Compounds of this invention are non-peptide, reversible inhibitors of type 2 methionine aminopeptidase, useful in treating conditions mediated by angiogenesis, such as cancer, haemangioma, proliferative retinopathy, rheumatoid arthritis, atherosclerotic neovascularization, psoriasis, ocular neovascularization and obesity.

Compounds and methods

1,5-Diamino-1H-tetrazole (2, DAT) can easily be protonated by reaction with strong mineral acids, yielding the poorly investigated 1,5-diaminotetrazolium nitrate (2a) and perchlorate (2b). A new synthesis for 2 is introduced that avoids lead azide as a hazardous byproduct. The reaction of 1,5-diamino-1H-tetrazole with iodomethane (7a) followed by the metathesis of the iodide (7a) with silver nitrate (7b), silver dinitramide (7c), or silver azide (7d) leads to a new family of heterocyclic-based salts. In all cases, stable salts were obtained and fully characterized by vibrational (IR, Raman) spectroscopy, multinuclear NMR spectroscopy, mass spectrometry, elemental analysis, X-ray structure determination, and initial safety testing (impact and friction sensitivity). Most of the salts exhibit good thermal stabilities, and both the perchlorate (2b) and the dinitramide (7c) have melting points well below 100 degrees C, yet high decomposition onsets, defining them as new (7c), highly energetic ionic liquids. Preliminary sensitivity testing of the crystalline compounds indicates rather low impact sensitivities for all compounds, the highest being that of the perchlorate (2b) and the dinitramide (7c) with a value of 7 J. In contrast, the friction sensitivities of the perchlorate (2b, 60 N) and the dinitramide (7c, 24 N) are relatively high. The enthalpies of combustion (Delta(c)H degrees ) of 7b-d were determined experimentally using oxygen bomb calorimetry: Delta(c)H degrees (7b) = -2456 cal g(-)(1), Delta(c)H degrees (7c) = -2135 cal g(-)(1), and Delta(c)H degrees (7d) = -3594 cal g(-)(1). The standard enthalpies of formation (Delta(f)H degrees ) of 7b-d were obtained on the basis of quantum chemical computations using the G2 (G3) method: Delta(f)H degrees (7b) = 41.7 (41.2) kcal mol(-)(1), Delta(f)H degrees (7c) = 92.1 (91.1) kcal mol(-)(1), and Delta(f)H degrees (7d) = 161.6 (161.5) kcal mol(-)(1). The detonation velocities (D) and detonation pressures (P) of 2b and 7b-d were calculated using the empirical equations of Kamlet and Jacobs: D(2b) = 8383 m s(-)(1), P(2b) = 32.2 GPa; D(7b) = 7682 m s(-)(1), P(7b) = 23.4 GPa; D(7c) = 8827 m s(-)(1), P(7c) = 33.6 GPa; and D(7d) = 7405 m s(-)(1), P(7d) = 20.8 GPa. For all compounds, a structure determination by single-crystal X-ray diffraction was performed. 2a and 2b crystallize in the monoclinic space groups C2/c and P2(1)/n, respectively. The salts of 7 crystallize in the orthorhombic space groups Pna2(1) (7a, 7d) and Fdd2 (7b). The hydrogen-bonded ring motifs are discussed in the formalism of graph-set analysis of hydrogen-bond patterns and compared in the case of 2a, 2b, and 7b.

http://www.sciencemadness.org/talk/files.php?pid=217935&aid=15474

Derivatives of 1,5-diamino-1H-tetrazole: a new family of energetic heterocyclic-based salts.

Prototropic Tautomerism of Heterocycles: Heteroaromatic Tautomerism—General Overview and Methodology

these high-energy-density materials (HEDM). Surprisingly, substitution of the heterocyclic tetrazole ring with amino groups is one of the simplest methods to enhance thermal stability, even though 1 contains 84.0% nitrogen. Nearly 80 years ago 1 was prepared by treatment of thiosemicarbazide with lead(II) oxide and sodium azide. In 1984, further investigation into its synthesis and properties gave 1 in 59% yield. Later, 1 was synthesized by using aminoguanidinium chloride and HNO2. [5] The reaction mixture was carefully brought to pH 8 with sodium carbonate in order to deprotonate the amino-substituted azido guanyl chloride intermediate, which cyclized to form 1 in 58% yield. However, a further report that appeared in the same year recommended special caution in the synthesis of 1. This stated that 1 was pure following ethanol extraction; however, during extraction by ethanol a very shock sensitive alkali metal salt of tetrazolyl azide often was observed as a byproduct, produced by double diazotization of diaminoguanidine with HNO2. In our continuing interest in the development of energetic materials, we have now synthesized derivatives of 1,5diaminotetrazole in situ by reaction of cyanogen azide with monosubstituted hydrazine derivatives (Scheme 2).

Energetic Nitrogen-Rich Derivatives of 1,5-Diaminotetrazole†

Data concerning the methods of synthesis, chemical transformations and application of levulinic acid are analysed and generalised. The wide synthetic potential of levulinic acid, particularly as a key compound in the synthesis of various heterocyclic systems, saturated and unsaturated ketones and diketones, difficultly accessible acids and other compounds is demonstrated. The accessibility of levulinic acid from hexose-containing wood-processing and agricultural wastes is noted. The bibliography includes 260 references.

https://iopscience.iop.org/article/10.1070/RC1999v068n01ABEH000381/pdf

Levulinic acid in organic synthesis

On triazoles XI . structure elucidation of isomeric 1,2,4-triazolopyrimidinones

On triazoles. I. The reaction of N‐cyanocarbonimidodithioic acid diesters with hydrazines

On triazoles. V. Synthesis of 1- and 2-R1-3-R2,R3-amino-5-amino-1,2,4-triazoles†‡

On Triazoles. VI. The acylation of 5-amino-1,2,4-triazoles

A 1H NMR and 13C NMR study of all possible isomers of monoalkylated 3-methylthio-5-amino-1,2,4-triazoles was carried out. The 13C NMR spectra, including the corresponding proton coupled measurements, proved unambiguously the structures of all derivatives studied.

Jozsef Reiter

Papers

On triazoles XI . structure elucidation of isomeric 1,2,4-triazolopyrimidinones

On triazoles. I. The reaction of N‐cyanocarbonimidodithioic acid diesters with hydrazines

On triazoles. V. Synthesis of 1- and 2-R1-3-R2,R3-amino-5-amino-1,2,4-triazoles†‡

On Triazoles. VI. The acylation of 5-amino-1,2,4-triazoles

On triazoles. IV—NMR study of 5‐amino‐1,2,4‐triazole isomers