Trans-2- cyclopropylamine

The 2-phenylcyclobutylamines Structures 14 and 15 have also been prepared (161). In contrast to the cyclopropylamine, however, 15 showed no clinical activity following oral administration of a dose up to 25 mg of the racemic hydrochloride (199). The trimethoxy congener 14 has not been tested. The appropriately ring-substituted tran.s-2-phenylcyclopentyl or cyclohexylamines have not been reported. Based on the apparent lack of activity for 15, as well as the lack of activity for alpha-ethyl phenethylamine derivatives, however, these might be predicted to be inactive. 

Jacob, J. N., and Nichols, D. E. (1982) Isomeric cyclopropyl ring-methylated homologues of trans-2-(2,5-dimethoxy-4-methylphenyl)cyclopropylamine, an hallucinogen analogue. J. Med. Chem., 25 526-530. 

Die BECKMANN-Umlagerung des Cyclopropylmethylketoxims wurde zu einer brauchbaren Darstellungsmethode des Cyclopropylamins aus-gebaut (175). Trans-1.2.3-Cyclopropantricarbonsaureathylester liefert beim CuRTius-Abbau 1.2.3-Cyclopropantriamin (97). 

Condensation of m-fluorobenzaldehyde with malonic acid leads to the trans cinnamic acid 96 acylation of the acid chloride with cyclopropylamine leads to amide 97 (cinflumide), a muscle relaxant [24]. 

With the recognition in the late 1960s that there are two forms of MAO (Section 1.1.1), potential therapeutic implications related to isozyme selectivity needed to be considered in MAO inhibitor development. (The early literature also reveals some lack of distinction between copper-containing and flavin-containing MAOs.) An important case in point involves the clinical side effects associated with the cheese effect (Section 1.2.1) that made clear that there would be important clinical advantages to having available isozyme-selective inhibitors [115]. Follow-up studies with the well-known cyclopropylamine inhibitor trans-2-phenylcyclopropylamine (8a) demonstrated that this clinically useful compound is an irreversible inhibitor of MAO, but that it had no selectivity toward either MAO A or B [116]. 

On the other hand, a recent crystallographic study revealed that the trans-2-phenylcyclopropylamine (8a) forms a cyclopropyl ring-opened adduct with MAO B at the flavin C(4a), and no evidence was obtained for inhibitor binding at Cys-365 [70,127]. From this observation, Edmondson and coworkers suggested [70] that the inhibition mechanism might be accommodated by a mechanism similar to that proposed by Sayre et al. for the quinone-mediated oxidative cleavage of cyclopropylamines [128]. 

We have examined the above-described series of trans- and c/s-2-fluoro-2-phenylcyclopropylamine analogues (60a-d, 61a-d) as inhibitors of recombinant human liver MAO A and B [134]. The presence of fluorine attached to a cyclopropane ring, especially for frans-isomer 8a, was found to result in an increase in inhibitory activity toward both MAO A and B (Table 4). In addition, p-substitution of electron-withdrawing groups, such as Cl and F, in the aromatic ring of the frans-isomers (60b-d) increased the inhibition of both enzymes. On the other hand, the introduction of fluorine at 2-position of c/s-isomer 8b resulted in loss of inhibitory activity for both MAO A and B, and no further p-aromatic substitution for c/s-isomer greatly affected on the inhibitory activity with either enzymes. In addition, both MAO A and B were selectively inhibited by the (1S,2S)-enantiomer of 60a, while no inhibition was observed with the (1f ,2f )-enantiomer [134]. As already described in the former section, several questions on the mechanistic pathway for MAO inhibition by cyclopropylamines still remain. However,... 

And, as a final note, be careful. The code TMT has two meanings. In the phenethylamine area it identifies the mescaline analog, 3,4,5-trimethoxytranylcypromine (or trans-2-(3,4,5-trimethoxyphenyl)cyclopropylamine). This is entry 56, page 607 of PIHKAL, and check there for further detail. Here, entries of multiply methylated tryptamines (with the one exception of DMT) will be preceded with the specific locations of the methyl groups. Those prefixes such as numbers of Greek letters. 

A solution of 1.5 g trans-2-(2,5-dimethoxy-4-mcthylphenyl)carbo-benzoxyamidocyclopropane in 120 mL MeOH containing 200 mg 10% Pd/C was shaken under hydrogen gas at 35 psig for 45 min. The solution was filtered through celite, and a sufficient amount of a solution of 5% HC1 in EtOH was added to the filtrate to make it acidic. Removal of all volatiles under vacuum gave a solid residue that was recrystallized from an EtOH/ether mixture to give 0.98 g of trans-2-(2,5-dimethoxy-4-methylphenyl)cyclopropylamine hydrochloride (DMCPA) as white crystals with a mp of 210-211 °C. 

Some of the major drugs in the category of MAOs include phenelzine, 50, moclobemide, 51, toloxatone, 52, and others. Tranylcypromine (trans-phenyl-cyclopropylamine), 53, was one of the first MAO inactivators approved for clinical use [6]. 

C9H10O4 2-hydroxyethyl 2-hydroxybenzoate 87-28-5 477.23 41.700 2 16903 C9H11N trans-2-phenyl cyclopropylamine 3721-28-6 499.21 43.808 2... 

For some years the mitochondrial flavoenzyme monoamine oxidase (MAO) was the target of selective inhibition in the development of tranquillizing drugs " One potent inhibitory class was that of cyclopropylamines of which tranylcypramine (164) (trans-2-phenylcyclopropylamine) was a successful, albeit clinically dangerous and eventually unusable agent °. Tranylcypramine (164) and analogous cyclopropylamines turn out to... 

More detailed isotopic labeling studies have also been performed. Hydroxycyclopropanation of trans-f.3-deutero-styrene 273 under Kulinkovich conditions furnishes m-2-phcny 1-1 -cyclopropanol, 274, indicating retention of configuration at the carbon bound to titanium and is consistent with frontside attack of the Ti-C bond on a titanium-bound carbonyl.220 For the related de Meijere cyclopropylamine synthesis, the opposite outcome has been observed where a 3 1 mixture of A, Wdimethyl-W(/ra t-3-deutero-/ra j-2-phenylcyclopropyl)amine 278 and -dim ethyl-. V-((7.i-dcutcro-t7r-2-phony Icyclopropy I )amine 277 is produced. These products require inversion of configuration at the carbon bound to titanium and are consistent with a W-shaped transition structure for ring closure (Scheme 46). 

Dimethyl(succinimido)sulfonium fluorosulfate 2, easily prepared from /V-chlorosuccinimide (1), dimethyl sulfide, and methyl fluorosulfate, reacted with 1-dialkylaminocycloalkenes 3 to give fair yields of (2-dialkylaminocycloalk-l-enyl)dimethylsulfonium fluorosulfates 4 or their thermally rearranged allylic isomers 5.22 23 At elevated temperatures 4 or 5, respectively, reacted with nucleophiles Nu to give c -bicyclo[n.l.O]alkanes 8 or 9 via (Z,Z)-2-aminoallyl cation 6 or trans-bicyclo[n.l. 0]alkanes 12 via ( , Z)-2-aminoallyl cation 10, in fair to excellent yield.23 " 42 Normally, ra-annulated cyclopropylamines 8, resulting from kinetically preferred attack of... 

A great deal of attention has been focused on the interaction of monoamine oxidase with cyclopropylamine analogs, primarily through the efforts of Silver-man and co-workers, which has provided much of the basis for the proposed radical mechanism for the enzyme. The clinically utilized antidepressant trans-... 

It is known that the structure of the amines is the major factor determining the configuration of the products in aqueous deaminations. Kirmse s work included the following amines exo-norbornyl-2-amine (7.48), trans-4-(rerr-butyl)cyclohexyl-amine (7.49), (+)-(5)-l-methylpropylamine (7.50), (2i ,35)-l,2-dimethylbutylamine (7.51), cyclopropylamine (7.52) and its 2,2,3-trideuterated derivative (7.53), 4,4-dimethyladamantyl-2-amine (7.54) and its G 2r/-isomer. ... 

Asymmetric induction within 1,2-diphenylcyclopropane on photolysis in P-cyclodextrin has been studied.Recent research has shown that cis-2,3-diphenylcyclopropane-1-carboxylic acid does not undergo ISC on direct irradiation. The reaction encountered is isomerization to the corresponding trans isomer via a 1,3-biradical intermediate. Exothermic bond cleavage is the dominant reaction within radical cations of cyclopropylamines formed by SET to DCA. The photoheterolysis of 9-cyclopropyl-9-fluorenol has been studied in non-acidic zeolites. The rate of formation of the resultant cation is dependent upon the alkali metal counterion. 

A 15-20 2-(2,5-Dimethoxy-4-methylphenyl)-cyclopropylamine S 13 Trans-2-(3,4,5-trimethoxyphenyl)cyclopropylamine S 115 3,4-Dimethoxy-beta-hydroxy-PEA S 100 3,4-Methylenedioxy-beta-hydroxy-PEA... 

Products of the reactions of substituted cyclopropylamines and aziridines with lead(iv) tetra-acetate may be explained by assuming the common intermediacy of a nitrenium ion. The substrate 2-phenylcyclopropylamine (39) reacts to give trans-... 

---