Reduction of diketones I with zinc and formic acid gives monoketones II. Diketones Ia, IIIb, IIIc are converted with hydrazines to pyrazoles VIa, IVa, IVb, V. Methiodides VII are reduced with sodium borohydride to derivatives of 1-methyl-3-piperideine VIII-X.

This study extends the use of two lathyrogens, ss-aminopropionitrile (BAPN) and D-penicillamine (DPA) from daily systemic or local-topical administration to long-time acting agents. This was achieved by converting the hydrophilic drugs into lipophilic derivatives. The synthesis of functional derivatives of DPA consisted in esterification with methyl-, hexyl-, or benzyl alcohols in the presence of thionylchloride. The esters formed were hydrochlorides, acidic and soluble in water. During neutralization in vitro or in vivo by tissue fluid, an oily substance is formed that elutes from a hydrogel polymer at a much slower rate than hydroplilic DPA itself. The degree of lipophilicity, measured as a partition coefficient between octanol/water, was highest for hexyl ester and lowest for methyl ester DPA. A single injection of either DPA hexyl ester HCl or 3-hexyl(amino) propionitrile into the full thickness skin incision wound in rats significantly lowered the breaking strength of the wound 12 days after injection, indicating the interference with collagen cross-linking. Both agents injected into the breast adenocarcinoma in Fisher rats significantly inhibited tumor growth without any signs of local or systemic toxicity. We conclude that these lipophilic lathyrogens with prolonged effectiveness are suitable in the treatment of pathologies, consisting of excessively cross-linked or deposited collagen (fibrotic adhesions, strictures, stenosis, and scar contractures) and in the treatment of single, solitary tumors, malignant and benign.

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Using the reactions of 2,4- and 2,6-dimethylpyridine-1-oxides with aromatic and heteroaromatic aldehydes under catalysis with potassium tert-butoxide (E)-aryl- and (E)-heteroarylethenylpyridine-1-oxides IIIa-IIIe, IVa-IVc, Va, Vb respectively, were prepared. 1-Oxides IIIg, IVd, IVe and Vc were obtained from the appropriate pyridine bases by oxidation with peracetic acid. Condensation of 2,4- and 2,6-dimethylpyridines with 3-pyridinecarbaldehyde gives a mixture of bases VIa and VIc, and VIb and VId, respectively. On Claisen condensation of 2,6- or 2,4-dimethylpyridine-1-oxide with diethyl oxalate in the presence of sodium hydride and potassium tert-butoxide lactone XIIa and XIIb is formed in addition to α-keto ester XIa and XIb, respectively. From esters XIa and XIb amides XId and XIe were prepared.