Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-09-18
1999-07-20
Kight, John
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 45, 536 2722, 536 2761, 536 277, A61K 3170, C07H 19167
Patent
active
059256249
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to therapeutically active 2,6-diaminopurine-.beta.-D-ribofuranuronamide derivatives, processes for the manufacture of said compounds, pharmaceutical formulations containing said compounds and the use of said compounds in chemotherapy. In particular, we have found a group of novel compounds which are effective in treating inflammatory diseases.
Inflammation is a primary response to tissue injury or microbial invasion and is characterised by circulating leukocytes binding to and extravasion through vascular endothelium. Circulating leukocytes include neutrophils, eosinophils, basophils, monocytes and lymphocytes. Different forms of inflammation involve different types of infiltrating leukocytes, the particular profile being regulated by gene expression in vascular endothelium in response to a variety of inflammatory mediators.
The primary function of leukocytes is to defend the host from invading organisms such as bacteria and parasites. Once a tissue is injured or infected a series of events occurs which causes the local recruitment of leukocytes from the circulation into the affected tissue. Leukocyte recruitment is controlled to allow for the orderly destruction and phagocytosis of foreign or dead cells, followed by tissue repair and resolution of the inflammatory infiltrate. However in chronic inflammatory states, recruitment and resolution are not adequately controlled and the inflammatory reaction causes tissue destruction.
We have now found a novel group of compounds with broad anti-inflammatory properties which inhibit leukocyte recruitment and activation. The compounds are therefore of potential therapeutic benefit in providing protection from leukocyte-induced tissue damage in diseases where leukocytes are implicated at the site of inflammation. The compounds of the invention may also represent a safer alternative to corticosteroids in the treatment of inflammatory diseases, whose uses are severely limited by their side-effect profiles.
Thus, according to one aspect of this invention, we provide a compound of general formula (I) ##STR2## and salts and solvates thereof, wherein:
R.sup.1 represents a hydrogen atom or a (C.sub.3-8)cycloalkyl or (C.sub.1-6)alkyl group;
R.sup.2 represents a group selected from 3 groups) which may be the same or different and are selected from C.sub.2-7 acylamino, guanidino, carboxyl, oxo and (CH.sub.2).sub.p R.sup.3 (where p is zero or 1 and R.sup.3 is hydroxy, NH.sub.2, (C.sub.1-6)alkylamino or di(C.sub.1-6)alkylamino) piperidin-3-yl or piperidin-4-yl in which the ring nitrogen atom is substituted by hydrogen, (C.sub.1-6)alkyl or aryl(C.sub.1-6)alkyl (e.g. benzyl) nitrogen atom is substituted by hydrogen, (C.sub.1-6)alkyl or aryl(C.sub.1-6)alkyl (e.g. benzyl) and one or more of the ring carbon atoms (e.g. 1, 2 or 3 ring carbon atoms) is substituted by the same or different groups selected from (C.sub.2-7)acylamino, guanidino, oxo and (CH.sub.2).sub.p R.sup.3 (where p and R.sup.3 are as defined previously) carbon atoms (e.g. 1, 2 or 3 ring carbon atoms) is substituted by the same or different groups selected from (C.sub.2-7)acylamino, guanidino, carboxyl, oxo and (CH.sub.2).sub.p R.sup.3 (where p and R.sup.3 are as defined previously) group selected from (C.sub.2-7)acylamino, guanidino, hydroxyl, NH.sub.2, (C.sub.1-6)alkylamino, di(C.sub.1-6)alkylamino or ##STR3##
(where X is a bond, O, CH.sub.2 or NR.sup.4 in which R.sup.4 is hydrogen, (C.sub.1-6)alkyl or aryl(C.sub.1-6)alkyl) and independently represent zero or 1 except that when m is 1 then n must also represent 1, R.sup.5 is a hydrogen atom or a carboxy group or a group CH.sub.2 R.sup.6 (where R.sup.6 is (C.sub.2-7)acylamino, guanidino, hydroxy, methoxy, NH.sub.2, (C.sub.1-6)alkylamino or di(C.sub.1-6)alkylamino), Alk.sub.2 is a (C.sub.1-5)alkylidene group and Z is a hydrogen atom or an optionally substituted aromatic ring selected from phenyl, pyridyl, pyrimidinyl, imidazolyl, triazolyl, tetrazolyl and benzimidazolyl where the ring is optionally substituted by one or more groups (e.g.
REFERENCES:
patent: 3983104 (1976-09-01), Vorbruggen
patent: 4663313 (1987-05-01), Bristol et al.
patent: 4704381 (1987-11-01), Schaumann et al.
patent: 4757747 (1988-07-01), Hamilton et al.
patent: 4968697 (1990-11-01), Hutchison
patent: 4985409 (1991-01-01), Yamada et al.
patent: 5043325 (1991-08-01), Olsson et al.
patent: 5106837 (1992-04-01), Carson et al.
patent: 5219839 (1993-06-01), Bru-Magniez et al.
patent: 5219840 (1993-06-01), Gadient et al.
patent: 5446139 (1995-08-01), Seela et al.
patent: 5459255 (1995-10-01), Cook et al.
Hutchison et al., Journal of Medicinal Chemistry, vol. 33, No. 7, Jul. 1990, 1919-1924.
Goodman, "Chemical Syntheses and Transformations of Nucleosides," Chapter 2 in Basic Principles in Nucleic Acid Chemistry, vol. 1, P.O.P. Ts'o (ed.), Academic Press, New York, NY, 1974, pp. 94-208, only pp. 94, 154, 159-160 and 203-204 supplied.
Ayres, deceased Barry Edward
Ellis Frank
Ewan George Blanch
Gregson Michael
Knight John
Crane L. Eric
Glaxo Group Limited
Kight John
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