Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1999-05-06
2000-05-16
Seaman, D. Margaret
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546177, 546178, C07D21516, A61K 3147
Patent
active
060637919
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to novel compounds derived from N-(benzenesulfonyl)-(L)-proline, to the process for their preparation and to their use in therapeutics.
These novel compounds have an antagonistic action towards bradykinin and are useful in therapeutics, particularly for the treatment of pain and inflammation and especially for the treatment of asthma, cerebral traumatic shock and allergic rhinitis.
PRIOR ART
It is known that one of the possible treatments for certain pathological conditions of a painful and/or inflammatory nature (such as asthma, rhinitis, septic shock, toothache, etc.) is to inhibit the action of certain hormones such as bradykinin or kallidin. These peptide hormones are in fact involved in a large number of physiological processes, some of which are closely associated with these pathological conditions.
Although no product possessing this mode of action has yet been marketed, numerous studies have been undertaken in order to understand the mode of action of kinins, particularly bradykinin and its homologs, and then to create compounds capable of antagonizing the bradykinin receptors. Pharmacological Reviews vol. 44 no. 1, pages 1-80 (1992) and Biopolymers (Peptide Science) vol. 37, pages 143-155 (1995) may be cited among the numerous publications reporting this work.
Bradykinin is a peptide hormone consisting of 9 amino acids (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) and kallidin is a peptide hormone (Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) which contains an additional amino acid (Lys) compared with bradykinin. It is known that earlier studies made it possible to obtain peptides which interact with the bradykinin receptors: some of them, like bradycor (CP.0127 from CORTECH), icatibant (HOE 140 from HOECHST) ["bradycor" and "icatibant" are international non-proprietary names (INN)] or NPC 17761 (from SCIOS-NOVA), have an inhibitory action on the binding of bradykinin to its B.sub.2 receptor. More recently, non-peptide compounds have been proposed as antagonists towards the binding of bradykinin to its B.sub.2 receptor, especially in EP-A-0596406 and EP-A-0622361. It is also known that certain compounds which are structurally related to the compounds referred to in the two patent applications cited above have already been described for their possible antithrombotic properties, especially in the publications DE-A-3617183 and EP-A-0261539.
OBJECT OF THE INVENTION
There is a need for reducing or eliminating pain and inflammation in mammals and particularly in man.
To meet this need, a novel technical solution has been sought which is effective in the treatment of pain, irrespective of its origin, and especially in the treatment of (i) pain associated with inflammatory phenomena, and (ii) inflammation.
According to the invention, it is proposed to provide a novel technical solution which involves competitive binding, at the bradykinin B.sub.2 receptor, between (i) bradykinin and related or analogous hormones, and (ii) an antagonist, and utilizes compounds of the benzenesulfonamide type which are structurally different from the known products mentioned above and which are capable of limiting or substantially inhibiting the binding of bradykinin and analogous hormones to said bradykinin B.sub.2 receptor.
According to this technical solution, the novel compounds bind competitively to the bradykinin B.sub.2 receptor without causing the effects of bradykinin on this receptor (the substance is said to be an antagonist). This results in the appearance of a state analogous to that observed in the absence of bradykinin, namely a reduction in pain and inflammatory reactions.
According to this novel technical solution, it is proposed according to a first aspect of the invention to provide compounds derived from N-(benzenesulfonyl)-(L)-proline as novel industrial products, according to a second aspect of the invention to provide a process for the preparation of these compounds, and according to a third aspect of the invention to provide the use of these compounds, e
REFERENCES:
K.D. Bhoola et al., "Bioregulation of Kinins: Kallikreins, Kininogens, and Kininases," Pharmacological Reviews, vol. 44, No. 1, 1992, pp. 1-80.
John M. Stewart, "Bradykinin Antagonists: Development and Applications," Biopolymers (Peptide Science), vol. 37, 1995, pp. 143-155.
Barth Martine
Bondoux Michel
Dodey Pierre
Houziaux Patrick
Ou Khan
Fournier Industrie et Sante
Seaman D. Margaret
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