10-Hydroxy-10-methyl-10,11-dihydroquinine, C21H28N2O3, a new derivative of quinine

Suszko-Purzycka, A.; Lipińska, Teodozja; Piotrowska, E.; Oleksyn, Barbara J.

doi:10.1107/s0108270185006254

Cited by 9 publications

(13 citation statements)

References 1 publication

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“…The bond lengths and angles in the bicyclic quinuclidine part of the molecule agree well with those observed in other Cinchona alkaloids such as derivatives of quinine and quinidine (Suszko-Purzycka et al, 1985;Suszko-Purzycka, Lipifiska, Karczmarzyk & Pniewska, 1987;Dupont et al, 1985), quinidine (Kashino & Haisa, 1983), cinchonidine (Oleksyn, 1982) and cinchonine (Oleksyn et al, 1979). However, the asymmetry of the N(1) -C(8) (41) 0.8022 (6) 0.500 0.500 11.4 (2) C (42) 0.7300 (5) 0.5122 (2) 0.5459 (2) 11.7 (1) C (43) 0.6025 (4) 0.5115 (2) 0.5447 (1) 7.9 (1) C (44) 0.5399 (5) 0.500 0.500 7.0 (1) C (45) 0.3935 (7) 0.500 0.500 14.1 (3) C (6) …”

Section: Meosupporting

confidence: 73%

“…The bond lengths and angles in the quinoline part of the molecule are in good agreement with corresponding values in other alkaloids containing the methoxyquinoline ring such as derivatives of quinine and quinidine (Suszko-Purzycka et al, 1985;Suszko-Purzycka et al, 1987;Dupont et al, 1985), and quinidine base (Kashino & Haisa, 1983). The only exception is the C(26)-C(27) bond length of 1.356 (4) A, which is somewhat short when compared with the average value of 1.410 (6) rings in the crystal.…”

Section: Meosupporting

confidence: 68%

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Structure of quinine monohydrate toluene solvate

Pniewska¹,

Suszko-Purzycka²

1989

Acta Crystallogr C

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Section: Meosupporting

confidence: 73%

Section: Meosupporting

confidence: 68%

Structure of quinine monohydrate toluene solvate

Pniewska¹,

Suszko-Purzycka²

1989

Acta Crystallogr C

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“…In neighboring molecules are nearly parallel to each other, with Fig. 4 the crystal structures of quinine (19), quinidine (7), their least-squares planes having an obliquity of 100 off and epiquinidine (1) are compared with each other. The parallel.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…Structural requirements include the presence of an aromatic portion and an amino alcohol portion such that the amine group and the alcohol group are separated by one or two carbon atoms (20). Of primary importance is considered to be the intramolecular N-O distance, which was estimated by model building with hand-held models to be optimally 3.0 A (1 A = 0.1 nm) (2) and which is 2.84 to 3.17 A in the crystalline form of the active cinchona alkaloids (7,10,12,13,19).The crystalline structure of enpiroline was determined to compare the following three-dimensional features of enpiroline with the cinchona alkaloids and WR 194,965: the aliphatic N-O distance, the orientation of the aliphatic N and 0 atoms, the direction of potential hydrogen bonding with receptor sites, the orientation of the aromatic rings, and the three-dimensional space occupied by enpiroline. …”

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confidence: 99%

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Crystal and molecular structure of the antimalarial agent enpiroline

Karle

1989

Antimicrob Agents Chemother

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To identify common spatial and structural features of amino alcohol antimalarial agents with the eventual goal of designing more effective drugs and a better understanding of the mechanism of action of this class of antimalarial agents, the three-dimensional crystal and molecular structure of enpiroline, a new antimalarial agent active against chloroquine-resistant Plasmodium falciparum, was determined by X-ray crystallography and compared with the crystal structures of the cinchona alkaloids and of the new antimalarial agent WR 194,965. The aromatic rings of the phenyl-pyridine ring system of enpiroline are twisted from each other by approximately 180. The intramolecular aliphatic N-O distance in enpiroline was 2.80 A (1 A = 0.1 nm), which is close to the N-O distance found in the antimalarial cinchona alkaloids. Enpiroline contains both an intramolecular hydrogen bond between the aliphatic nitrogen and oxygen atoms and an intermolecular hydrogen bond between the aliphatic nitrogen and oxygen atoms of two neighboring molecules. One enantiomer of enpiroline superimposed best with quinine, and the other enantiomer of enpiroline superimposed best with quinidine, suggesting that both enantiomers of enpiroline possess antimalarial activity. Since a common feature of the crystal structures of the amino alcohol antimalarial agents is the formation of intermolecular hydrogen bonds, the common spatial direction of hydrogen bond formation indicates the potential ability of these antimalarial agents to bind to a common receptor site. The crystallographic 1.46 g cm-3; source of radiation, CuKa (X = 1.54178 A); ,i (absorption coefficient) = 11.49 cm-'; F(000) (sum of atomic scattering factors at zero scattering angle) = 832; room temperature; final R = 8.7% for 1,798 reflections with FOI > 3of.With the continuing spread of multidrug-resistant Plasmodium falciparum malaria (14), the development of new antimalarial drugs is imperative. Enpiroline (Fig. 1, com falciparum infections (3).A detailed knowledge of the three-dimensional spatial requirements of the amino alcohol antimalarial agents should expedite the continued development of antimalarial drugs active against P. falciparum and provide clues to the mechanism of action of this class of antimalarial agents. The mechanism of action of quinoline-containing or amino alcohol or both antimalarial agents remains unknown (5,6,16). Alkalinization by antimalarial agents of parasite acid vesicles (11) appears to contribute to parasite toxicity, but does not provide a complete explanation of antimalarial activity due to the lack of direct correlation of pKas of the antimalarial * Corresponding author. agents with antimalarial activity and the unpredictability of the cross resistance of different parasite strains (4,5,16).Although the mechanism of antimalarial action of the amino alcohol antimalarial agents has not been determined, the activity of the amino alcohol antimalarial agents does have structural requirements, as exemplified by the active erythro cinchona alkaloids (quini...

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