Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1998-06-05
1999-10-26
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540461, 530317, A61K 3147, C07D48704, C07D24100
Patent
active
059729260
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel pyridine or pyrazine compounds and their use in the regulation of haematopoiesis, in particular in the stimulation of haematopoiesis, and in the treatment of bacterial, viral and fungal diseases.
The mammalian body contains cells having enormously diverse structures and functions, and the mechanisms of differentiation and development have been the focus of much study. It is known that for systems of cells having a continuous turnover the mechanism commonly involves a reservoir of pluripotent stem cells which divide and constantly supply new cells to the system. While initially homogeneous the stem cells supplied from the "reservoir" soon become committed to one or other morphology and subsequently develop into the required functional cells.
One example of such a stem cell system is the haemopoietic system in bone marrow.
The manipulation or control of stem cell division is of great potential therapeutically and much research continues to be devoted to elucidating the mechanisms involved and the chemical messengers responsible. To date several biomolecules have been identified as possessing a role in cell production and differentiation either by the stimulation or inhibition of a step within the process. Myelopoiesis has been particularly well studied in this regard and molecules involved in its control include: colony-stimulating factors (CSF) such as granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), multi-lineage colony-stimulating factor (multi-CSF; IL-3) [see Metcalf, Science 229: 16 (1985)], interleukin II (IL-II) [see Paul et al Proc Natl Acad Sci USA 87: 7521 (1990)], Lactoferrin [see Broxmeyer et al Blood Cells 11: 429 (1986)], prostaglandins [see Pelus et al J. Immuno 140: 479 (1988)], acidic (H-subunit) ferritin [see Broxmeyer et al Blood 68: 1257 (1986)], inferferons (.alpha., .beta. and .gamma.) [see Pelus et al supra. and Broxmeyer et al J. Immuno 131: 1300 (1983)], tumour necosis factors (.alpha. and .beta.) [see Broxmeyer et al J Immunol 136: 4487 (1986)], transforming growth factor-.beta. [see Ottman et al J Immunol 140: 2661 (1988)], and activin and inhibin [see Broxmeyer et al Proc Natl Acad Sci USA 86: 779 (1989)].
It has also been found that the haemoregulatory pentapeptide (pEEDCK) inhibits the proliferation of myelopoietic cells selectively [see Paukovits et al Z. Naturforsch 37: 1297 (1982)] and other peptides corresponding to a narrow general formula have been found to exert a similar inhibitor effect in hemopoiesis [see EP-A-112656 and WO90/02753]. Oxidation of the peptide monomers results in dimeric molecules linked by a cysteine bridge and these dimeric molecules have also been found to stimulate myelopoiesis [see Laerum et al. Exp. Hematol 16: 274 (1988)]. The (pEEDCK).sub.2 dimer and other similar compounds are disclosed in WO-A-88/03535.
There is however a continuing need for compounds capable of regulating cell proliferation, in particular haematopoiesis, to a useful level in vivo. In this regard it should be noted that selective stimulation of individual cell types is of particular clinical importance.
The present invention relates to certain novel pyridine and pyrazine-containing compounds capable of regulating, in particular stimulating, haematopoiesis. Viewed from one aspect the invention provides compounds of formula I: ##STR1## R.sup.1 represents a group ##STR2## one of R.sup.2, R.sup.3 and R.sup.4 represents a group as defined above for R.sup.1 which may be the same as or different from R.sup.1 and the remaining two of R.sup.2, R.sup.3 and R.sup.4 independently represent a hydrogen atom or a C.sub.1 -alkyl group; and R.sup.4 independently represent hydrogen or a C.sub.1 -alkyl group; an aromatic ring and R.sup.1 and R.sup.2 are both ##STR3## Z represents --N-- or --CH--; A represents --CO-- or --CH.sub.2 --; ##STR4## in which X represents --O--, --S--, --NH-- or --CH.sub.2 --; D represents a group --CRSR.sup.6 R.sup.7 or --CR.sup.8
REFERENCES:
Wang et al., J. Med. Chem., vol. 35, No. 15, 1992, pp. 2890-2896.
Cuthbertson Alan
Fischer Peter
Hartmann Michael
Hiebl Johann
Husbyn Mette
Nycomed Imaging AS
Shah Mukund J.
Sripada Pavanaram K
LandOfFree
Pyrazine fused to a cyclic peptide does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pyrazine fused to a cyclic peptide, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pyrazine fused to a cyclic peptide will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-764756