Viscometry tritium cyclosporine and

 

(57) Abstract:

Use: in organic chemistry in biomedical research. The essence of the invention: received new visokomernoe tritium physiologically active compound cyclosporin a of formula I.

The invention relates to the field of organic chemistry and can be used in biomedical research.

Modern methods of investigation of physiologically active compounds require the use of them in the form of wisokomernix derivatives.

Cyclosporine A is a substance of General formula

< / BR>
(The Merck Index an encyclopedia of chemicals druds and biolodicals Eleventth Edition and 12-th 1989-1996 NJ U. S. A.),

is the physiologically active compound. Cyclosporine A is described as vysokobarnogo tritium derived.

The problem solved by the present invention, has been the expansion of the range wisokomernix physiologically active compounds. The problem is solved in that the first received viscometry tritium cyclosporine A.

Below are examples illustrating the invention.

Example 1. The reaction vial was placed to 12.1 mg of cyclosporine A, 30,8 mg 5% PdO/Al2O3, 52,0 mg PdO. Attempted gajoob the oC for 10 minutes At this generated when recovering palladium oxide absolutely tritium water was condensed in the middle of the ampoule. Next, the zone containing the activated catalyst was evacuated at a temperature of 20oC 10 minutes With most of the adsorbed on the catalyst tritium was removed and has not first made a double bond cyclosporine A. Then the reaction was performed as follows. Filmed cooling from the middle part of the ampoule was cooled with liquid nitrogen the lower part of the ampoule. While tritium water was converted into a mixture of catalyst and substances, the ampoule was removed from the installation, in the reaction vials were injected with 100 μl of a mixture of dioxane with triethylamine (9:1), the ampoule was sealed and the reaction was performed at 150oC 60 minutes and Then the contents of the vials were frozen with liquid nitrogen, the ampoule was opened, the catalyst was filtered and washed with methanol (h,5 ml). The total radioactivity of the reaction solution after isotopic exchange of 13.2 Key, without tritium water - 0,7 Ki, after TLC - 140 MCI, after the first HPLC - 45 MCI, after the second HPLC - 8 MCI (radiochemical purity higher than 97%). The output labeled drug 60 - 65%, with molar radioactivity - 1 CI/mmol.

Labeled the product was purified chromatographic methods: TLC: (is; C) benzene-dioxane (4: 1) Rf 0,36; (G) chloroform-dioxane (4:1) Rf Of 0.65; (D) hexane-ISO-propyl alcohol (4:1) Rf of 0.53. HPLC: (W) Saporon SGX, 5 μm, 3,h mm, methanol-50 mm ammoniumphosphate buffer (pH 4.5) (85:15), V - 2 ml, 60oC, hold time - 15,41 min; (And) Silasorb C18, 13 μm, h mm, methanol-water-acetic acid (85:15:0,1), V - 2 ml, 60oC, retention time - 15,85 min; (K) Nucleosil C18, 5 μm, h mm, methanol - 50 mm buffer (pH 2,7) (82:18), V - 0.1 ml/min, 50oC, retention time - 9,05 min; (M) Nucleosil C18, 5 μm, h mm, methanol-buffer (pH 4.5) (87:13), V - 0.1 ml/min, 60oC, retention time - 5,52 minutes

Example 2. In the reaction, the ampoule was placed to 12.4 mg of cyclosporine A, 31 mg of 5% PdO/Al2O3, of 51.7 mg PdO. Was filled with gaseous tritium to a pressure of 450 hPa, and cooled with liquid nitrogen the middle part of the ampoule and the mixture was heated at 70oC for 10 minutes At this generated when recovering palladium oxide absolutely titiev water condensed in the middle of the ampoule. Next, the zone containing the activated catalyst was evacuated at a temperature of 25oC 5 minutes At most of the adsorbed on the catalyst tritium was removed and has not first made a double bond cyclosporine A. Then the reaction was performed as follows. Filmed cooling with the camping catalyst and substances the ampoule was removed from the installation, in the reaction vials were injected with 100 μl of a mixture of dioxane with triethylamine (9:1), the ampoule was sealed and the reaction was performed at 180oC 40 minutes and Then the contents of the vials were frozen with liquid nitrogen, the ampoule was opened, the catalyst was filtered and washed with methanol (g,5 mm). The total radioactivity of the reaction solution after isotopic exchange 13 Key, without tritium water is 0.8 Ki, after TLC - 180 MCI, after the first HPLC - 60 MCI, after the second HPLC - 30 MkI (radiochemical purity higher than 97%). The output labeled drug is 50% to 55%, with molar radioactivity - 4 CI/mmol.

Thus, for the first time received viscometry tritium cyclosporine A.

Viscometry tritium cyclosporine a formula



 

Same patents:

The invention relates to new oligopeptides having affinity to the opiate receptors, which may be linear or cyclic Pentapeptide with the primary sequence of amino acids in the skeletal Tyr-X-Hairdryer-S-Z, where X and Z denote amino acids or derivatives of amino acids and/or analogs, and where X and Z can be covalently linked, form a heterocyclic structure in which Z is selected from Cys, Glu, GLn or derivatives of Glu and GLn; X is selected from amino acids or amino acid analogs, such as Ser, Glu, D-Ala, D - or Z-2,4-diaminobutane acid, AMCC, CIS or their derivatives
The invention relates to new cyclopeptides formula (I): cyclo-(Arg-B-Asp-X-Y), where B, X and Y are specified in paragraph

The invention relates to new compounds of formula I cyclo-(a-b-C-D-Agde), where a-D-Val; (B - L - or D-Phe; C - L-Asp, D-Asp (O-C1-C4-alkyl), D-Gly, or Ala, and at least two of these amino acid residues are in the D-form, and their salts

The invention relates to certain Aza cyclopentapeptide compounds having a nitrogen atom attached to cyclohexadienone ring on the 5th carbon atom of the component 4-hydroxy-ornithine (C-5-orn"), formula I, where R1Is H or OH; R2- H, CH3or OH; R3- H, CH3CH2CN, CH2CH2NH2or CH2CONH2; RI- C9-C21-alkyl, C9-C21alkenyl, C1-C10-alkoxyphenyl or C1-C10alkoxyaryl; RII- H, C1-C4-alkyl, C3-C4alkenyl, (CH2)2-4OH, CO(CH2)1-4NH2, (CH2)2-4NRIVRV; RIIand RIIItaken together, -(CH2)4-, -(CH2)5-, -(CH2)2O(CH2)2-, -(CH2)2NH(CH2)2-; RIV- H or alkyl; RVIs H or alkyl and salt additive

The invention relates to new polypeptide compound and its pharmaceutical acceptable salts

The invention relates to organic chemistry and can find application in biochemistry, medicine, biomedical research

The invention relates to the field of organic chemistry and can find application in biochemistry and medicine

amino acids" target="_blank">

The invention relates to the field of biotechnology and organic chemistry, to methods for isotopentechnik natural compounds, namely: L--amino acids, and may find use in experimental biology, medicine, veterinary science, agriculture

- haloalkyl" target="_blank">

The invention relates to organic chemistry and can find applications in the fields of biology and medicine

The invention relates to a technology for radioactive organic compounds, in particular to methods of introducing a radioactive label in natural compounds, and can be used in research laboratories to study the metabolism and biological activity of chlorophyll and its biotransformation products

The invention relates to the field of organic and biological chemistry and relates to techniques for obtaining tritium-labeled thymine, which can find application in biochemical research and in experimental medicine and veterinary, breeding works

The invention relates to medicine, in particular to Oncology and immunology, and for the treatment of b-cell lymphoma

The invention relates to medicine, in particular to Oncology and immunology, and for the treatment of b-cell lymphoma

The invention relates to pharmaceutical industry and relates to microcapsules
Up!