Method and compositions for the synthesis of BCH-189 and related

Details Method and compositions for the synthesis of BCH-189 and related Method and compositions for the synthesis of BCH-189 and related

1993-02-10

1996-07-23

Tsang, Cecilia

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

Organic compounds

Nitrogen attached directly or indirectly to the purine ring...

544229, 544313, 544314, 544318, C07D41104, C07F 502, A61K 31505

Patent

active

055391168

ABSTRACT:
The present invention relates to a method of preparing BCH-189 and various analogs of BCH-189 from inexpensive precursors with the option of introducing functionality as needed. This synthetic route allows the stereoselective preparation of the biologically active isomer of these compounds, .beta.-BCH-189 and related compounds. Furthermore, the steochemistry at the nucleoside 4' position can be controlled to produce enantiomerically-enriched .beta.-BCH-189 and its analogs.

REFERENCES:
patent: 4000137 (1976-12-01), Dvonoch et al.
patent: 4336381 (1982-06-01), Nagata et al.
patent: 4861759 (1989-08-01), Mitsuya et al.
patent: 4879277 (1989-11-01), Mitsuya et al.
patent: 4916122 (1990-04-01), Chu et al.
patent: 4963533 (1990-10-01), de Clerq et al.
patent: 5011774 (1991-04-01), Farina et al.
patent: 5041449 (1991-08-01), Bellean et al.
patent: 5047407 (1991-09-01), Bellean et al.
patent: 5059690 (1991-10-01), Zahler et al.
Journal of Aquired Immune Deficiency Syndromes vol. 6, No. 1, 1993.
Dean L. Winslow et al, AIDS, 1994, vol. 8, No. 6 pp.753-755.
Balzarini, J., et al., "Potent and Selective Anti-HTI V-III/LAV Activity of 2',3'-Dideoxycytidinene, the 2',3'-Unsaturated Derivative of 2',3'-Dideoxycytidine," Biochemical and Biophysical Research Communications, vol. 140, No. 2, pp. 735-742 (1986).
Carter, et al., "Activities of (-)-Carbovir and 3'-Azido-3'-Deoxythymidine Against Human Immunodeficiency Virus In Vitro," Antimicrobial Agents and Chemotherapy, vol. 34, No. 6, pp. 1297-1300 (1990).
Chang, Chien-Neng, et al., "Deoxycytidine Deaminase-resistant Stereoisomer Is the Active Form of (.+-.)-2',3'-Dideoxy-3'-thiacytidine in the Inhibition of Hepatitus B Virus Replication," The Journal of Biological Chemistry, vol. 357, No. 20, pp. 13938-13942 (1992).
Chu, et al., "Structure-Activity Relationships of Pyrimidine Nucleosides as Antiviral Agents for Human Immunodeficiency Virus Type 1 in Peripheral Blood Mononuclear Cells," J. Med. Chem.vol. 32, p. 612 (1989).
Chu, et al., "Comparative Activity of 2',3'-Saturated and Unsaturated Pyrimidine and Purine Nucleosides Against Human Immunodeficiency Virus Type 1 in Peripheral Blood Mononuclear Cells," Biochem. Pharm., vol. 37, No. 19, pp. 3543-3548 (1988).
Chu, C. K., et al., "An Efficient Total Synthesis of 3'-Azido-3'-Deoxythiymidine (AZT) and 3'-Azido-2',3'-Dideoxyuridine (AZDDU, CS-87) from D-Mannitol," Tetrahedron Lett. 1988, 5349.
Cratton, E., et al., "Catabolism of 3'-Azido-3'-Deoxythymidine in Hepatocytes and Liver Microsomes, with Evidence of Formation of 3'-Amino-3'-Deoxythymidine, a Highly Toxic Catabolite for Human Boane Marrow Cells," Molecular Pharmacology, vol. 39, pp. 258-266 (1991).
Cretton, E., et al., "Pharmokinetics of 3'-Azido-3'-Dexoythymidine and its Catabolites and Interactions with Probenecid in Rhesus Monkeys," Antimicrobial Agents and Chemotherapy, pp. 801-807 (1991).
Furman, et al., "The Anti-Hepatits B Virus Activities, Cytotoxicities, and Anabolic Profiles of the (-) and (+) Enantiomers of cis-5-Fluoro-1-[2-(Hydromethyl)-1,3-Oxthiolan-5-yl]Cytosine," Antimicrobial Agents and Chemotherapy, vol. 36, No. 12, pp. 2686-2692 (1992).
Jeong, L., et al., "Asymmetric Synthesis and Biological Evaluation of .beta.-L-(2R,5S)--and .alpha.-L-(2R-5R)-1,3-Oxathiolane-Pyrimidine and -Purine Nucleosides and Potential Anti-HIV Agents," J. Med. Chem., vol. 36 (1993).
Lin, et al., "Potent and Selective In Vitro Activity of 3'-Deoxythmindin-2-Ene-(3'-Deoxy-2',3'-Didehydrothymidine) Against Human Immunodeficiency Virus," Biochem. Pharm., vol. 36, No. 17, p. 2716 (1987).
Mitsuya, H., et al., "Rapid in Vitro Systems for Assessing Activity of Agents Against HTLV-III/LAV," AIDS: Modern Concepts and Therapeutic Challenges, S. Broder, Ed. (Marcel-Dekker, New York), (1987), p. 303.
Mitsuya, J., et al., "3'-Azido-3'-Deoxythymidine (BW A 509U): An Antiviral Agent that Inhibits the Infectivity and Cytopathic Effect of Human T-Lymphotropic Virus Type III/Lymphadenopathy-Associated Virus In Vitro", Proc. Natl. Acad. Sci., USA, vol. 82, pp. 7097-7100 (1985).
Mitsuya, H., et al., "Molecular Targets for AIDS Therapy," Science, vol. 249, pp. 1533-1544 (1990).
Norbeck, D., et al., "A New 2',3'-Dideoxynucleoside Prototype with In Vitro Activity Against HIV," Tetrahedron Lett. 1989, 6263.
Okabe, M., et al., "Synthesis of the Dideoxynucleosides ddC and CNT from Glutamic Acid, Ribonolactone, and Pyrimidine Bases," J. Org. Chem. 1989.
Richman, D. D., et al., "The Toxicity of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDS-Related Complex," N. Eng. J. Med. 1987, 317:192.
Satsumabayashi, S. et al., "The Synthesis of 1,3-Oxathiolan-5-one Derivatives," Bull. Chem. Soc. Japan, 1972, 45,913.
Schinazi, R. F., et al., "Activities of the Four Optical Isomers of 2',3'-Dideoxy-3'-Thiacytidine (BCH-189) against Human Immunodeficiency Virus Type 1 in Human Lymphocytes," Antimicrobial Agents and Chemotherapy 36(3) 672-676 (1992).
Schinazi, R. F., et al., "Insights into HIV Chemotherapy," AIDS Research and Human Retroviruses 8(6) (1992) 963-990.
Schinazi, R. F., et al., "Pharmacokinetics and Metabolism of Racemic 2',3'-Dideocy-5-Fluoro-3'-Thiacytidine in Rhesus Monkeys," Antimicrobial Agents and Chemotherapy 36(11) 2432-2438 (1992).
Schinazi, R. F., et al., "Selective Inhibition of Human Immunodeficiency Viruses by Racemates and Enantiomers of cis-5-Fluoro-1-[2-(Hydroxymethyl)-1,3-Oxathiolan-5-yl]Cytosine," Antimicrobial Agents and Chemotherapy 36(11) 2423-2431 (1992).
Schinazi, R. F., et al., "Substrate Specificity of Escherichia Coli Thymidine Phosphorylase for Pyrimidine Nucleoside with and Anti-Human Immunodeficiency Virus Activity," Biochemical Pharmacology 44(2) (1992) 199-204.
Vorbr uggen et al, "Nucleoside Synthesis with Trimethylsilyl Triflate and Perchlorate as Catalysts," Chem. Ber. 1981, 114:1234-1255.
Belleau, B., et al., "Design and Acitvity of a Novel Class of Nucleoside Analogs Effective Against HIV-1," 5th International Conference on AIDS, Montreal, Quebec, Canada, Jun. 4-9, 1989.
Storer, Richard, et al., "The Resolution and Absolute Stereochemistry of the Enantiomers of cis-1-[2-(Hydroxymethyl)-1,3-Oxathiolan-5-yl)Cytosine(BCH189): Equipotent Anti-HIV Agents," Nucleosides & Nucleotides, 12(2), 225-236 (1993).
Wilson, L. J., et al., "A General Method for Controlling Glycosylation Stereochemistry in the Synthesis of 2'-Deoxyribose Nucleosides," Tetrahedron Lett. 1990, 1815.
Zhu, Zhou, et al., "Cellular Metabolism of 3'-Azido-2',3'-Dideoxyuridine with Formation of 5'-O-Diphophoshexase Derivatives by Previously Unrecognized Metabolic Pathways of 2'-Deoxyuridine Analogs," Molecular Pharmacology, vol. 38, pp. 929-938 (1990).
Hoong et al, Journal of Organic Chem. 1992, vol. 57, pp. 5563-5565.
U.S. application Ser. No. 07/686,617 filed Apr. 17, 1991 Cheng.
U.S. application Ser. No. 07/718,806 filed Jun. 21, 1991 Cheng.
U.S. application Ser. No. 07/785,545 filed Oct. 31, 1991 Cheng.

Affiliated with

Also associated with

Rating

Method and compositions for the synthesis of BCH-189 and related does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Method and compositions for the synthesis of BCH-189 and related, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method and compositions for the synthesis of BCH-189 and related will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-714209