Concentricol, a taxonomically significant triterpenoid from Daldinia concentrica.

In the course of a chemotaxonomic study of xylariaceous Ascomycetes, a major metabolite was isolated and identified from the ascostromata of Daldinia concentrica. The compound, for which the name concentricol is proposed, constitutes a highly oxidised squalene derivative. A survey of several Daldinia spp. from around the world (including several type materials), employing analytical HPLC-UV/Vis (with diode array detection) and positive electrospray HPLC-MS of stromatal MeOH extracts revealed that concentricol was omnipresent in the stromata of D. concentrica, as well as in those of several collections of the pantropical Daldinia eschscholzii. All other investigated Daldinia spp. were found devoid of concentricol but contained binaphthalenes, benzophenones and/or azaphilones as further taxonomically relevant main metabolites.

[2-(Guanidino)-anilides and related compounds. Synthesis and anthelmintic effect. 3. Anthelmintics]. / 2-(Guanidino)-anilide und verwandte Verbindungen. Synthese und anthelmintische Wirkung. 3. Mittelung: Anthelmintika.

Anilides bearing a guanidino, thioallophanato, isothioallophanato or amidino group in the ortho position were synthesised (6) for investigations of their anthelmintic effects, and tested against sheep trichostrongylides. The most active anilides are those containing a 5-alkylthio, 5-alkylsulphinyl (alkyl = C3H7, C4H9), 5-phenylthio, 5-phenylsulphinyl or 4-phenylsulphonyloxy group, and a guanidino group substituted at both nitrogen atoms by a methoxycarbonyl group. The most active anthelmintic anilides are the form-, propion-, butyr- and methoxy-acetanilides (e.g. 60, 61, 66, 95, 100, 110). Of the guanidines unsubstituted at N' and N", the 2-guanidino-5-phenylthio-2-methoxyacetanilide (123) and the 2-guanidino-5-phenylsulphinyl-2-methoxyacetanilide (152) were more active than parbendazole. From the class of bismethoxycarbonylguanidines (6 alpha), which are also the most interesting products in terms of stability, febantel (110, Rintal) has been introduced into veterinary practice for the treatment of nematode infections in horses, cattle, sheep and swine.

[3-Amino-2H-1,2,4-benzothiadiazine-1,1-dioxides with antihypertensive and possibly diabetogenic activity (author's transl)]. / 3-Amino-2H-1,2,4-benzothiadiazin-1,1-dioxide mit antihypertensiver und potentieller diabetogener Wirkung.

By reaction of dialkylaminoalkylamines or omega-amino-alkylethers with 2H-1,2,4-benzothiadiazine-1,1-dioxides bearing a group in the 3-position labile towards nucleophilic substitution (Cl, CH3S, CH3CO2), the corresponding 3-substituted amino-2H-1,2,4-benzothiadiazine-1,1-dioxides are obtained. A series of these compounds exerts an antihypertensive effect in the renally hypertonic rat after oral administration and in the "two-kidney hypertensive dog" after parenteral administration. Two compounds (1 and 4) were studied thoroughly in comparison to diazoxide (16) and the known piperazino compound (17). At 10 mg/kg in the rat, diazoxide causes a marked reduction of water and electrolyte excretion but at this dosage 1 and 4 are neither diuretic nor antidiuretic. In the hyperglycaemia test on normal rats at a dosage 30--100 times that required for an antihypertensive effect, 1 and 4 show after 300 mg/kg no hyperglycaemic effect and after 1000 mg/kg p.o. a very weak one. 17 has a weak hyperglycaemic effect at 300 mg/kg diazoxide a strong one. However, intensive glucose loading studies on diabetic rats (reduced glucose-tolerance) and on metabolically healthy rats with glucose loading showed that compounds 1 and 4 as well as the piperazine derivative 17 inhibit insulin release, albeit in higher doses than does diazoxide. In animals with insulin resistance a diabetic metabolic condition occurs with high blood-sugar levels. Owing to this possible diabetogenic activity, testing and application of 1, 4 and the known 7-chloro-3-(4-methyl-1-piperazinyl)-2H-1,2,4-benzothiadiazine-1,1-dioxide for blood-sugar lowering activity to human volunteers is not considered appropriate.

Amidantel, a potent anthelminthic from a new chemical class.

N-(4-[(1-(Dimethylamino)-ethylidene)-amino]-phenyl)-2 methoxyacetamide hydrochloride (amidantel, BAY d 8815) is a new aminophenylamidine with an interesting anthelminthic spectrum. In rodents the compound is active against nematodes, filariae and cestodes. Of special interest is the high efficacy in dogs against hookworms and large roundworms. Amidantel was well tolerated by all animals tested and did not show teratogenic effects.

Febantel, a new broad-spectrum anthelminthic.

N-(2-[2,3-Bis-(methoxycarbonyl)-guanidino]-5-(phenylthio)-phenyl)-2-methoxyacetamide (febantel, Rintal) is a new compound which is highly active against various species of nematodes and cestodes in mice, rats, dogs, sheep and cattle. In sheep and cattle a single oral dose of 5 mg/kg resulted in an almost complete elimination of larval and adult intestinal nematodes as well as Dictyocaulus. The compound was well tolerated by all animals tested.