RESUMEN
The acid-induced rearrangement of three epoxyderivatives of nobilin 1, the most abundant sesquiterpene lactone in Anthemisnobilis flowers, was investigated. From the 1,10-epoxyderivative 2, furanoheliangolide 5 was obtained, while the 4,5-epoxy group of 3 did not react. Conversely, when the 3-hydroxy function of nobilin was acetylated (12), the 4,5-epoxy derivative did cyclize into cadinanes (15 and 16) under Lewis acid catalysis. The reactivity of the 4,5- and 1,10-epoxy derivatives of nobilin (2 and 3) was compared with that of parthenolide, and rationalized on the basis of quantum chemical calculations. All isolated reaction products were fully characterized by spectroscopic and computational methods, and their in vitro anti-protozoal activity was evaluated. The paper could provide new insights into the biosynthesis of this class of natural products.
Asunto(s)
Hidrocarburos Aromáticos con Puentes/síntesis química , Chamaemelum/química , Furanos/síntesis química , Sesquiterpenos de Germacrano/química , Sesquiterpenos/síntesis química , Antiprotozoarios/síntesis química , Antiprotozoarios/química , Antiprotozoarios/farmacología , Hidrocarburos Aromáticos con Puentes/química , Hidrocarburos Aromáticos con Puentes/farmacología , Catálisis , Ciclización , Furanos/química , Furanos/farmacología , Concentración 50 Inhibidora , Leishmania donovani/efectos de los fármacos , Ácidos de Lewis/química , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Plasmodium falciparum/efectos de los fármacos , Sesquiterpenos Policíclicos , Sesquiterpenos/química , Sesquiterpenos/farmacología , Sesquiterpenos de Germacrano/aislamiento & purificación , Sesterterpenos , Trypanosoma brucei rhodesiense/efectos de los fármacos , Trypanosoma cruzi/efectos de los fármacosRESUMEN
There is a need for fast detection methods for the banned rodenticide tetramethylenedisulfotetramine (TETS), a highly potent blocker of the γ-aminobutyric acid (GABAA ) receptors. General synthetic approach toward two groups of analogues was developed. Screening of the resulting library of compounds by FLIPR or whole-cell voltage-clamp revealed that, despite the structural differences, some of the TETS analogues retained GABAA receptor inhibition; however, their potency was an order of magnitude lower. Antibodies raised in rabbits against some of the TETS analogues conjugated to protein recognized free TETS and will be used for the development of an immunoassay for TETS.
Asunto(s)
Hidrocarburos Aromáticos con Puentes/síntesis química , Haptenos/química , Receptores de GABA-A/metabolismo , Bibliotecas de Moléculas Pequeñas/síntesis química , Animales , Hidrocarburos Aromáticos con Puentes/farmacología , Evaluación Preclínica de Medicamentos/métodos , Fenómenos Electrofisiológicos/fisiología , Humanos , Inmunoensayo/métodos , Concentración 50 Inhibidora , Estructura Molecular , Neuronas , Conejos , Bibliotecas de Moléculas Pequeñas/farmacología , Relación Estructura-ActividadRESUMEN
Taxus canadensis distributed mainly in North America, such as northern Minnesota, Newfoundland, south to Wisconsin and Pennsylvania. Its composition has been shown to be very different from other species, and in recent years, some new skeletons also have been found in Canada yew. Through analysis of the taxanes content on various Taxus plants containing taxanes, the results showed a higher content of taxol in T. canadensis. Based on the current research on T. canadensis (from the research results of the author in recent years, as well as from studies of scholars in the field), the paper outlined the research progress in recent years on the chemical constituents of taxane of T. canadensis and the spectral characteristics of various types of compounds. Besides, this paper analyzed the present research about solutions for the taxol drug source crisis.
Asunto(s)
Hidrocarburos Aromáticos con Puentes/química , Extractos Vegetales/química , Plantas Medicinales/química , Taxoides/química , Taxus/química , Animales , Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/farmacología , Humanos , Estructura Molecular , Extractos Vegetales/síntesis química , Extractos Vegetales/farmacología , Taxoides/síntesis química , Taxoides/farmacologíaRESUMEN
The first broadly applicable set of protocols for efficient Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Cyclizations are performed with 1.2-7.5 mol% of a Mo- or W-based monoaryloxide pyrrolide (MAP) complex at 22 °C and proceed to complete conversion typically within two hours. Utility is demonstrated by synthesis of representative macrocyclic alkenes, such as natural products yuzu lactone (13-membered ring: 73% Z) epilachnene (15-membered ring: 91% Z), ambrettolide (17-membered ring: 91% Z), an advanced precursor to epothilones C and A (16-membered ring: up to 97% Z), and nakadomarin A (15-membered ring: up to 97% Z). We show that catalytic Z-selective cyclizations can be performed efficiently on gram-scale with complex molecule starting materials and catalysts that can be handled in air. We elucidate several critical principles of the catalytic protocol: 1) The complementary nature of the Mo catalysts, which deliver high activity but can be more prone towards engendering post-RCM stereoisomerization, versus W variants, which furnish lower activity but are less inclined to cause loss of kinetic Z selectivity. 2) Reaction time is critical to retaining kinetic Z selectivity not only with MAP species but with the widely used Mo bis(hexafluoro-tert-butoxide) complex as well. 3) Polycyclic structures can be accessed without significant isomerization at the existing Z alkenes within the molecule.
Asunto(s)
Alcaloides/síntesis química , Productos Biológicos/síntesis química , Hidrocarburos Aromáticos con Puentes/síntesis química , Carbolinas/síntesis química , Cicloparafinas/síntesis química , Epotilonas/síntesis química , Lactonas/síntesis química , Compuestos Macrocíclicos/síntesis química , Molibdeno/química , Rutenio/química , Alcaloides/química , Productos Biológicos/química , Hidrocarburos Aromáticos con Puentes/química , Carbolinas/química , Catálisis , Ciclización , Cicloparafinas/química , Epotilonas/química , Cinética , Lactonas/química , Compuestos Macrocíclicos/química , Estructura Molecular , EstereoisomerismoRESUMEN
An improved synthetic method for triplet drugs with the 1,3,5-trioxazatriquinane skeleton was developed that used p-toluenesulfonylmethyl isocyanide (TosMIC) instead of 1,3-dithiane. Using the improved method, we synthesized compounds with two identical pharmacophore units and an epoxymethano group, that is, capped homotriplets. Among the synthesized capped homotriplets, KNT-123 showed high selectivity for the µ receptor over the κ receptor, and the µ selectivity was the highest among the reported µ selective nonpeptide ligands. KNT-123 administered subcutaneously induced a dose-dependent analgesic effect in the acetic acid writhing assay, and its potency was 11-fold more potent than that of morphine. KNT-123 may serve as a useful tool for the study of the pharmacological actions mediated specifically via the µ receptor.
Asunto(s)
Analgésicos Opioides/química , Analgésicos Opioides/uso terapéutico , Hidrocarburos Aromáticos con Puentes/química , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Dolor Nociceptivo/tratamiento farmacológico , Receptores Opioides kappa/metabolismo , Receptores Opioides mu/metabolismo , Sesquiterpenos/química , Sesquiterpenos/uso terapéutico , Analgésicos Opioides/síntesis química , Analgésicos Opioides/farmacología , Animales , Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/farmacología , Ratones , Modelos Moleculares , Nitrilos/síntesis química , Nitrilos/química , Nitrilos/farmacología , Nitrilos/uso terapéutico , Nocicepción/efectos de los fármacos , Dimensión del Dolor/efectos de los fármacos , Sesquiterpenos/síntesis química , Sesquiterpenos/farmacología , Compuestos de Tosilo/síntesis química , Compuestos de Tosilo/química , Compuestos de Tosilo/farmacología , Compuestos de Tosilo/uso terapéuticoRESUMEN
1-Deoxy-9alpha-dihydrotaxane analogs 9 and 10 were semi-synthesized from 1-deoxybaccatin VI, isolated from Taxus mairei, and tested for cytotoxic activity. Taxane 9 is 10-fold less cytotoxic than paclitaxel, while 10 is equally active. In the tubulin polymerization assay (ED(50) values), 10 is 4-fold less effective than paclitaxel, but 3-fold superior to 9. These observations can be explained by analysis of the corresponding taxane/beta-tubulin complexes.
Asunto(s)
Hidrocarburos Aromáticos con Puentes , Taxoides , Moduladores de Tubulina , Tubulina (Proteína)/efectos de los fármacos , Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Plantas Medicinales/química , Estereoisomerismo , Taxoides/síntesis química , Taxoides/farmacología , Taxus/química , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologíaRESUMEN
Recently, we synthesized pyrimidine derivatives of the 2'-O,4'-C-methylenoxymethylene-bridged nucleic-acid (2',4'-BNA(COC)) monomer, the sugar conformation of which is restricted in N-type conformation by a seven-membered bridged structure. Oligonucleotides (BNA(COC)) containing this monomer show high affinity with complementary single-stranded RNA and significant resistance to nuclease degradation. Here, BNA(COC) consisting of 2',4'-BNA(COC) monomers bearing all four bases, namely thymine, 5-methylcytosine, adenine and guanine was efficiently synthesized and properties of duplexes containing the 2',4'-BNA(COC) monomers were investigated by UV melting experiments and circular dichroism (CD) spectroscopy. The UV melting curve analyses showed that the BNA(COC)/BNA(COC) duplex possessed excellent thermal stability and that the BNA(COC) increased thermal stability with a complementary RNA strand. On the other hand, BNA(COC)/DNA heteroduplexes showed almost the same thermal stability as RNA/DNA heteroduplexes. Furthermore, mismatched sequence studies showed that BNA(COC) generally improved the sequence selectivity with Watson-Crick base-pairing compared to the corresponding natural DNA and RNA. A CD spectroscopic analysis indicated that the BNA(COC) formed duplexes with complementary DNA and RNA in a manner similar to natural RNA.
Asunto(s)
Ácidos Nucleicos/química , Oligonucleótidos/química , ARN/química , 5-Metilcitosina/química , Adenina/química , Disparidad de Par Base , Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/química , Dicroismo Circular , ADN/química , Guanina/química , Conformación de Ácido Nucleico , Desnaturalización de Ácido Nucleico , Oligonucleótidos/síntesis química , Timina/químicaRESUMEN
The cytotoxicity against A172 human malignant glioma cells was examined for 14 alkaloids from the roots of Aconitum yesoense var. macroyesoense and of Aconitum japonicum and from the seeds of Delphinium elatum as well as for 25 semisynthetic derivatives. The major alkaloid constituents of A. yesoense var. macroyesoense, kobusine (2) and pseudokobusine (3), a minor alkaloid constituent of A. japonicum, aljesaconitine A (5), and six alkaloid derivatives, N-deethyldelcosine (10), N-deethyldelsoline (11), 12-benzoylluciculine (18), 12-anisoylluciculine (19), 6,11-dibenzoylpseudokobusine (28), and 6-veratroylpseudokobusine (29), had only very weak activity. Four acylated alkaloid derivatives, 12-acetylluciculine (23), 11-veratroylpseudokobusine (30), 11-(m-trifluoromethylbenzoyl)pseudokobusine (32), and 11-(m-trifluoromethylbenzoyl)kobusine (39), exhibited more potent activity, while pseudokobusine 11-cinnamoate (31), 11-anisoate (33), and 11-p-nitrobenzoate (34) were found to be the most potent cytotoxic agents.
Asunto(s)
Aconitum/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Plantas Medicinales/química , Alcaloides/química , Antineoplásicos Fitogénicos/química , Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/química , Hidrocarburos Aromáticos con Puentes/farmacología , Diterpenos/síntesis química , Diterpenos/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Raíces de Plantas/química , Compuestos Policíclicos/síntesis química , Compuestos Policíclicos/química , Compuestos Policíclicos/farmacología , Semillas/químicaRESUMEN
Bayer Corp, under license from Indena SpA, is developing BAY-59-8862, a taxane synthesized from 14beta-hydroxy-10-deacetylbaccatin III, for the potential treatment of cancer.
Asunto(s)
Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Hidrocarburos Aromáticos con Puentes/efectos adversos , Hidrocarburos Aromáticos con Puentes/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Taxoides/efectos adversos , Taxoides/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Antineoplásicos/toxicidad , Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/farmacocinética , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Hidrocarburos Aromáticos con Puentes/toxicidad , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Relación Estructura-Actividad , Taxoides/síntesis química , Taxoides/farmacocinética , Taxoides/uso terapéutico , Taxoides/toxicidadRESUMEN
In previous studies, the polycyclic cage amine 8-benzylamino-8,11-oxapentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane (NGP1-01) and a number of its derivatives showed positive effects in neuroprotection studies with MPTP, in vivo. In view of these findings, we examined these compounds for their effects on [(3)H]dopamine ([(3)H]DA) release and uptake inhibition in murine striatal synaptosomes, as well as for inhibition of baboon liver monoamine oxidase (MAO) B. In order to assess specificity, initial experiments focused on compounds that blocked dopamine uptake without causing appreciable release (<40% at 100 microM) of the transmitter. NGP1-01 blocked the uptake of [(3)H]DA with an IC(50) of 57 microM, while another compound, 8-phenylethyl-8,11-oxapentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane, blocked uptake at an IC(50) value of 23 microM. These values were comparable to that of another polycyclic cage amine, amantadine (IC(50); 82 micro), that is used in parkinsonian therapy. Structure-activity relationships of this series of compounds support the importance of geometric and steric, rather than electronic effects, in determining biological activity. MAO-B inhibition for this group was weak, with less than 50% inhibition at 300 microM for any of the compounds in the series. The present study suggests that blockage of the dopamine transporter may underlie, at least in part, their neuroprotective effects against MPTP-induced parkinsonism. These compounds may be considered as potential lead compounds for Parkinson's Disease therapy.
Asunto(s)
Antiparkinsonianos/síntesis química , Antiparkinsonianos/farmacología , Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/farmacología , Enfermedad de Parkinson/metabolismo , Animales , Antiparkinsonianos/farmacocinética , Hidrocarburos Aromáticos con Puentes/farmacocinética , Dopamina/química , Dopamina/metabolismo , Dopamina/farmacocinética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Masculino , Glicoproteínas de Membrana/efectos de los fármacos , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana/efectos de los fármacos , Proteínas de Transporte de Membrana/metabolismo , Ratones , Ratones Endogámicos ICR , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/enzimología , Mitocondrias Hepáticas/metabolismo , Modelos Moleculares , Estructura Molecular , Monoaminooxidasa/efectos de los fármacos , Monoaminooxidasa/metabolismo , Neostriado/química , Proteínas del Tejido Nervioso/efectos de los fármacos , Proteínas del Tejido Nervioso/metabolismo , Papio , Relación Estructura-Actividad , Sinaptosomas/química , Sinaptosomas/efectos de los fármacosRESUMEN
[structure: see text] Two cytotoxic quaternary Daphniphyllum alkaloids with an unprecedented fused-polycyclic skeleton containing a 1-azoniatetracyclo[5.2.2.0.(1,6)0.(4,9)]undecane ring system, daphniglaucins A (1) and B (2), have been isolated from the leaves of Daphniphyllum glaucescens. Their structures and relative stereochemistry were elucidated on the basis of spectroscopic data.
Asunto(s)
Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/aislamiento & purificación , Plantas Medicinales/química , Compuestos Policíclicos/síntesis química , Compuestos Policíclicos/aislamiento & purificación , Japón , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Conformación Molecular , Extractos Vegetales/química , Hojas de la Planta/química , Espectrometría de Masa Bombardeada por Átomos VelocesRESUMEN
Taxanes represent the most important class of antitumor agents introduced in cancer therapy in the last decade. The first member of the family was paclitaxel, firstly isolated from Taxus Brevifolia and found active as antitumor agent at the end of 60's. In the mid of 90's, a semi-synthetic taxane derived from 10-deacetylbaccatin III was introduced and thereafter named as docetaxel. Taxanes act by inhibiting microtubule dynamics, thereby inducing the arrest in M phase and the consequent activation of the apoptotic program. Since target of taxanes is not directly the genome, they are effective alone or in combination with DNA-damaging drugs in tumors not responding to conventional chemotherapeutics, such as advanced breast and non small cell lung cancer. In this review we will cover the aspects of clinical applications of the currently used taxanes as well as the clinical problems related to their use. Taking into consideration such problems, new taxanes have been developed in order to extend the spectrum of taxane-sensitive tumors and several of them are currently undergoing clinical trials. Among these agents, a newly developed taxane (BAY 59-8862) appears particularly interesting for the fact that it shows excellent oral bioavailability and activity in tumors with inherent resistance to paclitaxel.
Asunto(s)
Antineoplásicos/uso terapéutico , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Resistencia a Antineoplásicos , Neoplasias/tratamiento farmacológico , Taxoides , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/química , Ensayos Clínicos como Asunto , HumanosRESUMEN
The root bark of Tabernanthe iboga contains ibogaine as its predominant alkaloid and has been an important source of it. Ibogaine is used experimentally to interrupt drug addiction and allow therapeutic intervention, but is currently unaffordable to doctors in less economically developed countries. To meet this need, an extraction of alkaloids from T. iboga root bark was optimized and simplified to use only diluted vinegar and ammonia, and was successfully applied to related alkaloids from Voacanga africana bark also. The alkaloids were converted to their hydrochlorides and purified, and the minor alkaloids were recovered.
Asunto(s)
Alcaloides/química , Alcaloides/síntesis química , Ibogaína/análogos & derivados , Plantas Medicinales/química , Tabernaemontana/química , Alcaloides/economía , Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/química , Cromatografía en Capa Delgada , Ibogaína/síntesis química , Ibogaína/química , Alcaloides Indólicos/síntesis química , Alcaloides Indólicos/química , Estructura Molecular , Corteza de la Planta/química , Raíces de Plantas/química , Trastornos Relacionados con Sustancias/tratamiento farmacológicoRESUMEN
We have concluded initial preclinical studies with synthetic trioxanes numbered 3-9 and have compared them with artemisinin (numbered 1) using CD-1 mice infected with Plasmodium berghei. Based on their antimalarial effectiveness in mice, two of these synthetic trioxanes were selected for evaluation in Aotus monkeys infected with multidrug-resistant (MDR) P. falciparum. Trioxane numbered 8 (12 and 48 mg/kg), trioxane numbered 9 (12 and 48 mg/kg) and arteether (numbered 2, 48 mg/kg) were administered intramuscularly in three 12-hr doses to A. lemurinus lemurinus (Panamanian owl monkeys) infected with the Vietnam Smith/RE strain of P. falciparum and monitored for parasitemia. Trioxane numbered 8 at 12 mg/kg cleared parasitemia in two monkeys, but recrudescence occurred in one animal. Treatment of the recrudescent infection with 48 mg/kg was curative. Infections in two monkeys treated initially with 48 mg/kg were cured (six-month follow-up). Trioxane numbered 9 produced a similar outcome: 12 mg/kg suppressed parasitemia in two monkeys but was not curative; however, 48 mg/kg cured infections in all four monkeys treated. These preliminary observations show synthetic trioxanes numbered 8 and 9 to be as effective as arteether (numbered 2) against MDR in P. falciparum in the Aotus monkey.
Asunto(s)
Antimaláricos/uso terapéutico , Artemisininas , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Compuestos Heterocíclicos/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Malaria/tratamiento farmacológico , Plasmodium berghei , Animales , Antimaláricos/síntesis química , Aotus trivirgatus , Hidrocarburos Aromáticos con Puentes/síntesis química , Compuestos Heterocíclicos/síntesis química , Ratones , Estructura Molecular , Sesquiterpenos/uso terapéuticoRESUMEN
8,9-Dioxo-6-phenyl-1-aza-7-oxabicyclo[4.2.1]nonane (1) and 9,10-dioxo-7-phenyl-1-aza-8-oxabicyclo[5.2.1]decane (2), examples of anti-Bredt bicyclic 2,4-oxazolidinediones, were investigated as anticonvulsants in mice. Compound 2 was the more potent (anti-MES ED50 = 66 mg/kg), and its in vivo anti-MES effect was consistent with its in vitro potency of binding to the voltage-sensitive sodium channel (IC50 = 160 microM for the inhibition of binding of [3H]BTX-B), suggesting that 2 may be a new class I anticonvulsant. Several partial structures of 2, either monocyclic lactams or monocyclic 2,4-oxazolidinediones, were also evaluated in these assays, but no correlation was observed between sodium channel binding and anti-MES effects. A significant finding was that monocyclic 5-alkyl-5-phenyl-2,4-oxazolidinediones provided relatively potent, nontoxic, broad-spectrum anticonvulsants.
Asunto(s)
Anticonvulsivantes/síntesis química , Compuestos Bicíclicos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/síntesis química , Neuronas/metabolismo , Oxazoles/síntesis química , Canales de Sodio/metabolismo , Animales , Anticonvulsivantes/metabolismo , Anticonvulsivantes/farmacología , Sitios de Unión , Compuestos Bicíclicos con Puentes/metabolismo , Compuestos Bicíclicos con Puentes/farmacología , Corteza Cerebral/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Ratones , Oxazoles/metabolismo , Oxazoles/farmacología , Relación Estructura-Actividad , Sinaptosomas/efectos de los fármacosRESUMEN
The synthesis of two new series of 3,8-diazabicyclo [3.2.1] octane derivatives is described. The first series includes some 3-(or 8)-allyl and 3-(or 8)-(3,3-dimethylallyl) derivatives of 3,8-diazabicyclo [3.2.1] octane and 3,8-diazabicyclo [3.2.1] octane-2-one. The second series includes some esters and carbamates of 3-(3-hydroxy-3-methyl)butyl-3,8-diazabicyclo [3.2.1] octane. Two new 3,8-diazabicyclo [3.2.1] octane derivatives structurally related to propoxyphene are also described. Some pharmacological data of these compounds are reported.