Dibenzo[a,d]cycloheptene and related compounds. II. The synthesis of some 11-substituted dibenzo[b,e]azepin-6-one, 5-substituted dibenzo[a,d]cycloheptene, and 12-substituted dibenzo[a,d]cyclooctene derivatives

Ackermann, Kathrin; Chapuis, Jacques; Horning, D. E.; Lacasse, G.; Muchowski, Joseph M.

doi:10.1139/v69-717

Cited by 20 publications

(7 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It would also be of interest to determine if the thioxanthene compounds 6 (inactive at 10 mg/kg) had analgesic activity at the dose levels at which compounds 3 and 5 were reported to be active (10-40 mg/kg). cyclooctene (8, n = 3) were prepared according to a published procedure (1).…”

Section: Methodsmentioning

confidence: 99%

Dibenzo[a,d]cycloheptene and Related Compounds. III. The Synthesis of Some Analogues of Methadone Containing the Dihydrodibenzo[a,d]cycloheptene and the Tetrahydrodibenzo[a,d]cyclooctene Ring Systems

Horning¹,

Muchowski²

1971

Can. J. Chem.

Self Cite

View full text Add to dashboard Cite

The synthesis and spectral properties of some two-and three-carbon ortho-bridged analogues of the analgesic methadone are described. These compounds were devoid of analgesic activity.Canadian Journal of Chemistry, 49, 485 (1971) Methadone (1, R = CH,), a clinically useful narcotic analgesic (2), was first prepared by Bockmuhl and Ehrhart (3) manner described in Scheme 1.'TO whom enquiries ~0tIcerning this paper should be ~h , alkylation of the cyanides 8 with 3-bromoaddressed.3Compound 2 was said (7) to be "quite toxic" and did 2-(tetrah~dro~~ran-2-~lox~)-~ro~ene (THP = not exhibit "promising analgesic activity", 3 had 1/20 of tetrahydropyran-2-yl), generated in situ (13), folthe activity of morphine (1125 methadone) in mice on lowed by acidic hydrolysis of the intermediate subcutaneous administration (8), 4 (R = R ' = CH3) was described (9) as showing "slight analgesia at 0.5-5 en01 ethers, produced the keto nitriles 9, which in mg/kg", 5 was reported (1 1) to possess "1/5 of the anal-turn were converted to the methadone-type nigesic activity of morphine (116 methadone) when used on experimental and 6 (X=H, C1) was not active triles 12 by a Leuckart reaction4 with dimethyl-(12) in mice or rats at 10 mg/kg (subcutaneous).formamide and formic acid. The transformation Can. J. Chem. Downloaded from www.nrcresearchpress.com by 18.236.120.13 on 05/11/18For personal use only.

show abstract

Section: Methodsmentioning

confidence: 99%

Dibenzo[a,d]cycloheptene and Related Compounds. III. The Synthesis of Some Analogues of Methadone Containing the Dihydrodibenzo[a,d]cycloheptene and the Tetrahydrodibenzo[a,d]cyclooctene Ring Systems

Horning¹,

Muchowski²

1971

Can. J. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…This was prevented by buffering the oxidation reaction with sodium acetate, thus providing aldehyde 24 in a 95% yield after chromatographic purification. Condensation of aldehyde 24 with trimethylsilyl cyanide in the presence of a catalytic amount of zinc iodide followed by borane reduction of the intermediate a-(silyloxy)nitrile gave 2-amino-l-(2-((2,3-dimethoxyphenyl)methyl)phenyl)ethanol, 25, in an overall 91% yield from the aldehyde. This finally provided the precursor for the key dihydroanthracene intermediate 19.…”

Section: Chemistrymentioning

confidence: 99%

“…mp 134-135 °C; NMR (CDClg) 8.01 (1H, d, J = 7.7 Hz, ArH), 7.40 (1H, dd, J = 7.5 and 7.6 Hz, ArH), 7.27 (1H, dd, J = 7.5 and 7.8 Hz, ArH), 7.14 (1H, d, J = 7.8 Hz, ArH), 6.94 (1H, dd, J = 7.7 and 8.2 Hz, ArH), 6.79 (1H, d, J = 8.2 Hz, ArH), 6.60 (1H, d,J = 7.7 Hz, ArH), 4.43 (2H, s, CH2), 3.84 (3H, s, OCH3), 3.64 (3H, s, OCH3); CIMS m/z (relative intensity) 273 (MH+, 7), 272 (25), 255 (100); EIMS m/z (relative intensity) 272 (M+, 100), 255 (36), 239 (78). Anal.…”

Section: -((Jv-(/s^s-dimethoxyethylmentioning

confidence: 99%

Synthesis and Evaluation of 6,7-Dihydroxy-2,3,4,8,9,13b-hexahydro-1H-benzo[6,7]cyclohepta[1,2,3-ef][3]benzazepine, 6,7-Dihydroxy-1,2,3,4,8,12b-hexahydroanthr[10,4a,4-cd]azepine, and 10-(Aminomethyl)-9,10-dihydro-1,2-dihydroxyanthracene as Conformationally Restricted Analogs of .beta.-Phenyldopamine

et al. 1995

View full text Add to dashboard Cite

The present study was designed to define the geometry of the hydrophobic accessory region for binding of dopamine D1 receptor ligands and to assess the relative importance of ethylamine side chain conformation for receptor affinity. Three compounds, 6,7-dihydroxy-2,3,4,8,9,13b-hexahydro-1H-benzo[6,7]cyclohepta[1,2, 3-ef][3]benzazepine, 4, 6,7-dihydroxy-1,2,3,4,8,12b-hexahydroanthr[10,4a,4-cd]aze pin e, 5, and 10-(aminomethyl)-9,10-dihydro-1,2-dihydroxyanthracene, 6, were synthesized as conformationally restricted analogs of beta-phenyldopamine. Molecular modeling studies were performed to compare these three compounds with the high-affinity D1 agonists dihydrexidine (DHX), 2, and SKF 38393, 3. The beta-phenyl moieties in the target compounds are constrained by means of either an ethyl (4) or methylene (5 and 6) bridge. The compounds adopt minimum-energy conformations in which the beta-phenyl group is approximately -22 degrees (4), -12 degrees (5), and -30 degrees (6) from coplanarity with the catechol ring. These compounds also embody either a freely rotating (6) or a rigidified gauche (4 and 5) rotameric conformation of the dopamine ethylamine side chain, the latter nearly perfectly superimposible on the benzazepine portion of SKF 38393. Radioligand competition experiments showed that compounds 4, 5, and 6 have only micromolar affinity for both the D1 and D2 dopamine receptor subtypes. The low affinity of 4-6, relative to 2 and 3, may be due to improper orientation of the beta-phenyl moiety and provides important information about the three-dimensional orientation of the hydrophobic accessory binding domain of the dopamine D1 receptor. In addition, the negligible affinity of 6, as compared to 2 and 3, indicates that the rotameric positioning of the ethylamine side chain may not be a primary determinant of receptor affinity.

show abstract

“…' (26). Following a modified method [26], NaH (80% in mineral oil; 2.3 g, 80 mmol) was washed twice with pentane, and then dry DMSO (125 ml) and 25 (1 1.8 g, 78.6 mmol) were added at r.t. After 10 rnin at r.t., trimethylsulfonium iodide (16.3 g, 80 mmol) was added in two portions, and the mixture was stirred at r.t. for 24 h. The soln. was poured into a large excess of ice/water, and the unstable epoxide was isolated by extraction with Et,O.…”

Section: Experimental Partmentioning

confidence: 99%

New Irone‐Related Constituents from the essential oil of Iris germanica L.

Maurer

Hauser

Froidevaux

1989

Helvetica Chimica Acta

View full text Add to dashboard Cite

Structure Elucidations and PartialSyntheses. -The structures of the new constituents 1-20 were established by 360-MHz 'H-NMR spectroscopy (making extensive use of selective decoupling techniques) in combination with IR and MS. For the compounds 1,6,7,9,10, and 11, the spectral data were in agreement with published ones, and for 2-4, 8, and 12-18, the structures derived from the spectra were confirmed by partial synthesis. The structures of the remaining constituents 5, 19, and 20 follow unambiguously from their spectral data.Optical rotations could be measured for cis-a-irone, cis-y-irone, 6, 16, and 17. These compounds all belong to the same enantiomeric series (2S)3), as shown by chemical correlation with optically active cis-a-irone and cis-y-irone of known [4] absolute configuration. We therefore assume the newly identified compounds to possess the chiralities shown in Fig. 24). ,The numbering of the irones follows the IUPAC rules for the nomenclature of carotenoids. 4,trans-a-Dihydroirone (10) is assumed to possess (2R) chirality based on Rautenstrauch's work [4].

show abstract

Dibenzo[a,d]cycloheptene and related compounds. II. The synthesis of some 11-substituted dibenzo[b,e]azepin-6-one, 5-substituted dibenzo[a,d]cycloheptene, and 12-substituted dibenzo[a,d]cyclooctene derivatives

Cited by 20 publications

References 6 publications

Dibenzo[a,d]cycloheptene and Related Compounds. III. The Synthesis of Some Analogues of Methadone Containing the Dihydrodibenzo[a,d]cycloheptene and the Tetrahydrodibenzo[a,d]cyclooctene Ring Systems

Dibenzo[a,d]cycloheptene and Related Compounds. III. The Synthesis of Some Analogues of Methadone Containing the Dihydrodibenzo[a,d]cycloheptene and the Tetrahydrodibenzo[a,d]cyclooctene Ring Systems

Synthesis and Evaluation of 6,7-Dihydroxy-2,3,4,8,9,13b-hexahydro-1H-benzo[6,7]cyclohepta[1,2,3-ef][3]benzazepine, 6,7-Dihydroxy-1,2,3,4,8,12b-hexahydroanthr[10,4a,4-cd]azepine, and 10-(Aminomethyl)-9,10-dihydro-1,2-dihydroxyanthracene as Conformationally Restricted Analogs of .beta.-Phenyldopamine

New Irone‐Related Constituents from the essential oil of Iris germanica L.

Contact Info

Product

Resources

About