Bind to integrin peptide and its application

 

The invention relates to cyclic bind to the integrin peptide length 7-11 amino acid residues that includes the amino acid sequence (RKK). Compounds according to the invention are blockers domain2I integrin person, as well as potential inhibitors of integrin interaction of man with collagen types I and IV and laminin-1. Also described pharmaceutical composition containing the described peptide, methods of inhibiting the binding of integrins, cell migration, adhesion of platelets and methods of analysis of binding agents with the integrin. 11 C. and 4 h.p. f-crystals, 10 ill., table 1.

The text descriptions in facsimile(see graphic part).

Claims

1. Cyclic bind to integrin peptide length 7-11 amino acid residues that includes the amino acid sequence of RKK.

2. The peptide under item 1, comprising the amino acid sequence RK (SEQ ID NO 8).

3. Cyclic peptide comprising amino acid sequence X1RKKHX2Xnthat X is any amino acid and n= 1-4.

4. Cyclic communicating with integrity with integrin peptide, comprising the amino acid sequence CTRKKHDNQ (SEQ ID NO 5).

6. Pharmaceutical composition having the ability to contact the domain2I integrin person containing binding with integrin peptide according to any one of paragraphs. 1-5.

7. The pharmaceutical composition according to p. 6, suitable for local use.

8. Method of inhibiting the binding of integrins containing domain2I, with molecules that recognize the specified domain2I, which includes ensuring the interaction of the indicated integrin with the specified binding with integrin peptide according to any one of paragraphs. 1-5.

9. The method of inhibition is dependent on integrin cell migration in a patient, comprising providing specified patient effective amounts of the specified bind to integrin peptide according to any one of paragraphs. 1-5.

10. The method according to p. 8, where the specified migration of cells associated with cancer, cardiovascular disease, or periodontitis in the specified patient.

11. Method of inhibiting cell migration on collagen in a patient in need of such treatment, comprising the introduction of a specified patient effective amounts of Yagami collagen platelet aggregation in a patient, includes the provision of specified patient effective amounts of the specified bind to integrin peptide according to any one of paragraphs. 1-5.

13. The method according to p. 13, where the specified adhesion or aggregation associated with cardiovascular disease in said patient.

14. The method of analysis of binding to be used for identifying binding with integrin agents, including (i) biotinylation bind to integrin agent testing which is carried out, ii) carrying out the reaction of the indicated biotinylated agent with immobilized recombinant domain2I or derived from this domain peptides in a suitable binding conditions, (iii) washing the solid substrate carrying an associated agent, (iv) adding a labeled Biotin-binding agent, and (v) identify any associated integrin-binding agent.

15. The method of analysis of binding to be used for identifying binding with integrin agents, including (i) the tagging domain2I is a europium (ii) a mixture bind to integrin agent, which must be tested, labeled with europium domain2I, p

 

Same patents:

The invention relates to derivatives of cyclic peptides of General formula I cyclo (Arg-X-Asp-R1), where X represents Gly, Ala; R1- the remainder of the formula II

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where R2, R3denote H; R4= R5- Ar or R4= Ar, where R5- alkylen (C1-C6); Ar is unsubstituted phenyl; or R4= A, where A = (C1-C6)alkyl, and, if you have in mind remains optically active amino acids, these compounds include D-and L-forms, and their salts, method of production thereof, pharmaceutical composition having the ability to inhibit integrin containing as active ingredient a compound of the formula I

The invention relates to cyclopeptides formula I: SUSE-(Arg-Gly-Asp-X-Y) (I), where X is Phe, Homo-Phe, Phg, Phe(4-F) or Phe (4-Cl), Y means hPro, Ahds, Aos, Nhdg, Acha, Aib, ASRA or Тle, and in the case of residues of optically active amino acids and derivatives of amino acids (D - and L-forms, as well as derivatives, especially-ester of aspartic acid or N-quandialla derivatives of arginine, prodrugs and their physiologically acceptable salts

The invention relates to a method for cyclosporine And high purity by purification of the crude product containing cyclosporiasis complex by multi-step chromatography on silica gel at high load columns from 10 to 52%, using as eluent a mixture of toluene with acetone in an amount of from 10 to 30 vol.% or toluene with ethyl acetate in an amount of from 10 to 35 vol.%, cyclosporine And high purity with content cyclosporine L, U and D less than 0.05% and the content of cyclosporine and < 0,02% vol., industrial method of purification of cyclosporin a from a crude product containing complex cyclosporiasis

The invention relates to compounds of the formula I

R1-Q1-X-Q2-R2(I)

in which Q1, Q2in each case, independently of one another are either absent or represent-NH-(CH2)n-CO-,

R1, R2in each case, independently of each other either absent or represent a cyclo-(Arg-Gly-Asp-Z), where Z is linked to the side chain of Q1or Q2or, if Q1and/or Q2missing (et), with X and where at least one of the radicals R1or R2must always be present,

X represents a-CO-R18-CO-, and if R1-Q1or R2-Q2- no, there is an R10, R13, R16, Het-CO -, or the residue of a fluorescent dye that is chemically linked through CONH-, -COO-, -NH-C(=S)-NH- -NH-C(=O)-NH-, - SO2NH -, or-NHCO-bonds

Z in each case independently represents an amino acid residue or di-, tri - or tetrapeptides balance, where amino acids independently selected from the group comprising Ala, Asn, Asp, Arg, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val or M

where these amino acids can be derived and amino acid residues connected to one another like xilinix groups, and where M is always present,

M represents NH(R8)-CH(R3)COOH,

R3- R5-R4, -R6-R4or-R7-R4< / BR>
R4is a HE, NH2, SH or COOH,

R5- alkylene containing 1-6 carbon atoms,

R6- alkaliphiles containing 7 to 14 carbon atoms,

R7- alkylenediamine containing 8-15 carbon atoms,

R8-H, a or alkylether containing 7-12 carbon atoms,

A is alkyl containing 1-6 carbon atoms,

R10- alkanoyl containing 1-18 carbon atoms, which is unsubstituted or contains one Deputy from among COOH, COOA, SR11or NR12R12,

R11- H or trityl, pyridyl-2-thio - or allylthiourea containing 1-6 carbon atoms,

R12, R12'each, independently of one another, represent H, alkyl containing 1-8 carbon atoms or a protective group of amino group,

R13- aroyl, which contains 7 to 11 carbon atoms and is unsubstituted or substituted and contains one or two substituent selected from the group comprising alkyl containing 1-6 carbon atoms, alkoxygroup containing 1-4 carbon atoms, alkanoyl containing 1-8 tomsche independently of one another H or A,

R16is arkanoid, which contains 7-19 carbon atoms and which is not substituted or substituted in the aryl fragment of one, two or three deputies, including Hal, alkoxygroup containing 1-6 carbon atoms, or HE, and in which the aryl fragment may also represent a group:

< / BR>
E - CH2or,

D is carbonyl or [C(R17R17')]m,

R17R17'each independently represents H or A,

R18is absent or is an R19, R20, R19-R20-R19or phenylene, which is not substituted or substituted and contains one or two substituent R5the length of the chain which is in each case independently of each other,

R19is alkylene containing 1-8 carbon atoms, where 1 or 2 methylene groups can be replaced with S, -CH=CH - or,

R20- cycloalkyl containing 3-7 carbon atoms,

Hal is F, Cl, Br or I,

Het is a monocyclic or bicyclic saturated, unsaturated or aromatic heterocycle which contains from 1 to 4 atoms of N, O and/or S, attached cherepy, including Hal, A, R3, NR4R4', CN, NO2and/or carbonyl oxygen,

n- 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 and

m is 1 or 2,

where, assuming that residues are residues of optically active amino acids and derivatives of amino acids, contain both D and L forms, and their salts

Cyclopeptide // 2171260
The invention relates to cyclopeptides and to their therapeutic use as inhibitors of the expression of adhesion molecules

The invention relates to new methods of chromatography, designed for the purification of crude extracts containing cyclosporine, for use in the pharmaceutical industry

The invention relates to a new group of individual chemical compounds - cyclic amino compounds represented by the following formula:

< / BR>
where R1represents a phenyl group which may be optionally substituted by at least one Deputy, which represents a halogen atom; R2represents a C1-C8aliphatic acyl group or (C1-C4alkoxy) carbonyl group; and R3represents a saturated cyclic amino group which has from 2 to 8 carbon atoms in one or more cycles, with the highest nitrogen cycle has from 3 to 7 atoms in the cycle, and the specified saturated cyclic amino group substituted by a group having the formula-S-S-R4where R4and X have the meanings as defined below, and the said saturated cyclic amino group attached via its cyclic nitrogen atom adjacent to the carbon atom that is attached to the substituents R2and R1; R4represents a phenyl group which may be optionally substituted by at least one Deputy, selected IGP and nitro groups; WITH1-C6alkyl group which may be optionally substituted by at least one Deputy, selected from the group consisting of amino groups, carboxyl groups, (C1-C4alkoxy)carbonyl groups, substituents having the formula-NH-A1(where a1represents an-amino acid residue), and substituents having the formula-CO-AND2(where a2represents an-amino acid residue); or (C3-C8cycloalkyl group, and X represents a sulfur atom, sulfinol group or sulfonyloxy group, and the above-mentioned cyclic aminecontaining group may be optionally additionally substituted by a group having the formula = CR5R6where R5and R6are the same or different, and each independently represents a hydrogen atom, a carboxyl group, (C1-C4alkoxy)carbonyl group, karbamoilnuyu group, (C1-C4alkyl) karbamoilnuyu group or di-(C1-C4alkyl)karbamoilnuyu group; or their pharmacologically acceptable salts, pharmaceutical composition having inhibitory action in Rel is the prevention of disease, selected from the group consisting of embolism and thrombosis in a warm-blooded animal

The invention relates to derivatives of cyclic peptides of General formula I cyclo (Arg-X-Asp-R1), where X represents Gly, Ala; R1- the remainder of the formula II

< / BR>
where R2, R3denote H; R4= R5- Ar or R4= Ar, where R5- alkylen (C1-C6); Ar is unsubstituted phenyl; or R4= A, where A = (C1-C6)alkyl, and, if you have in mind remains optically active amino acids, these compounds include D-and L-forms, and their salts, method of production thereof, pharmaceutical composition having the ability to inhibit integrin containing as active ingredient a compound of the formula I

-converting enzyme)" target="_blank">

The invention relates to novel ortho-sulfonamidophenylhydrazine heteroaryl hydroxamic acids of the formula

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where W and X are both carbon, T is nitrogen, U represents CR1where R1represents hydrogen, or alkyl containing 1-8 carbon atoms, R represents-N(CH2R5)-SO2Z, Q represents -(C=O)-NHOH, with

< / BR>
is a benzene ring, or is a heteroaryl ring of 5 to 6 atoms in the cycle, which may contain 0-2 heteroatoms selected from nitrogen, oxygen and sulfur, in addition to the heteroatom of nitrogen, denoted as W, where benzene or heteroaryl ring may optionally contain one or two substituent R1where permissible; Z is phenyl, which is optionally substituted by phenyl, alkyl with 1-8 carbon atoms, or a group OR2; R1represents halogen, alkyl with 1-8 carbon atoms, alkenyl with 2-6 carbon atoms, perfluoroalkyl from 1 to 4 carbon atoms, phenyl, optionally substituted by 1-2 groups OR2group-NO2group -(CH2)nZ, where Z is a phenyl which allows an alkyl with 1-8 carbon atoms, phenyl, optionally substituted with halogen, or heteroaryl radical containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; R5represents hydrogen, alkyl with 1-8 carbon atoms, phenyl, or heteroaryl containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; or their pharmaceutically acceptable salts

The invention relates to derivatives of N-(4-carbamimidoyl) glycinamide formula (I), where E denotes hydrogen or HE, Q denotes hydrogen or alkyl, R is aryl, cycloalkyl or alkyl substituted radicals R1, R2, R3, R1denotes hydrogen, COOH, COO-alkyl or aryl, R2denotes hydrogen, aryl, cycloalkyl or heteroaryl, R3denotes hydrogen, aryl or HE (in any position other thanposition relative to the nitrogen atom is attached to an alkyl group R) or optional substituted by an amino group, three of the radicals X1-X4denote the group of C(Ra), C(Rb) or C(Rc), and the fourth represents C(Rd), Ra-Rddenote H, HE, NO2dialkylamino, halogen, alkyl, alkoxy, aryloxy, aralkylated, heteroarylboronic, geterotsiklicheskikh, COOH, COO-alkyl, NH-SO2-alkyl, NH-SO2-aryl, two adjacent groups Ra-Rbdenote alkylenedioxy, G1and G2denote hydrogen, HE, the invention relates to intermediate compounds of the formula (IV), (V), (VI) used in the methods of making compounds of formula (I), and are in взаимодействCN, the nitrile of formula (IV) is transformed into amidinopropane C(N-G1)NH-G2

The invention relates to chemical-pharmaceutical industry, associated with obtaining water-soluble drugs acetylsalicylic acid (ASA) related to non-steroidal anti-inflammatory drugs and possessing antithrombotic, analgesic, anti-inflammatory and antipyretic action, the main of which is the influence on the adhesion and aggregation of platelets [Bokarev, I. N., A. Ivlev I

The invention relates to new compounds of General formula I

< / BR>
where a is Gly; the remainder of the formula II

< / BR>
m= 0 or 1; n= 2 or 3; R1and R2each independently of the other represents H, R1and R2both together represent also

< / BR>
or

< / BR>
where IS -(CO)-(CH2)q-(CO)rwhere q=1, 2, or 3, r=0 or 1, or-CO-CH=CH-CO-; X IS H, Cl or1-C6alkyl; and if the mean remains optically active amino acids and derivatives of amino acids, are included as D-and L-forms, and their salts, process for the preparation of compounds of formula I and their salts; pharmaceutical composition having the ability to inhibit integrin containing in its structure at least one compound of the formula I and/or one of its physiologically acceptable salts

The invention relates to the field of organic chemistry, namely to new bicikliski derived pyrimidine

The invention relates to new compounds of the formula (I), where R1is hydrogen or a fragment of ester, E is hydrogen or hydroxy, three of X1-X4denote the group of C(Ra), C(Rb) or C(Rc), and the fourth represents C(Rdor N, where Ra-Rdis hydrogen, alkenyl, quinil, alkenylacyl, alkoxy, alkylamino, alkoxyalkyl, alkoxyalkanols, alkoxycarbonylmethyl, alkoxycarbonylmethyl, alkoxycarbonylmethyl, alkyl, alkoxycarbonylmethyl, alkylsulfanyl, alkylsulfonyl, alkylsulfonyl, allylurea, allylthiourea, alkylsulfonamides, alkylsulfonyl, aminoethoxy, arylalkyl, Allakaket, arylalkyl, arylalkylamine, arylcarboxylic, arylcarboxamide, aryloxy, aryloxyalkyl, arylsulfonyl, arylsulfonamides, carboxy, carboxylic, substituted alkyl, substituted amino, halogen, substituted halogen, cycloalkyl, substituted cycloalkyl, hydroxy, substituted hydroxy, heterocycle, substituted heterocycle, or two adjacent groups of Ra-Rdtogether form the fragment condensed di - or monooxygenase ring or aryl ring

The invention relates to a derivative of biphenylamine General formula (1), where R1represents a hydrogen atom; L represents a direct bond or C1-4-alkylenes group; R2represents a carboxyl group;1-8-alkoxycarbonyl group; karbamoilnuyu group, and a nitrogen atom that is part of carbamoyl group, may be substituted mono - or di-C1-8is an alkyl group or may be a nitrogen atom in the amino acid; C1-8-alkylcarboxylic group; R3represents a hydrogen atom; X represents any of the groups-O-, -NH-CO-NH-, -N(R4)-, -CO-N(R5)-, -N(R5)-CO-, in which R4represents a hydrogen atom, a C1-10is an alkyl group, a C1-10-alkylcarboxylic group1-10-alkylsulfonyl group, R5represents a hydrogen atom, a C1-10is an alkyl group, Y represents a C4-8-cycloalkyl the group in which the methylene group in the C4-8-cycloalkyl may be substituted WITH1-8is an alkyl group WITH1-8-CNS group, carbamoyl group1-8-alkoxycarbonyl group, a carboxyl group, or the following 5-8-membered ring of formula I-1

The invention relates to derivatives of cyclic peptides of General formula I cyclo (Arg-X-Asp-R1), where X represents Gly, Ala; R1- the remainder of the formula II

< / BR>
where R2, R3denote H; R4= R5- Ar or R4= Ar, where R5- alkylen (C1-C6); Ar is unsubstituted phenyl; or R4= A, where A = (C1-C6)alkyl, and, if you have in mind remains optically active amino acids, these compounds include D-and L-forms, and their salts, method of production thereof, pharmaceutical composition having the ability to inhibit integrin containing as active ingredient a compound of the formula I
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