Benzylated PDE4 inhibitors

Details Benzylated PDE4 inhibitors Benzylated PDE4 inhibitors

2007-03-08

2008-12-02

Shiao, Rei-tsang (Department: 1626)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C548S543000

Reexamination Certificate

active

07459479

ABSTRACT:
The present invention is directed to a method for reducing the emetogenic effects of PDE inhibitors, and more particularly is directed to compounds having PDE4 inhibition activity with little or no emetogenic side-effects, and chemical methods including benzylation for preparing such compounds. A benzyl group may be attached to either a carbon or nitrogen atom of a PDE4 inhibitor. Suitable benzylation chemistry is to extract a hydrogen from a PDE4 inhibitor, preferably with a base, and then react the resulting nucleophilic PDE4 inhibitor with a benzylating agent, e.g., benzyl bromide or a derivative thereof.

REFERENCES:
patent: 3636039 (1972-01-01), Gruenman et al.
patent: 4308278 (1981-12-01), Schneider et al.
patent: 4950674 (1990-08-01), Yanni et al.
patent: 5066663 (1991-11-01), Hobbs
patent: 5124455 (1992-06-01), Lombardo
patent: 5223504 (1993-06-01), Noverola et al.
patent: 5444083 (1995-08-01), Yamanaka et al.
patent: 5552438 (1996-09-01), Christensen, IV
patent: 5563143 (1996-10-01), Cohan et al.
patent: 5602157 (1997-02-01), Christensen, IV
patent: 5602173 (1997-02-01), Christensen, IV
patent: 5728844 (1998-03-01), Muller et al.
patent: 5734051 (1998-03-01), Spicer et al.
patent: 5814651 (1998-09-01), Duplantier et al.
patent: 5916910 (1999-06-01), Lai
patent: 5965730 (1999-10-01), Ukita et al.
patent: 5968945 (1999-10-01), Muller et al.
patent: 6004974 (1999-12-01), Duplantier et al.
patent: 6028086 (2000-02-01), Duplantier
patent: 6555572 (2003-04-01), Lauener et al.
patent: 381 235 (1990-08-01), None
patent: WO 92/12961 (1992-08-01), None
patent: WO 92/19594 (1992-11-01), None
patent: WO 93/07141 (1993-04-01), None
patent: WO 94/12461 (1994-06-01), None
patent: WO 95/00139 (1995-01-01), None
patent: WO 98/34584 (1998-08-01), None
patent: WO 99/18793 (1999-04-01), None
patent: WO 99/34797 (1999-07-01), None
patent: WO 99/34798 (1999-07-01), None
Piaz, “Novel Heterocyclic-Fused Pyridazinones as Potent and Selective Phosphodiesterase IV Inhibitors”, Journal of Medicinal Chemistry 40(10): 1417-1421, 1997.
Sugden, “Some pyrrolidine analogues of diphenatil and related substances”, Pharm. Acta Helv. 49(7/8): 268-269, 1974.
Ashton et al., “Selective Type IV Phosphodiesterase Inhibitors as Antiasthmatic Agents. The Syntheses and Biological Activities of 3-(Cyclopentyloxy)-4-methoxybenzamides and Analogues,”J. Med. Chem. 37:1696-1703, 1994.
Bacher et al., “N-Arylrolipram Derivatives as Potent and Selective PDE4 Inhibitors,”Bioorganic&Medicinal Chemistry Letters 8:3229-3234, 1998.
Beasley et al., “Synthesis and Evaluation of a Novel Series of Phosphodiesterase IV Inhibitors. A Potential Treatment for Asthma,”Bioorganic&Medicinal Chemistry Letters 8:2629-2634, 1998.
Burnouf et al., “Phosphodiesterases 4 Inhibitors,” in James A. Bristol, (ed.),Annual Reports In Medicinal Chemistry vol. 33, Academic Press, California, 1998, Chap. 10, pp. 91-109.
Christensen et al., “Molecular Aspects of Inhibitor Interaction With PDE4,” in Schudt et al., (eds.),Phosphodiesterase Inhibitors, Academic Press, 1996, Chap. 13, 185-207.
Christensen et al., “1,4-Cyclohexanecarboxylates: Potent and Selective Inhibitors of Phosophodiesterase 4 for the Treatment of Asthma,”J. Med. Chem. 41:821-835, 1998.
Bärfacker et al., “Rhodium(I)-catalysed Hydrocarbonylation and Silylcarbonylation Reaction of Alkynes in the Presence of Primary Amines Leading to 2-Pyrrolidinones and 4-Silyated 1-Aza-1,3-butadienes,”Tetrahedron 54(18):4493-4506, Apr. 30, 1998.
Cook et al., “Process Development of the PDE IV Inhibitor 3-(Cyclopentyloxy)-N-(3,5-dichloropyrid-4-yl)-4-Methoxybenzamide,”Organic Process Research&Development 2(3):157-168, 1998.
Crespo et al., “Design, Synthesis, and Biological Activities of New Thieno[3,2-d]pyrimidines as Selective Type 4 Phosphodiesterase Inhibitors,”J. Med. Chem. 41:4021-4035, 1998.
Duplantier et al., “Biarylcarboxylic Acids and -Amides: Inhibition of Phosphodiesterase Type IV versus [3H]Rolipram Binding Activity and Their Relationship to Emetic Behavior in the Ferret,”J. Med. Chem. 39(1):120-125, 1996.
Essayan, “Cyclic Nucleotide Phosphodiesterase (PDE) Inhibitors and Immunomodulation,”Biochemical Pharmacology 57(9):965-973, May 1, 1999.
Karlsson and Aldous, “Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis,”Expert Opnion on Therapeutic Patents 7(9):989-1003, 1997.
Küsters and Spöndlin, “Influence of Temperature on the Enantioseparation of Rolipram and Structurally Related Racemates on Chiracel-OD,”Journal of Chromatography 737(2):333-337, Jun. 21, 2001.
Macdonald et al., “Hunting and Emesis and Efficacy Targets of PDE4 Inhibitors: Identification of the Photoaffinity Probe 8-(3-Azidophenyl)-6-[(4-iodo-1H-1-imidazolyl)methyl]quinoline (APIIMQ),”J. Med. Chem. 43(21):3820-3823, 2000.
Marivet et al., “Inhibition of Cyclic Adenosine-3′,5′-Monophosphate Phosphodiesterase From Vascular Smooth Muscle by Rolipram Analogues,”J. Med. Chem. 32(7):1450-1457, 1989.
Newton et al., “Therapeutic Potential and Strategies for Inhibiting Tumor Necrosis Factorα,”J. of Medicinal Chemistry 42(13):2295-2314, 1999.
Norman, “PDE4 Inhibitors 1999,”Exp. Opin. Ther. Patents 9(8):1-18, 1999.
Norman, “PDE4 Inhibitors: Patent and Literature Activity 1999-mid 2000,”Exp. Opin. Ther. Patents 10(9):1417-1429, 2000.
Piaz et al., “Phosphodiesterase 4 Inhibitors, Structurally Unrelated to Rolipram, as Promising Agents for the Treatment of Asthma and Other Pathologies,”Eur. J. Med. Chem. 35:463-480, 2000.
Robichaud et al., “Emesis Induced by Inhibitors of Type IV Cyclic Nucleotide Phosphodiesterase (PDE IV) in the Ferret,”Neuropharmacology 38:289-297, 1999.
Robichaud et al, “PDE4 Inhibitors Induce Emesis in Ferrets Via a Noradrenergic Pathway,”Neuropharmacology 40:262-269, 2001.
Rowley et al., “4-Heterocyclylpiperidines as Selective High-Affinity Ligands at the Human Dopamine D4 Receptor,”J. Med. Chem. 40:2374-2385, 1997.
Souness et al., “Potential of Phosphodiesterase Type IV Inhibitors in the Treatment of Rheumatoid Arthritis,”Idrugs 1(5):541-553, 1998.
Souness et al., “Immunosuppressive and Anti-Inflammatory Effects of Cyclic AMP Phosphodiesterase (PDE) Type 4 Inhibitors,”Immunopharmacology 47:127-162, 2000.
Spina, “The Potential of PDE4 Inhibitors in Asthma or COPD,”Current Opinion in Investigational Drugs 1(2):204-213, 2000.
Tian et al., “Dual Inhibition of Human Type 4 Phosphodiesterase Isostates by (R*,R*)-(±)-Methyl 3-Acetyl-4-[3-(cyclopentyloxy)-4-methoxyphenyl]-3-methyl-1-pyrrodlidinecarboxylate,”Biochemistry 37(19):6894-6904, 1998.
Torphy, “Phosphodiesterase Isozymes Molecular Targets for Novel Antiasthma Agents,”American Journal of Respiratory and Critical Care Medicine 157(2):351-370, Feb. 1998.
Chemabs Database, STN Accession No. 83:37487, 1974.

Affiliated with

Also associated with

Rating

Benzylated PDE4 inhibitors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Benzylated PDE4 inhibitors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Benzylated PDE4 inhibitors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-4033845