Methods of synthesis for 9-substituted hypoxanthine derivatives

Details Methods of synthesis for 9-substituted hypoxanthine derivatives Methods of synthesis for 9-substituted hypoxanthine derivatives

2005-02-01

2005-02-01

Berch, Mark L (Department: 1624)

Organic compounds -- part of the class 532-570 series

Organic compounds

Chalcogen bonded directly to ring carbon of the purine ring...

C548S326500

Reexamination Certificate

active

06849735

ABSTRACT:
An improved method of synthesis of a 9-substituted hypoxanthine derivative comprises the steps of: (1) reacting aminocyanacetamide with triethyl orthoformate to form an imidoester derivative of aminocyanacetamide; (2) forming a compound having a reactive amino group on a hydrocarbyl moiety, the hydrocarbyl moiety being linked through an amide group to a physiologically active moiety or an esterified derivative of a physiologically active moiety including therein an esterified benzoyl group; (3) reacting the imidoester with the compound having the reactive amino group on the hydrocarbyl moiety to form a derivative of aminoimidazole-4-carboxamide substituted at the 1-position with a hydrocarbyl moiety linked through an amide group to a physiologically active moiety including therein an optionally esterified benzoyl group; (4) forming the six-membered heterocyclic ring of the purine moiety of the hypoxanthine by reacting the derivative of 5-aminoimidazole-4-carboxamide formed in step (3) with triethyl orthoformate to form a 9-substituted hypoxanthine compound substituted at the 9-position with a hydrocarbyl moiety linked through an amide group to a physiologically active moiety including therein an optionally esterified benzoyl group; and (5) hydrolyzing the ester of the optionally esterified benzoyl group if present.

REFERENCES:
patent: 3300380 (1967-01-01), Gray et al.
patent: 3321369 (1967-05-01), Glasky et al.
patent: 3438968 (1969-04-01), Glasky et al.
patent: 3666856 (1972-05-01), Elion et al.
patent: 4035486 (1977-07-01), Laborit
patent: 4138562 (1979-02-01), Vince
patent: 4221794 (1980-09-01), Simon et al.
patent: 4221909 (1980-09-01), Simon et al.
patent: 4221910 (1980-09-01), Giner-Sorolla
patent: 4315920 (1982-02-01), Schaeffer et al.
patent: 4340726 (1982-07-01), Simon et al.
patent: 4347360 (1982-08-01), Ogilvie
patent: 4451478 (1984-05-01), Simon et al.
patent: 4643992 (1987-02-01), Goodman et al.
patent: 4914028 (1990-04-01), Hertel
patent: 4952693 (1990-08-01), Sircar et al.
patent: 4983494 (1991-01-01), Kitaguchi
patent: 5023294 (1991-06-01), Goto et al.
patent: 5091432 (1992-02-01), Glasky
patent: 5093318 (1992-03-01), Goodman et al.
patent: 5187162 (1993-02-01), Marangos et al.
patent: 5192749 (1993-03-01), O-Yang
patent: 5237051 (1993-08-01), Garbers et al.
patent: 5256677 (1993-10-01), Sham et al.
patent: 5376642 (1994-12-01), Yarchoan et al.
patent: 5447936 (1995-09-01), Glasky
patent: 5565437 (1996-10-01), Marquez et al.
patent: 5595901 (1997-01-01), Rocancourt et al.
patent: 5795756 (1998-08-01), Johnson et al.
patent: 5801159 (1998-09-01), Miller et al.
patent: 5801184 (1998-09-01), Glasky
patent: 5861532 (1999-01-01), Brown
patent: 5948771 (1999-09-01), Danziger
patent: 6027936 (2000-02-01), Glasky
patent: 0924195 (1999-06-01), None
patent: WP 9956550 (1999-11-01), None
patent: WO 9957119 (1999-11-01), None
patent: WO 9957120 (1999-11-01), None
N. W. Tietz, ed., “Textbook of Clinical Chemistry” (W.B. Saunders Co., Philadelphia, 1986), pp. 882-886.
G.A. Lyles & B.A. Callingham, “The Effects of Thyroid Hormones on Monoamine Oxidase in the Rat Heart,”J. Pharm. Pharmacol. 26: 921-930 (1974).
S.K. Gupta & R.K. Mishra, “Desensitization of D1Dopamine Receptors Down-Regulates the Gsα Subunit of G Protein in SK-N-MC Neuroblastoma Cells,”J. Mol. Neurosci. 4: 117-123 (1993).
S.K. Gupta & R.K. Mishra, “Up-Regulation of D1Dopamine Receptors in SK-N-MC Cells After Chronic Treatment with SCH 23390,”Neurosci. Res. Commun. 15: 157-166 (1994).
P.W. Baures et al., “Design, Synthesis, X-Ray Analysis, and Dopamine Receptor-Modulating Activity of Mimics of the ‘C5’ Hydrogen-Bonded Conformation in the Peptidomimetic 2-Oxo-3-(R)-[(2(S)-Pyrrolidinylcarbonyl)amino]-1-Pyrrolidineacetamide,”J. Med. Chem. 37: 3677-3683 (1994).
J.E. Savelli et al., “Modulation of N-Methyl-D-Aspartate (NMDA) Antagonist-Induced Darting Behaviour by the Peptidomimetic PAMTA,”Brain Res. 682:41-49 (1995).
K.A. Jacobson, “Chemical Approaches to the Definition of Adenosine Receptors”in Adenosine Receptors(D.M.F. Cooper & C. Londos, eds.,Receptor Biochemistry and Methodology, J.C. Venter, L.C. Harrison, eds., Alan R. Liss: New York, 1988), pp. 11:1-26.
S.H. Appel & J.L. McManaman, “Is a Breakdown of the Blood-Brain Barrier Cause or Effect?,”Neurobiol. Aging7:512-514 (1986).
S.M. MacDonald et al., “Immunological Parameters in the Aged and in Alzheimer's Disease,”Clin. Exp. Immunol. 49:123-128 (1982).
A.E. Miller et al., “Immunological Studies in Senile Dementia of the Alzheimer Type: Evidence for Enhanced Suppressor Cell Activity,”Ann. Neurol. 10:506-510 (1981).
K. Stefansson, “Neuroimmunology of Aging”in Clinical Neurology of Aging(M.L. Albert, ed., Oxford University Press, Oxford, (1984)), ch. 4, pp. 76-94.
L.R. Weitkamp et al., “Alzheimer Disease: Evidence for Susceptibility Loci on Chromosomes 6 and 14,”Am. J. Hum. Genet. 35:443-53 (1983).
A. Yamakazi et al., Synthesis of Guanosine and Its Derivatives from 5-Amino-1-β-D-Ribofuranosyl-4-Imidazolecarboxamide I. Ring Closure with Benzoyl Isothiocyanate,J. Org. Chem. 32:1825-1828 (1967).
B. Alhede et al., “A Simple and Efficient Synthesis of 9-Substituted Guanines. Cyclodesulfurization of 1-Substituted 5[(Thiocarbamoyl)amino]imidazole-4-carboxamides under Aqueous Basic Conditions,”J. Org. Chem. 56:2139-2143 (1991).
R.E. Callard & A.J.H. Gearing, “The Cytokine Facts Book” (Academic Press, London, 1994), pp. 99-100, 104-105, 191-200, 235-237.
P.J. Middlemiss et al., “AIT-082, a Unique Purine Derivative, Enhances Nerve Growth Factor Mediated Neurite Outgrowth from PC12 Cells,”Neurosci. Lett.199: 131-134 (1995).
K.L. Audus et al., “Brain Uptake of Drugs: the Influence of Chemical and Biological Factors,”Adv. Drug Res.23: 1-64 (1992).
W.A. Banks & A.J. Kastin, “Measurement of Transport of Cytokines Across the Blood-Brain Barrier,”Meth. Neurosci.16: 67-77 (1993).
A.L. Betz, “Identification of Hypoxanthine Transport and Xanthine Oxidase Activity in Brain Capillaries,”J. Neurochem.44: 574-579 (1985).
F.G. Blasberg et al., “Transport of α-Aminoisobutyric Acid Across Brain Capillary and Cellular Membranes,”J. Cereb. Blood Flow Metab.3: 8-32 (1983).
E.M. Cornford & W.H. Olendorf, “Independent Blood-Brain Barrier Transport Systems for Nucleic Acid Precursors,”Biochim. Biophys. Acta394: 211-219 (1975).
A.J. Glasky et al., “Effect of AIT-082, a Purine Analog, on Working Memory in Normal and Aged Mice,”Pharmacol. Biochem. Behav.47: 325-329 (1994).
A.J. Glasky et al., “Neurotrophins, Growth Factors and Mimetic Agents as Neuroprotectors in the Treatment of Alzheimer's Disease”in Alzheimer Disease: From Molecular Biology to Therapy(R. Becker & E. Giacobini, eds., Birkhäuser, Boston, 1996), pp. 119-124.
E.G. Gutierrez et al., “Murine Tumor Necrosis Factor Alpha Is Transported from Blood to Brain in the Mouse,”J. Neuroimmunol.47: 169-176 (1993).
M. Hosokawa & M. Ueno, “Aging of Blood-Brain Barrier and Neuronal Cells of Eye and Ear in SAM Mice,”Neurobiol. Aging20: 117-123 (1999).
M.D. Johnson & B.D. Anderson, “Localization of Purine Metabolizing Enzymes in Bovine Brain Microvessel Endothelial Cells: An Enzymatic Blood-Brain Barrier for Dideoxynucleosides?,”Pharm. Res.13: 1881-1886 (1996).
A.D. Mooradian, “Effect of Aging on the Blood-Brain Barrier,”Neurobiol. Aging9: 31-39 (1988).
W. Pan et al., “Permeability of the Blood-Brain Barrier to Neurotrophins,”Brain Res.788: 87-94 (1998).
W.M. Pardridge, “CNS Drug Design Based on Principles of Blood-Brain Barrier Transport,”J. Neurochem.70: 1781-1792 (1998).
J.F. Poduslo et al., “Macromolecular Permeability Across the Blood-Nerve and Blood-Brain Barriers

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