Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Patent
1995-06-07
1997-08-26
Nazario-Gonzalez, Porfirio
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
514421, 514486, 514512, 514513, 514533, 514535, 514538, 514833, 560 30, 560 31, 560 32, 560 42, 562451, 568452, 568455, A61K 31245, A61K 31195, A61K 31325, C07C 4500
Patent
active
056611820
ABSTRACT:
Drug compounds are used as allosteric modifiers of hemoglobin present in red blood cells. The compounds bind to only a single pair of symmetry related sites in the central water cavity of hemoglobin at the Lys 99.alpha., Arg 141.alpha., and Asn 108 .beta. residues. When one of the drug compounds is bound to hemoglobin, it will join three separate sub-units of the hemoglobin molecule and stabilize the hemoglobin in a lower oxygen affinity state. Because the compounds used in this method are either not bound by serum albumin or only interact to small degrees with serum albumin, the compounds are active in whole blood and in vivo. The process of allosterically modifying hemoglobin towards a low oxygen affinity state in whole blood and in vivo could be used in a wide variety of applications including in treatments for ischemia, heart disease, wound healing, Alzheimer's, depression, schizophrenia, adult respiratory distress syndrome (ARDS), etc., in extending the shelf-life of blood or restoring the oxygen carrying capacity of out-dated blood, and as sensitizers for x-ray irradiation in cancer therapy, as well as in many other applications.
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Wei,Enoch P., Randad,Ramnarayan S., Levasseur,Joseph P., Abraham,Donald J., and Kontos,Hermes A. "Effect of local change in O.sub.2 saturation of hemoglobin on cerebral vasodilation from hypoxia and hypotension." American Journal of Physiology 265 (Heart Circulation Physiology 34) H1439-H143, 1993.
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Perutz,Max F., Fermi,Giulio, Abraham,Donald J., Poyart,Claude, and Bursaux,E. "Hemoglobin as a Receptor of Drugs and Peptides: X-ray Studies of the Stereochemistry of Binding." Journal of the American Chemical Society 1986 108:1064.
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Randad,Ramnarayan S., Mahran,Mona A., Mehanna,Ahmed S., Abraham,Donald J. "Allosteric Modifiers of Hemoglobin 1. Desirn, Synthesis, Testing, and Structure--Allosteric Activity Relationship of Novel Hemoglubin Oxygen Affinity Decreasing Agents." Journal of Medicinal Chemistry vol. 34 pp. 752-757 1991.
Abraham,Donald J., Wireko,Fred C., and Randad,Ramnarayan S. "Allosteric Modifiers of Hemoglobin: 2-[4-[[3,5-disubstituted anilino) carbonyl]methyl]pheoxy]-2-methylpropionic Acid Derivatives that Lower the Oxygen Affinity of Hemoglobin in Red Cell Suspensions, in Whole Blood, and in Vivo in Rats." Biochemistry vol. 31, pp. 9141-9149, 1992.
Wireko,Fred C., Kellogg,Glen E., and Abraham,Donald J. "Allosteric Modifiers of Hemoglobin 2. Crystallographiclly Determined Binding Sites and Hydrophobic Binding/Interaction Analysis of Novel Hemoglobin Oxygen Effectors." Journal of Medicinal Chemistry vol. 34, pp.758-767, 1991.
Abraham Donald J.
Poyart Claude
Nazario-Gonzalez Porfirio
Virginia Commonwealth University
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