N Cyclopropylmethyl

Naltrexone hydrochloride dihydrate (l-7V-cyclopropylmethyl-7,8-dihydro-14-hydroxy-morphinan-6-one hydrochloride) [16676-29-2] M 413.9, m 274-276°, [a] -173° (c 1, H2O), pKEst(i) 6 (N-cyclopropylmethyl), pKEst(i) (phenolic OH). This narcotic antagonist has been purified by recrystn from MeOH and dried air. The free base has m 168-170° after recrystn from Me2CO. [Cone et al. J Pharm Sci 64 618 7975 Gold et al. Med Res Rev 2 211 7952.]... 

Preparation of2-(N-Phthalimidoacetyl-N-Cyclopropylmethyl)-Amino-5-Chlorobemophenone To a solution of 36.0 g (0.126 mol) of 2-cyclopropylmethylamino-5-chlorobenzophenone in 500 ml of tetrahydrofuran is added 50.7 g (0.252 mol) of phthalimidoacetyl chloride. 

The resulting solution is refluxed for 16 to 24 hours, the solvent removed under vacuum, the residual oil crystallized from 200 ml of ethanol and recrystallized from 500 ml of 80% ethanol-20% tetrahydrofuran giving 44.7 g of 2-(N-phthalimidoacetyl-N-cyclopropylmethyl)-amino-5-chlorobenzophenone, MP 163 to 164°C (75% yield). 

To a solution of 39.5 g (0.0845 mol) of 2-(N-phthalimidoacetyl-N-cyclopropylmethyl)amino-5-chlorobenzophenone in a mixture of 423 ml of chloroform and 423 ml of ethanol Is added 9.52 g (0.1903 mol) of hydrazine hydrate and 9.52 ml of water. This solution is allowed to stand at room temperature. In 3 hours a precipitate begins to form in the solution. After standing 16 to 24 hours a voluminous pulpy white precipitate forms. The solvents are removed under vacuum while keeping the temperature under 40 0 and the residue is partitioned between dilute ammonia water and ether. 

N-cyclopropylmethyl 6,14-endo-ethano-7a-[(1S)-1 -hydroxy-1,2,2-trimethyIpropyl]-tetrohydronorthebaine (III)... 

N-(cyclopropylmethyl) a, a, a trlf luorO 2, dini tro-N-propyl p-toluidine... 

Homologation of the N-substituent beyond ethyl generally abolishes activity (22). N,N-dialkylation does not lead to active compounds, even with 3,4-meth-ylenedioxy substitution (197). It should be noted, however, that only a few N,N-dialkyl compounds have been clinically evaluated. N-alkylation also decreases in vitro serotonin receptor affinity (80). Certain N-propyl, N-cyclopropylmethyl, and N-allyl derivatives show weak antagonism against mescaline-induced disruption of swimming behavior in mice (50). 

The most important and dramatic change results when the N-methyl group of morphine is replaced by an N-alkene or N-cyclopropylmethyl group. The resulting compounds show antagonist properties. 

The pharmacological effects of iV-allyl- and N-cyclopropylmethyl-6/3-azidodeoxydihydronormorphine have been compared with those of naloxone... 

Chemical Name Af-(cyclopropylmethyl)-2,6-dinitro-lV-propyl-4-trifluoromethylaniline N-(cyclopropylmethyl)-2,6-dinitro-Af-propyl-4-(trifluoromethyl) benzenamine... 

S-CHR — Li/Keton] Thiobutansaure 3,3-Dimethyl-2-oxo- -tert.-butylamid E5, 1241 (Keton/SOCl2 Amin) Thiocarbamidsaure N-Cyclopropylmethyl-N-propyl- -S-ethylester E4, 296 (Cl - ... 

C14H16 1,3-dimethyl-6-ethyl naphthalene 39622-45-2 585.41 52.148 2 27480 C14H18N604 adenosine-6 -(N-cyclopropylmethyl)carboxamide 58048-25-2 366.75 31.244 1,2... 

Keating and Skell" and later Laurent and Thomalla" have found that a similar mixture of products was obtained in the anodic oxidation of either cyclobutanecarboxylic acid, allylacetic or cyclopropaneacetic acid. They accounted for these results by a rapid equilibria among the carbocations initially formed. A similar observation is that in the anodic oxidation of the corresponding iodo reactants in acetonitrile N-(cyclopropylmethyl)acetamide was found in each product mixture". It is noteworthy that the same identity in products also holds for the chemical reactions of solvolysis and... 

Schmidhammer H, Burkard WP, Eggstein-Aeppli L, Smith CFC (1989) Synthesis and biological evaluation of 14-alkoxymorphinans. 2. (-)-N-(cyclopropylmethyl)-4, 14-dimethoxy-morphinan-6-one, a selective p opioid receptor antagonist. J Med Chem 32 418—421... 

Jiang Q, Sebastian A, ArcherS, Bidlack JM (1994) 5P-Methyl-14P-(p-nitrocinnamoylamino)-7,8-dihydromorphinone and its corresponding N-cyclopropylmethyl analogue, N-cyclopro-pylmethylnor-5 P-methyl-14P-(p-nitrocinnamoylamino)-7,8-dihydromorphinone mu selective irreversible opioid antagonists. J Pharmacol Exp Ther 268 1107-1113... 

Jiang Q, Seyedmozaffari A, Archer S, Bidlack JM (1993) Pharmacological study of 14-beta-(thioglycolamido)-7,8-dihydro-n-cyclopropylmethyl-normorphinone (N-CPM-TAMO). J Pharmacol Exp Ther 264 1021-1027... 

Gates and Klein-3 have prepared some metamorphinan derivatives (III) where the ethanimine bridge terminates at C h rather than C] 3. The N-methyl derivative was tested as an analgesic and the N-cyclopropylmethyl compound as an analgesic... 

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