4-Aminomethylcyclohexanecarboxylic Acid Research Articles

Crystal Structure and Properties of N6/AMCC Copolymer from Theory and Fiber XRD

The MSXX force field developed previously from ab initio quantum calculations for studies of nylon are used to study the crystal structure and properties of the copolymer of nylon 6 with AMCC (4-aminomethylcyclohexanecarboxylic acid). For the isolated chain conformation of the copolymer, we consider both axial and equatorial connections of the chain with the cyclohexane ring and find that the best is chair-ee-St, which has equatorial connections on both ends of chair cyclohexane. We consider 12 possible crystal structures for the copolymer (the best four conformations of the isolated chain with the three forms of packing these chains: α form, γ form, and δ form). With 12.5% of AMCC in the copolymer, we find that the γ form with the chair-ee-St chain structure is the most stable, even though the α form is most stable for nylon 6. The calculated X-ray diffraction patterns of the predicted crystal structure fit both equatorial and meridional scans of XRD very well. There are two reasons that make α form less stable for the copolymer. One is the bad contact between the axial hydrogen atoms of the cyclohexane ring and the CH2 hydrogens. The other is the difficulty of intramolecular H-bonds in the copolymer. The predicted chain-axis repeat distance of the copolymer (0 K) is 1.4 A smaller than for the α form of Nylon 6, in good agreement with the X-ray results, which indicates that it is 1.5 A smaller (at 300 K). Young's modulus in the chain direction is calculated to be 93 GPa for the copolymer (at 0 K), which compares to 135 and 295 GPa predicted for γ form and α form nylon 6, respectively. The introduced cyclohexane ring locates between the two amide pockets of the adjacent hydrogen bond sheets and has two major effects on the properties of the copolymer: (i) It causes twisted conformations, which decreases Young's modulus of the copolymer in chain direction. (ii) It makes the chain rigid, which likely is responsible for the decrease in sensitivity of the copolymer to moisture.

肌荒れの発生機序と有効成分の開発に関する研究

With the purpose of clarifying the role of internal factors in the process of dry skin occurs, dry skin was induced experimentally by an ionic surfactant and, using the model system, we investiglated from a pharmacological perspective as a new experimental plan. Through this research, we have conceived a new theory explaining how dry skin occurs. Furthermore, on the beais of this theory, we have developed a new effective compound for its treatment.In order to study on the mechanism by which dry skin occurs, we used anti-inflammatory agents and inhibitors against histological impairment mediators, as well as various substances that were considered to regulate the function of epidermal cells. The results strongly suggested that the occurence of dry skin involves a cause bringing about the over-manifestation of the epidermal plasminogen (PLG) activation system, which in turn causes abnormalities in the regulating mechanisms for the proliferation and differentiation of epidermal cells, and these result in dry skin.We discovered 4-aminomethylcyclohexanecarboxylic acid (t-AMCHA), which was the most effective substance in view of the theory on the occurrence of dry skin. Then we investigated in detail the efficacy of t-AMCHA. The results of our studies confirmed that t-AMCHA strongly suppresses the over-manifestatation of the PLG activation system in the epidermis when dry skin was occurring. In addition, t-AMCHA demonstrated superb effectiveness against phenomena caused by dry skin, including the loss of moisture from the horny layer, the increase in transepidermal water loss (TEWL), accelerated turnover in the horny layer, and the changes in various other indicators such as epidermal hypertrophy.We also performed a double-blind trial on a preparation containing t-AMCHA. Results demonstrated that the preparation containing t-AMCHA definitely made better and faster improvement than the preparation without t-AMCHA in skin surface texture. Furthermore, the t-AMCHA containing preparation showed superior stability and safety and had excellent usability.We demonstrated for the first time that the intraepidermal PLG activation system plays a major role in the process by which dry skin occurs, and founded a new theory on the occurrence of dry skin. In addition, on the basis of this theory, we discovered the effective substance t-AMCHA and conducted research on its practical application. As a result, we have not only verified the theory but also developed a revolutionary new effective substance for cosmetics.

Studies on the enzyme immunoassay of bio-active constituents contained in oriental medicinal drugs. V. Preparation of bovine serum albumin conjugate and .BETA.-galactosidase labelled antigen for enzyme immunoassay of 3.BETA.-(monoglucuron-1'.BETA.-yl)-18.BETA.-glycyrrhetic acid.

In order to prepare an immunogen for enzyme immunoassay of 3 beta-(monoglucuron-1'-beta-yl)-18 beta-glycyrrhetic acid (3MGA), which was isolated from a patient with glycyrrhizin-induced pseudoaldosteronisms, benzyl glycyrrhetate (3) was allowed to react with an acetobromosugar (2) in the presence of silver carbonate to give benzyl 3 beta-(methyl 2',3',4'-triacetyl-glucuron-1' beta-yl)-glycyrrhetate (5) and methyl 3',4'-diacetyl-alpha-1',2'-O-[1-(benzyl glycyrrhet-3 beta-yl)- ethylidene]-D-glucuronate (4). On the other hand, this reaction was carried out in the presence of mercuric cyanide in nitromethane to give compound 5, benzyl 3 beta-acetyl glycyrrhetate (6) and benzyl 11-oxo-A-neooleana-3(5),12-dien-3-oate (7). 4-Aminomethylcyclohexanecarboxylic acid and glycine were introduced as chemical bridges at C-30 of 3 beta-(tert-butylglucuron-1' beta-yl)-glycyrrhetic acid (11) derived from compound 5. The former bridge was used to prepare an immunogenic conjugate with bovine serum albumin, and the latter bridge was used for antigen labelled with beta-galactosidase.

ChemInform Abstract: MEDICINAL CHEMICAL STUDIES ON ANTIPLASMIN DRUGS. V. 4‐AMINOMETHYLCYCLOHEXANECARBOXYLIC ACID DERIVATIVES HAVING A METHYL GROUP AT C2 OR C3

AbstractAuf dem im Formelschema angegebenen Weg werden die Aminomethyl‐methylcyclohexancarbonsäuren (III), (IV), (IX) und (X) hergestellt.

Medicinal chemical studies on antiplasmin drugs. VIII. 4-Aminomethylcyclohexanecarboxylic acid derivatives having a carboxyl or carboxymethyl group at C2.

Four isomers of 4-aminomethyl-1, 2-cyclohexanedicarboxylic acid (4) were synthesized from dimethyl 4-cyanophthalate (2) via 4-aminomethylphthalic acid (3), and the isomers of 4-aminomethyl-2-carboxymethylcyclohexanecarboxylic acid (14) were also synthesized from 5-aminophthalide (10). The configurations and preferred conformations in aqueous solution of the former isomers were determined on the basis of the nuclear magnetic resonance spectra and by converting the compounds to trimethyl 1, 2, 4-cyclohexanetricarboxylates (5), which were compared with 5 obtained from methyl bicyclo [2. 2. 2]-5-octene-2-carboxylate (8), trimethyl trimellitate (6), and trimellitic acid (9). Those of the latter isomers were deduced from the nuclear magnetic resonance spectra snd the relationships of the isomerization products of 14. The compound t-4-aminomethyl-r-1, c-2-cyclohexanedicarboxylic acid (4C), which is thought to exist in the 1-e, 2-a, 4-e form in aqueous solution, showed more potent antiplasmin activity than trans-4-aminomethyl-cyclohexanecarboxylic acid (1A).

Medicinal chemical studies on antiplasmin drugs. V. 4-Aminomethylcyclohexanecarboxylic acid derivatives having a methyl group at C2 or C3.

Four isomers of 4-aminomethyl-2-methylcyclohexanecarboxylic acid (9) were synthesized from 4-cyano-o-toluic acid (2) or cis or trans 2-methyl-4-oxocyclohexanecarboxylic acid (5), and the isomers of 4-aminomethyl-3-methylcyclohexanecarboxylic acid (23) were also synthesized from 4-cyano-m-toluic acid (13) or ethyl cis or trans 7-methyl-1, 4-dioxaspiro [4. 5] decane-8-carboxylate (15). The configurations of these isomers were determined on the basis of those of the starting materials and by leading them to dimethyl 2-methylcyclohexane-1, 4-dicarboxylate (12), which was compared with 12 obtained from 5-methylbicyclo [2. 2. 2] oct-2-ene (10). The preferred conformations of the isomers in aqueous solution were deduced from the nuclear magnetic resonance spectra. The antiplasmin activity of t-4-aminomethyl-c-3-methyl-r-1-cyclohexanecarboxylic acid (23B), which is thought to exist in the 1-e, 3-e, 4-e form in aqueous solution, and which was the most active among the compounds tested in this study, was only about 0.64 times that of trans 4-aminomethylcyclohexanecarboxylic acid (1B).

Medicinal chemical studies on antiplasmin drugs. III. 4-Aminomethylcyclohexanecarboxylic acid and its derivatives having a methyl group.

Medicinal chemical studies on antiplasmin drugs. III. 4-Aminomethylcyclohexanecarboxylic acid and its derivatives having a methyl group.

Complete mass spectra of the per-trimethylsilylated amino acids

The complete mass spectra of the trimethylsilyl derivatives of 46 amino acids are presented. The spectra are discussed in terms of the common fragmentation pathways and factors controlling the fragment formation. The aliphatic α-amino acids are characterized by a molecular ion, M—15 (CH 3), M—43 (CH 3 + CO), M—117 (CO 2TMS), and M—R. The β-amino acids are characterized by a more intense molecular ion, M—15, M—43, a small M—117, and presence of other functional groups results in more complex spectra. In sulfur amino acids, additional fragments were observed for CS and SS bond cleavage with charge retention on both fragments. For serine and threonine, hydroxyl groups caused more prominent cleavage of M—R than would otherwise be expected. Additional amino groups result in β-cleavage to this functional group. Aromatic substitution on the α-carbon results in the additional fragment R. The spectra for 4-aminobutyric acid, and 4-aminomethylcyclohexane carboxylic acid are presented. These amino acids are characterized by a molecular ion, M—15, M—117, and β-cleavage to the amino group. The trimethylsilyl derivative of arginine was found to be identical with that of ornithine. This transformation was shown to occur during the trimethylsilylation step. The trimethylsilyl derivatives are particularly known for their multiple derivative formation. For amino acids, the multiple derivative formation is controlled by the steric hindrance of the amino group within the molecule.

Medicinal chemical studies on antiplasmin drugs. II. Separation of stereoisomers of 4-aminomethylcyclohexanecarboxylic acid and assignment of their configuration.

Medicinal chemical studies on antiplasmin drugs. II. Separation of stereoisomers of 4-aminomethylcyclohexanecarboxylic acid and assignment of their configuration.

Medicinal chemical studies on antiplasmin drugs. I. Establishment of the screening assay method for antiplasmin drugs and the superiority of trans-4-aminomethylcyclohexanecarboxylic acid (tranexamic acid) to cis-form.

The new caseinolytic assay method for antiplasmin activity of synthetic compounds was established by introducing the determination of ID50. trans-Form isomer of 4-aminomethylcyclohexanecarboxylic acid (tranexamic acid) was shown to have very potent antiplasmin activity whereas the cis-form isomer was little effective. The antiplasmin activity of tranexamic acid was 5-7 times greater than that of ε-aminocaproic acid.