Derivate des 2-Amino-1,2,3,4-tetrahydro-naphthalins, 5. Mitt. Synthese des trans-2-Amino-3,5,8-trihydroxy-1,2,3,4-tetrahydronaphthalins und seiner N-substituierten Derivate

Derivatives of 2-Amino-1,2,3,4-tetrahydronaphthalene, V: Syntheses of trans-2-Amino-3,5,8-trihydroxy-1,2,3,4-tetrahydronaphthalene and N-Substituted Derivatives. The trans-aminoalcohol 14 was synthesized by ammonolysis of 5,8-dimethoxy-2,3-epoxytetraline (I) . The hydrochloride of 14 was further demethylated and trans-2-amino-3,5,8-trihydroxy-tetraline hydrobromide (14a ) was obtained. Similarly the hydrobromides of the 3,5,8-trihydroxy-analogues 1a–13a were obtained from the N-substituted trans-2-amino-3-hydroxy-5,8-dimethoxytetraline hydrochlorides 1–13 .     

Derivate des 2-Amino-1,2,3,4-tetrahydronaphthalins, 6. Mitt. IR-Spektroskopische Konformationsermittlung einiger 2-Amino-3-hydroxy-5,8-dimethoxy-1,2,3,4-tetrahydronaphthaline

Derivatives of 2-Amino-1,2,3,4-tetrahydronaphthalene, VI: IR-Spectroscopic Determination of the Conformational Equilibrium of Some 2-Amino-3-hydroxy-1,2,3,4-tetrahydronaphthalenes. The conformational characteristics of cis- and trans-2-amino-3-hydroxy-5,8-dimethoxytetralins and some N-substituted derivatives were investigated by analysing their IR spectra. A high degree of hydrogen bonding for the trans compounds and a preferred diequatorial conformation were established. The spectra of the cis isomers show the presence of a larger population of the rotamer with axial OH group. The scheme for the synthesis of cis-AT is presented.     

Derivate des 2-Amino-1,2,3,4-tetrahydronaphthalins,III. Synthese einiger N'-substituierter N-(trans-3-Hydroxy-1,2,3,4-tetrahydro-2-naphthyl)-piperazine

Derivatives of 2-Amino-1,2,3,4-tetrahydronaphthalene, III: Synthesis of Some N'-Substituted N-(trans-3-Hydroxy-1,2,3,4-tetrahydro-2-naphthyl)piperazines The synthesis of the N'-substituted N-(trans-3-hydroxy-1,2,3,4-tetrahydro-2-naphthyl)piperazines 2 – 5 and of trans-2-morpholino-3-hydroxy-1,2,3,4-tetrahydronaphthalene ( 6 ), starting from 2,3-epoxytetralins 1 , is reported. The new Mannich bases 3 show hypotensive and antiarrhythmic activities.     

Derivatives of 2-Amino-1,2,3,4-Tetrahydronaphthalene,VIII.1) Isomerization of trans-2-Acetamido-3-hydroxy-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene and Hydrolysis of 5,8-Dimethoxy-2-methyl-3a,4,9,9a-tetrahydronaphth[2,3-d]oxazoline Hydrochloride

The isomerization of trans-2-acetamido-3-hydroxy-5,8-dimethoxytetraline (1) under the action of hydrogen chloride was investigated. Hydrolysis of 5,8-dimethoxy-2-methyl-3a,4,9,9a-tetrahydronaphth[2,3-d]oxazoline hydrochloride (2) leads to cis-2-amino-3-hydroxy-5,8-dimethoxytetraline (3) .     

Derivate des 2-Amino-1,2,3,4-tetrahydronaphthalins, 7. Mitt. Aroylester des cis- und trans-2-Dimethylamino-3-hydroxy-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalins

Derivatives of 2-Amino-1,2,3,4-tetrahydronaphthalene, VII: Aroyl Esters of cis- and trans-2-Dimethylamino-3-hydroxy-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalenes By acylation of cis- and trans-2-dimethylamino-3-hydroxy-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene (2) with the chlorides of some aromatic acids, the aroyl esters 1 were obtained. The new compounds show spasmolytic and local anesthetic activities.     

N-Arylacyl- und N-Arylalkyl-Derivate von 2-Amino-1-butanol mit zwei Chiralitätszentren

N-Arylacyl and N-Arylalkyl Derivatives of 2-Amino-1-butanol with Two Chiral Centers Syntheses of all optical isomers of 2-(N-(2-phenylbutyryl)amino]-1-butanols 1a–d and 2-[N-methyl-N-(2-phenylbutyryl)amino]-1-butanols 2a–d are reported. Reduction of the amides leads to the amines 3a–d and 4a– d . Each of these compounds has two chiral centers, for which the absolute configurations are established.     

Verbindungen mit potentiell positiv inotroper Wirkung, 1. Mitt. N-Substituierte 3-Amino-2-cyclopentenone aus partiell hydrierten 2-Phenanthrylaminen

Compounds with Potentially Positive Inotropic Activity, I: N-Substituted 3-Amino-2-cyclopentenones from Partially Hydrogenated 2-Phenanthrylamines The synthesis of partially hydrogenated 2-phenanthrylamines and their reactions with 1,3-cyclopentanedione to N-substituted 3-amino-2-cyclopentenones is described.     

Thiocyanatocarbonsäurehydrazide und ihre Isomerisierungsprodukte, 1. Mitt.: Synthesen von Derivaten des 3-Amino-2-thiohydantoins

Thiocyanatocarboxylic Hydrazides and Their Isomerization Products, I: Syntheses of 3-Amino-2-thiohydantoin Derivatives The reaction of α-chlorocarboxylic N²,N²-dialkyl-, alkyl-aryl- or diaryl hydrazides 1 with potassium thiocyanate in acetonitrile proceeds via thiocyanates and isothiocyanates 2 and 3 , respectively, to yield the 3-amino-2-thiohydantoins 5 . Methylation of these products leads to derivatives of the 1 -amino-2-methylthioimidazolinone 4 .     

Nitroketenaminale, 5. Mitt.: Synthese von N2-substituierten 2-Amino-3-nitropyridinen als Vorstufen von Pyrido[2,3-b]pyrazinen (3-Desazapteridinen)

Nitroketeneaminals, V¹) Synthesis of N²-Substituted 2-Amino-3-nitropyridines as Educts for Pyrido[2,3-b]pyrazines (3-Deazapteridines) ^N2-Substituted 2-amino-3-nitropyridines are obtained from the nitroketeneaminals 3 and the 1,3-biselectrophiles 1 and 2 . Oxidation and catalytic hydrogenation of 13 yields the 1,2,3,4-tetrahydropyrido[2,3-b]pyrazine 17 .     

Synthesis of Potentially Antineoplastic Derivatives of N-[N-(2-Chloroethyl)-N-nitrosocarbamoyl]amino Acids

The synthesis of N-[N-(2-chloroethyl)-N-nitrosocarbamoyl]amino acids and their anilides, congeners of N-(2-chloroethyl)-N-nitrosoureas, as potential antineoplastic substances is reported. N-[N-(2-chloroethyl)-N-nitrosocarbamoyl]amino acids are prepared by reaction of amino acids with N-(2-chloroethyl)-N-nitrosocarbamoyl azide. Corresponding anilides and toluidides are obtained by condensation of the primary reaction products with aniline and toluidine using dicyclohexylcarbodiimide (DCC).     

Disposition of a New Alkylating Agent [14C]Mitoclomine (N,N-Bis(2′-Chloroethyl)4-Amino-2-Methyl-1-Methoxy-naphthalene)

1. The absorption, distribution and elimination of a new alkylating agent, N,N-bis(2′-chloroethyl)4-amino-2-methyl-1-methoxynaphthalene (mito-clomine), labelled with ¹⁴C either in the dichloroethyl group or in the methoxy group, have been studied in mice and rats.

2. Expired ¹⁴CO₂ of rats given [chloroethyl-¹⁴C]- or [methoxy-¹⁴C]mitoclomine amounted to 1·0 and 35% dose respectively, indicating that O-dealkylation occurs.

3. The part of the molecule carrying the cytotoxic group displayed a high affinity for lymphoid organs (thymus, spleen). This could explain some biological properties of this drug, especially the selective effects of mitoclomine on circulating lymphocytes.     

2-Amino-2′-[18F]fluorobenzhydrols,intermediates for the synthesis of [2′-18F]-1,4-benzodiazepine-2-ones

A method for synthesizing ¹⁸F-labelled 2-amino-2′-fluorobenzhydrols under nocarrier-added conditions for use as radiolabelled intermediates in the synthesis of[2′-¹⁸F]-1,4-benzodiazepine-2-ones is presented. Anilinodichloroborane reagents were formed by the reaction of boron trichloride with 4-chloro-N-methylaniline, 6a , 4-nitro-N-methylaniline, 6b , 4-nitro-N-ethylaniline, 6c , and 4-chloro-N-(2,2,2-trifluoroethyl)aniline, 6d . 2-[¹⁸F]Fluorobenzaldehyde, 5 , synthesized in 55–70% yields by the nucleophilic aromatic substitution of 2-nitrobenzaldehyde with the Kryptofix/K⁺ complex of [¹⁸F]F⁻, was subsequently reacted with the anilinodichloroborane coupling reagents with aromatic substitution occurring ortho to the amino group. The resulting 2-amino-2′-[¹⁸F]fluorobenzhydrols, 7a - 7d , were produced in conversions of 60–95% with reaction time ⩽ 10 min at room temperature or 60°C, depending on the aniline used. The total synthesis time, including evaporation of the target water, was 60–65 min. The total radiochemical conversions were of the order of 50–65% for 7a - 7c and 35–45% for 7d , decay-corrected and based on [¹⁸F]F⁻.     

Synthesis and Antitumor Activity of Novel Dibutyltin Carboxylates of Aminoglucosyl Derivatives

In this study, di‐n‐butyltin(IV) oxide was reacted with the amino glucose analog, cis‐4‐[N‐(1′,3′,4′,6′‐tetra‐O‐benzoyl‐2‐deoxy‐glucopyranosyl)imido]‐4‐oxo‐2‐butenoic acid ( 1a ) and o‐[N‐(1′,3′,4′,6′‐tetra‐O‐benzoyl‐2‐deoxy‐glucopyranosyl) carbamoyl] benzoic acid ( 2a ) to give the complexes bis‐{cis‐4‐[N‐(1′,3′,4′,6′‐tetra‐O‐benzoyl‐2‐deoxy‐glucopyranosyl)imido‐4‐oxo‐2‐butenoic acid]‐di‐n‐butyltin} carboxylate ( 1 ) and bis‐{o‐[N‐(1′,3′,4′,6′‐tetra‐O‐benzoyl‐2‐deoxy‐glucopyranosyl) carbamoyl‐benzoic acid]‐di‐n‐butyltin}carboxylate ( 2 ). These two compounds were then characterized by IR, NMR and MS. In vitro tests showed that both compounds have high cytotoxicity in four tumor cell lines (P388, HL‐60, A549 and BEL‐7402). Clonogenic assays demonstrated that both compounds 1 and 2 have hematopoietic cell toxicity at 10^?6 m .     

Synthesen von 13C- und 14C-markiertem trans-2-Amino-2-methyl-N-(4-nitroxycyclohexyl)-propionsäureamid (BM 12.1179)

Syntheses of ¹³C- and ¹⁴C-labelled trans-2-Amino-2-methyl-N-(4-nitroxycyclohexyl)-propionamide (BM 12.1179) The ¹³C- and ¹⁴C-labelled derivatives of the vasodilating nitric acid ester trans-2-amino-2-methyl-N-(4-nitroxycyclohexyl)-propionamide (BM 12.1179) ( 1 ) have been synthesized starting from the sterically hindered α-amino-isobutyric acid ( 2 ) via the oxazolone (synthesis of ¹³C-BM 12.1179) and the acid chloride (synthesis of ¹⁴C-BM 12.1179). Various amine-protecting groups and methods for activating the carboxy-function are compared.     

Derivatives of 2-amino-1,2,3,4-tetrahydronaphthalene, IX: Structure-activity relationships of cis- and trans-2-amino-5,8-dimethoxytetralin-3-ols and some analogues

The structure-activity relationships of cis- and trans-2-amino-5,8-dimethoxytetralin-3-ols and some of their analogues are discussed. A correlation was established between the stereochemical characteristics of the compounds and their pharmacological effects.     

Cer(IV)oxidationen von β-Aminoketonen, 8. Mitt.: Synthese von im Piperidinteil verschieden substituierten 1,2,3,4-Tetrahydroisochinolinen

Cerium(IV) Oxidations of β-Aminoketones, VIII¹⁾: Synthesis of 1,2,3,4-Tetrahydroisoquinolines with Differently Substituted Piperidine Parts 1- and 3-Alkyl- and/or aryl substituted tetrahydroisoquinolines are obtained by oxidative cyclisation of N-benzyl-β-aminoketones with cerium(IV) sulphate. In nearly all cases formation of mixtures of diastereomeres is observed. If the ketone function is replaced with COOR-, CN-, CHO and NO₂-groups no cyclisation occurs under standard reaction conditions. The products of hydrolysis, N-benzyl-N-methylaminopropionic acid, and of oxidation in benzylic position, benzaldehyde and benzoic acid, are mainly formed during the reaction. The oxidation of the N-benzylaminopropionaldehydacetal 1k yields the isoquinolinedione 4k .     

Cer(IV)-Oxidationen von β-Aminoketonen. 3. Mitt.: Ein Syntheseweg zu 4-spirosubstituierten 1,2,3,4-Tetrahydroisochinolinen

Cerium(IV) Oxidations of β-Aminoketones. Part III: A Pathway to 4-Spiro-Substituted 1,2,3,4-Tetrahydroisoquinolines Substituted 2′-methyl-2′,3′-dihydro-1′H-spiro[cycloalkan-1,4′-isoquinolin]-2-ones and -[chroman-3,4′-isoquinolin]-4-ones are synthesized by cerium(IV) oxidation of (N-benzyl-N-methylamino)methylcycloalkan-1-ones or corresponding substituted chromanones.     

Cer(IV)sulfat-Oxidationen: Intramolekulare Cyclisierung von N-Benzyl-β-aminoketonen zu 4-Benzoyl-1,2,3,4-tetrahydroisochinolinen

Oxidations with Cerium(IV) Sulfate: Intramolecular Cyclization of N-Benzyl-β-aminoketones Yielding 4-Benzoyl-1,2,3,4-tetrahydroisoquinolines Preparation and regiospecific cerium(IV) sulfate oxidation of the substituted N-benzyl-β-aminoketones 3 are described. 4-Benzoyl-1,2,3,4-tetrahydroisoquinolines 4 so obtained are reduced by sodium borohydride.     

Amino Acid Derivatives,Part 4: Synthesis and Anti‐HIV Activity of New Naphthalene Derivatives

A new series of 2‐(naphthalen‐2‐yloxy)‐N‐[(aryl‐5‐thioxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐3‐yl)methyl] acetamides 5a–f was synthesized from naphthalene‐derived glycine derivative 2 via the hydrazinoacetamide analogs 4a–f . Alternatively, treatment of 4a with H₂SO₄ afforded 2‐(naphthalen‐2‐yloxy)‐N‐((5‐(phenylamino)‐1,3,4‐thiadiazol‐2‐yl)methyl) acetamide 6a . Alkylation or sulphonylation of 5a afforded the S‐alkylated derivatives 7 and 8 , respectively. Interestingly, treatment of 3 with methoxide ion gave the triazine derivative 9 . The synthesized compounds have been screened for their inhibitory activity against HIV‐1 and HIV‐2 in MT‐4 cells. However, 7 was found to be the potent inhibitor in vitro for the replication of HIV‐1 (EC₅₀ = 0.20 μg/mL), suggesting a new lead in the development of an antiviral agent.     

Synthesis and Anticonvulsant Activity of N‐(2‐Hydroxy‐ethyl)amide Derivatives

A series novel of N‐(2‐hydroxyethyl)amide derivatives was synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test (Tox). The maximal electroshock test showed that N‐(2‐hydroxyethyl)decanamide 1g , N‐(2‐hydroxyethyl)palmitamide 1l , and N‐(2‐hydroxyeth‐yl)stearamide 1n were found to show a better anticonvulsant activity and also had lower toxicity than the marked anti‐epileptic drug valproate. In the anti‐MES potency test, these compounds exhibited median effective doses (ED₅₀) of 22.0, 23.3, 20.5 mg/kg, respectively, and median toxicity doses (TD₅₀) of 599.8, >1000, >1000 mg/kg, respectively, resulting in a protective index (PI) of 27.5, >42.9, >48.8, respectively. This is a much better protective index than that of the marked anti‐epileptic drug valproate (PI = 1.6). To further investigate the effects of the anticonvulsant activity in several different models, compounds 1g , 1l , and 1n were tested having evoked convulsions with chemical substances, including pentylenetetrazloe, isoniazide, 3‐mercaptopropionic acid, bicuculline, thiosemicarbazide, and strychnine.