Azole. 47. Uber 3-thiomorpholino- und 3-(4-methylpiperazino)-5-nitroindazole.

The structures of 5-nitro-3-thiomorpholino-1H-indazole, C(11)H(12)N(4)O(2)S, (IIa), and 3-(4-methylpiperazino)-5-nitro-1H-indazole-methanol-water (2/1/1), 2C(12)H(15)N(5)O(2).CH(3)OH.H(2)O, (IIIa), are described. In the crystal lattice of (IIa), the molecules are linked into dimers by N-H...N hydrogen bonds. The asymmetric unit of (IIIa) contains two independent molecules of the indazole moiety, one molecule of methanol and one of water. The three components of (IIIa) are linked by hydrogen bonds to form double chains running along the x axis. pi-Stacking involving the indazole moieties occurs in both compounds.

[Azole. 45(1). Uber 2,4-Dinitrophenylhydrazone von Morpholinonitroimidazolderivaten].

The three title compounds, namely (Z)-1-(4,5-dinitroimidazol-1-yl)-3-morpholinopropan-2-one 2,4-dinitrophenylhydrazone, C(16)H(17)N(9)O(9), (IV), (Z)-3-morpholino-1-(4-morpholino-5-nitroimidazol-1-yl)propan-2-one 2,4-dinitrophenylhydrazone, C(20)H(25)N(9)O(8), (Va), and (E)-3-morpholino-1-(4-morpholino-5-nitroimidazol-1-yl)propan-2-one 2,4-dinitrophenylhydrazone tetrahydrofuran solvate, C(20)H(25)N(9)O(8).C(4)H(8)O, (Vb), have been prepared and their structures determined. In (IV), the C-4 nitro group is nearly perpendicular to the imidazole ring and the C-4-NO(2) bond length is comparable to the value for a normal single Csp(2)-NO(2) bond. In (IV), (Va) and (Vb), the C-5 nitro group deviates insignificantly from the imidazole plane and the C-5-NO(2) bond length is far shorter in all three compounds than C-4-NO(2) in (IV). In consequence, the C-4 nitro group in (IV) is easily replaced by morpholine, while the C-5 nitro group in (IV), (Va) and (Vb) shows an extraordinary stability on treatment with the amine. The E configuration in (Vb) is stabilized by a three-centre hydrogen bond.

Azole. 44. Uber morpholinonitroimidazolderivate

The structure analyses of racemic 3-chloro-1-(4-morpholino-5-nitroimidazol-1-yl)propan-2-ol, C(10)H(15)ClN(4)O(4), (II), and 3-chloro-1-(5-morpholino-4-nitroimidazol-1-yl)propan-2-ol, C(10)H(15)ClN(4)O(4), (III), have been undertaken in order to determine the position of the morpholine residue in these two isomers. The morpholine residue in (II) is connected at the 4-position, while in (III), it is connected at the 5-position of the imidazole ring. The morpholine mean planes and nitro groups in the two compounds deviate from the imidazole planes to different extents. The nitro groups in (II) and (III) take part in the conjugation system of the imidazole rings. In consequence, the exocyclic C-N bonds are significantly shorter than the normal single Csp(2)-NO(2) bond and the nitro groups in (II) and (III) show an extraordinary stability on treatment with morpholine and piperidine [Gzella, Wrzeciono & Poppel (1999). Acta Cryst. C55, 1562-1565]. In the crystal lattice, the molecules of both compounds are linked by O-H.N and C-H.O intermolecular hydrogen bonds.

[Synthesis and anti-inflammatory activity of some indazole derivatives. 36. Azoles]. / Synthese und antiphlogistische Aktivität einiger Indazolderivate. 36. Mitteilung: Azole.

The synthesis of water soluble hydrochlorides of indazole derivatives 1b, 8 and 9 is described. By treating of 2,5-dinitroindazole with thiomorpholine 3-thiomorpholino-5-nitroindazole (10) and 3,5-dinitroindazole (11) in the form of the molecular compound 11a are obtained. The known indazole derivatives 1 and 7 as well as the newly synthesized hydrochlorides of 1b, 8 and 9 are, except of 8.HCl, less toxic than benzydamine hydrochloric (BZD). The same compounds show with some excepts a comparable or greater antiinflammatory effect than BZD in the carrageenin induced oedema test.

[Azoles. 34. Nitroimidazole derivatives and their antibacterial and fungicidal action]. / Azole. 34. Mitteilung4: Uber Nitroimidazolderivate und ihre antibakterielle und fungizide Wirkung.

Nitroimidazole derivatives 4a-4c, 5a-5c, 8a-8c and 9a-9c were synthesized by treating 4,5-dinitro- and 2-methyl-4,5-dinitroimidazole (1,2) or their silver salts [1.Ag,, 2.Ag) with chlorosubtituted phenacyl bromides 3a-3c, diethyl sulphate or ethyl iodide, allyl iodide and ethyl chloro-, azo- or bromoacetate. 2,4(5)-dinitroimidazole (10) has been converted to the 2,4-dinitroimidazole derivative 10a by the action of ethyl bromoacetate in the presence of sodium ethylate. A modified method for the synthesis of 6a and 6b has been described. 7a and 7b have been obtained by a known method. Some of the newly synthesized nitroimidazole derivatives show antibacterial and fungicidal activity.

[Azoles. 27. Nitroimidazole derivatives, their antibacterial and fungicidal activity and electron affinity]. / Azole. 27. Mitteilung5: Uber Nitroimidazolderivate, ihre antibakterielle und fungizide Wirkung und Elektronen-affinität.

Nitroimidazole derivatives 3a-3g, 4a-4g and 5-8 were synthesized by treating 4,5-dinitro- and 2-methyl-4,5-dinitroimidazole (1,2) with phenacyl bromide, its p-substituted derivatives or epichlorohydrin. 1-(3-Chloro-2-hydroxypropyl)-4,5-dinitroimidazole (5) and its 2-methyl derivative 6 have been converted to imidazo-oxazoles 7 and 8 or amino imidazole derivatives 9-14 by the action of potassium carbonate or cyclic amines (pyrrolidine, piperidine, morpholine and N-methylpiperazine). Some of the newly synthesized nitroimidazole derivatives show antibacterial and fungicidal activity. The electron affinity of the nitroimidazole derivatives 1-24 is discussed on the basis of their half-wave potentials and in the connection with their eventual radiosensitizing properties.

[Azoles. 18. Sulfonylindazole derivatives]. / Azole. 18. Mitteilung: Sulfonylindazolderivate.

The nucleophilic substitution of hydrogen to synthesize the sulphonyl indazole derivatives 9-16 is described. The structures of the substitution products are discussed using H-NMR spectra. Chemical structural proof was given by steric hindrance observed in the process of chorination of 9-16. The compounds 3, 4, 7, 8, 14, and 16 are studied to find an inhibition on phospholipase-A2 and lipoxygenase-I.

[Azoles. 17. Beta-(4-pyrazol)acrylic and propionic acids and their anti-inflammatory activity]. / Azole. 17. Mitteilung1: Beta-(4-Pyrazol)acryl- bzw. -propionsäure und ihre antiphlogistische Wirkung.

beta-(4-Pyrazole)acrylic acids 22-28 were prepared by the Knoevenagel reaction of malonic acid and 4-formylpyrazoles 8-14. 4-Pyrazolemethylenemalonic acids 15-21 were isolated as intermediates. The latter compounds were also synthesized by treating the 4-formylpyrazoles 8-14 with diethyl malonate followed by hydrolysis of the obtained diethyl esters 15a-21a. The effect of piperidine and pyridine on the Knoevenagel condensation was investigated. The beta-(4-pyrazole)acrylic acids 22-27, on catalytic reduction, gave the corresponding beta-(4-pyrazole)propionic acids 29-34. Compounds 23, 24, 27, 29-31 and 34 appeared to be less active than phenylbutazone in carrageenin-induced oedema test, but they were less toxic than the reference drug.

[Nitrogenous triterpene derivatives. 10. Hemisuccinates of some oleanolic acid derivatives and their antiulcer effect]. / Stickstoffhaltige Triterpenderivate. 10. Mitteilung: Hemisuccinate einiger Oleanolsäurederivate und deren Antiulkuswirkung.

The synthesis of hemisuccinates of some derivatives of oleanolic acid is reported, their inhibitory response to experimentally induced gastric ulcers in rats is examined. The hemisuccinates 13a (sodium salt of 13), 14 and 17 are more effective inhibitors than carbenoxolon-sodium.

[Nitrogenous triterpene derivatives. 9. 3-Acetyloleanol acid-28-amides and their antiulcer effect]. / Stickstoffhaltige Triterpenderivate. 9. Mitteilung: 3-Acetyloleanolsäure-28-amide und ihre antiulceröse Wirkung.

The authors report on the synthesis of 3-acetyloleanol acid-28-amids 10, 12-16, 19, 20, 22 and 24. The amids 16 (30%) and 24 (37%) were of most favourable inhibiting effect on the formation of gastric ulcera following pylorus ligature. The ulcer formation caused by p. o. administration of indometacin (Metindol) was in the main reduced by the amids 15 (60%), 16 (34%), and 24 (46%). With both the methods the effect of carbenoxolon sodium amounts to 40 or 50%. In ulcera induced by indometacin, the 11- and 3-oxooleanol acid derivates 12 and 18 revealed stimulating characteristics.

[Azoles. 12. Pyrazole carbolic acid thioamides]. / Azole. 12. Mitteilung: Pyrazolcarbonsäurethioamide.

Morpholids, N-methylpiperazids, piperidids and pyrrolidids of 5-methyl, 3,5-dimethyl-1-phenyl-4-pyrazolthioacetic acid and 3,5-dimethyl-1-phenyl-4-pyrazolcarbonic acid 4-12 are obtained by the Willgerodt-Kindler procedure. The oxothioamids 13-19 result as the intermediate products of the synthesis of thioamids 4-10. The compounds 4, 5, 8, 9, 11, 14 and 17 do not respond to Mycobacterium tuberculosis H37Rv. The thioamids 4, 8 and 11 are of slight toxicity (LD50 greater than 2.8 g/kg, albino-Swiss mice) and inhibit the Carrageenin oedema of the Wistar rat claw minor than phyenylbutazon and indometacin.

[Azoles. Part 5: On halogen-nitroindazole derivatives and their antibacterial properties (author's transl)]. / Azole. 5. Mitteilung: Uber Halogennitroindazolderivate und ihre antibakteriellen Eigenschaften.

The authors describe a modified procedure for the synthesis of the 3-halogenindazole derivatives 1--7 and of the 1-hydroxymethylindazole derivatives 8--14. The compounds 8--13 yield the corresponding 1-chloromethyl derivatives 15--20, and 23 is obtained from 3. The compounds 7--23 exert slight antibacterial effects.