Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-05-09
1999-11-09
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5142278, 5142322, 5142358, 514249, 514255, 544 60, 544120, 544121, 544122, 544123, 544295, 544296, 544315, 544316, 544317, 544318, A61K 31505, A61K 31535, C07D41300, C07D23902
Patent
active
059815370
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of Invention
The pyrimidine-thioalkyl and alkylether derivatives of Formula IA are useful in the treatment of individuals who are HIV positive, whether or not they show AIDS symptoms at the present time. The pyrimidine-thioalkyl and alkylether derivatives of Formula IB are useful in the preparation of the pyrimidine-thioalkyl and alkylether derivatives of Formula IA.
2. Description of the Related Art
U.S. Pat. No. 5,025,016 (and EP 124 630) pyrimidine-thioalkyl pyridine derivatives corresponding to the general formula ##STR2## in which R.sub.1 to R.sub.4, independently of one another, represent hydrogen, lower alkyl, halogen, amino or hydroxy groups, R.sub.5 represents a free electron pair or a lower alkyl group, a halogen atom, m has the value 0 or 1, the pyrimdine-thioalkyl group being bonded in the 2-, 3- or 4- position of the pyridine ring, and to therapeutically compatible acid addition salts thereof. The compounds allegedly exhibit surprisingly improved bronchosecretolytic and myucolytic activity as well as having been found to show antiphlogistic activity.
J. Med Chem. 1987, 30, 547-551 describes various 2-[(pyridinylmethyl)thio]-pyrimidine derivatives and the influence thereof on bronchosecretolytic properties in the phenol red screening model of the mouse in comparison to the known drug ambroxol.
EP 477 778 (Derwent 92-106190/14) describes various benzene, pyridine and pyrimidine derivatives as ACAT enzyme inhibitors, for treating arteriosclerosis, and cerebrovascular disease.
J. Org. Chem, 1954, 19, 1793-1801 describes pyrimidine derivatives, including 2-benzylmercapto-4-amino-6-chloropyrimidine, 6-dimethylaminopurine.
British Patent 744,867 (CA 51:2063i) describes various 2-R'-S-6-RR'N-substituted 4-aminopyrimidines.
An estimated one to one and one-half million people in the United States are infected with a human retrovirus, the human immunodeficiency virus type I (HIV-1) which is the etiological agent of acquired immunodeficiency syndrome, AIDS, see Science, 661-662 (1986). Of those infected, an estimated two hundred and fifty thousand people will develop AIDS in the next five years, see Science, 1352-1357 (1985). On Mar. 20, 1987, the FDA approved the use of the compound, AZT (zidovudine), to treat AIDS patients with a recent initial episode of pneumocystis carinii pneumonia, AIDS patients with conditions other than pneumocystis carinii pneumonia or patients infected with the virus with an absolute CD4 lymphocyte count of less than 200/mm.sup.3 in the peripheral blood. AZT is a known inhibitor of viral reverse transcriptase, an enzyme necessary for human immunodeficiency virus replication.
U.S. Patent 4,724,232 claims a method of treating humans having acquired immunodeficiency syndrome utilizing 3'-azido-3'-deoxy-thymidine (azidothymidine, AZT).
It is known in the art that certain antibiotics and polyanionic dyes inhibit retrovirus reverse transcriptase.
Many publications have reported the ability of various sulfated compounds to inhibit virus replication, including HIV.
Nature 343, 470 (1990) and Science 250, 1411 (1990) disclose potent benzodiazepin type reverse transcriptase inhibitors. The compounds of the present invention are not benzodiazepin type compounds.
J. Org. Chem. 1962, 27, 181-185 describes various 2-benzylthio pyrimidine derivatives, including 4chloro-5-methyl-2-[(phenylmethyl)thio]-pyrimidine, 4-chloro-5-methyl-2-[[(2,4-dichloro-phenyl)methyl]thio]-pyrimidine, 4-chloro-5-methyl-2-[[(2-chloro-phenyl)methyl]thio]-pyrimidine, and 4-chloro-5-methyl-2-[[(4-chloro-phenyl)methyl]thio]-pyrimidine and their activity as antitumor compounds in screens against SA-180, CA 755, and L-1210 tumor systems.
J. Med. Chem. 1977, 20, 88-92 describes 2-alkoxy and 2-alkylthio-4amino pyrimdines, including 2-[(phenylmethyl)thio]4-pyrimidinamine, 2-[[(4-chlorophenyl)methyl]thio]-4-pyrimidinamine, 2-[(3-pyridinylmethyl)thio]4pyrimidinamine, and 2-(phenylmethoxy)-4-pyrimidinamine, and their activity as inhibitors of deoxycytidine kinase.
Collect. Czech. Chem. Comm
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Althaus Irene W.
Cleek Gary J.
Morris Joel
Murphy Michael J.
Nugent Richard A.
Coleman Brenda
Jameson William G.
Pharmacia & Upjohn Company
Raymond Richard L.
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