-yl)methyl-5-[7-bromo (and 7- trifluoromethyl )-1,5-naphthyridin-4-ylamino]- biphenyl-2-ol, and the corresponding substituted 5-(7-trifluoromethylquinazolin-4-ylamino)bi- phenyl-2-ols, have been prepared by condensation of the 5-amino-3-(N- substituted aminomethyl )-4′-chlorobiphenyl-2-ols and the appropriate 4-chloro heterocycle. The antimalarial activity of these products against the chloroquine-sensitive isolate (FCQ-27) of Plasmodium falciparum revealed that the 1,5-naphthyridines reported here were less active than the corresponding di-Mannich bases, e.g. (6), derived from 4-[7- bromo (and 7-trifluoromethyl)-1?,5′-naphthyridin-4′-ylamino]phenol, a feature not shared by the corresponding quinazolines.

Potential Antimalarials. XX. Mannich Base Derivatives of 2-[7-Chloroquinolin-4-ylamino and 7-Bromo(and 7-trifluoromethyl)-1,5-naphthyridin-4-ylamino]-4-chloro(or 4- or 6-t-Butyl or 4- or 5-fluoro)phenols and 4(or 6)-t-Butyl-2-(7-trifluoromethylquinolin-4-ylamino)phenol

1994 ◽  
Vol 47 (6) ◽  
pp. 1143 ◽  
Author(s):  
GB Bawrlin ◽  
SJ Ireland ◽  
TMT Nguyen ◽  
B Kotecka ◽  
KH Rieckmann
Keyword(s):  
Plasmodium Falciparum ◽  
Active Compound ◽  
Mannich Base ◽  
Derivatives Of

Syntheses are reported for some mono- and di-Mannich base derivatives of 4-chloro-, 3- or 4-fluoro-, or 2- or 4-t-butyl-substituted 2-(7′-chloroquinolin-4′-ylamino)phenols and 2-[7′-bromo(and 7′-trifluoromethyl)-1′,5′-naphthyridin-4′-ylamino]phenols. In tests against the FC-27 isolate of Plasmodium falciparum, the most active compound was 2-(7′-chloroquinolin-4′-ylamino)-5-fluoro-4,6-bis(piperidin-1′-ylmethyl)phenol (16) with IC50 12.2 nM.

Potential Antimalarials. XIII. Mono-Mannich Bases of 4-[7-Chloro (and 7-trifluoromethyl)quinolin-4-ylamino] and 4-(7-Bromo-1,5-naphthyridin-4-ylamino)-3-methylphenol

1991 ◽  
Vol 44 (1) ◽  
pp. 151 ◽  
Author(s):  
GB Barlin ◽  
C Jiravinyu
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Mannich Bases

The preparation of di-Mannich bases derived from 4-[7-chloro(and 7-trifluoromethyl)quinolin-4-ylamino] and 4-(7-bromo-1,5-naphthyridin-4-ylamino)-3-methylphenol are reported. In tests for antimalarial activity against the FCQ-27 ( chloroquine -sensitive) and K-1 ( chloroquine -resistant) isolates of Plasmodium falciparum in vitro, the 3-methylphenols were shown to be less active than their demethyl analogues reported previously.

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