A small library of phosphonopiperidylcarboxylic acids, analogues of NMDA antagonist selfotel (CGS 19755), was synthesized. First, the series of aromatic esters was obtained via a palladium-catalyzed cross-coupling reaction (Hirao coupling) of dialkyl phosphites with bromopyridinecarboxylates, followed by their hydrolysis. Then, hydrogenation of the resulting phosphonopyridylcarboxylic acids over PtO2 yielded the desired phosphonopiperidylcarboxylic acids. NMR studies indicated that the hydrogenation reaction proceeds predominantly by cis addition. Several compounds were obtained as monocrystal structures. Preliminary biological studies performed on cultures of neurons suggest that the obtained compounds possess promising activity toward NMDA receptors.

No abstract

The course of the reaction between phosphorus trichloride, acetamide and ethyl oxoalkanecarboxylates was studied in terms of the production of side-products. When ethyl 2-oxocycloalkane-and 4-oxocyclohexanecarboxylates were used as substrates, not only mixtures of the expected products-aminophosphonocycloalkanecarboxylic acids and their ethyl esters but AMIDOALKYLATION OF PHOSPHORUS TRICHLORIDE WITH ACETAMIDE 1069 substrate and solvent with phosphonylating agent) were observed. Ethyl 2-oxocyclooctanecarboxylate afforded the expected 2-amino-2-pohosphonocyclooctanecarboxylic acid in minute amounts. For comparison reactions of 1-butyloxocarbonyloxopiperidines afforded the desired aminopiperidinephosphonic acids in good yields and without formation of side-products.

Tinnitus from Historical PerspectiveThe origin of a name of a disorder derives from the Latin word "tinnire" that means "to ring" and in this context is defined as "ringing in the ear". Tinnitus-on the contrary to the common opinion-is the disorder known from the Antiquity. According to some authors [1], the first reference to tinnitus can be found in the Ebers Papyrus dated back to the 17 th Egyptian dynasty (1650-1532 B.C.) where it was defined as 'bewitched ear'. Tinnitus was not always treated as disease: ancient Indians recognized it as a sign of communion with space reserved only to spiritual elite; ancient Egyptians as a gift for divination; other civilizations considered it as Titus's curse-one of the most severe mythical punishments put on humanity [2]. The first undisputed reference to tinnitus was found in Corpus Hippocraticum where it was claimed that symptom is connected with hearing loss, headache and menstruation disorders. These annotations did not only concern the description of the disease but also methods of its treatment. Three methods were used: fumigation involving a variety of substances deriving from trees, herbs, sometimes even animal materials (bones or horns); insertion of wool treated with various materials into ears; direct administration of drugs to ear via a bronze tube [3]. Various materials such as honey, vinegar, rose oils, laurel oil etc. were applied. Galen (130-200 A.D.) used, as the first, sedatives like opium or mandrake juice in order to dull the brain's response to tinnitus. Therapy of tinnitus changed in the Renaissance when Paracelsus introduced first mineral-based drugs. Later, the more advanced techniques such as surgeries (beginning of 17 th century), electric stimulations (second half of 18 th century) or acoustic stimulation (middle of 19 th century) were developed. Characteristics of Tinnitus Definition and DescriptionTinnitus is defined as phantom auditory perception [4]. This broad definition includes the auditory hallucinations of schizophrenia, a variety of somatosounds such as palatal myoclonus, abnormal opening or patency of the Eustachian tube, temporomandibular joint disease, spontaneous otoacoustic emissions and sounds of vascular origin as well as sensation resulting from a malfunction of the cochlea or auditory nerve. Tinnitus can be classified as objective or subjective. Objective tinnitus can be heard by an observer and, what is more, it can be measured by means of appropriate equipment. Subjective tinnitus is heard only by the sufferer. Nowadays, objective tinnitus is treated as somatosounds.

Several analogues of the NMDA receptor antagonist selfotel are synthesized and tested for their biological activity.