Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Reexamination Certificate
2006-03-28
2006-03-28
Richter, Johann (Department: 1621)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
C514S080000
Reexamination Certificate
active
07018988
ABSTRACT:
The present invention is related to new substituted pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of neurodegenerative disorders, diseases associated with polygultamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders renal hypoxia, hepatitis and AIDS. Said pyrrolidine derivatives display a modulatory and most notably a down-regulating-up to an inhibitory-activity with respect to the cellular death agonist Bax and/or the activation pathways leading to Bax and allows therefore to block the release of cytochrome (c). The present invention is furthermore related to novel pharmaceutically activity substituted pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of O, S, CR<6>R<7>, NOR<6>, NNR<6>R<7>; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO2—, —SO2NH—; —CH2—; B is either a group —(C═O)—NR<8>R<9> or represents a heterocyclic residue having the formula (II) wherein Q is NR<10>, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5–6 membered aryl or heteroaryl ring.
REFERENCES:
patent: 3555007 (1971-01-01), Magerlein
patent: 3674647 (1972-07-01), Visser
patent: 4278681 (1981-07-01), Haskell et al.
patent: 4734508 (1988-03-01), Thottathil
patent: 4851514 (1989-07-01), Thottathil
patent: 5514683 (1996-05-01), Kalindjian et al.
patent: 1 932 823 (1970-01-01), None
patent: 1118306 (1968-06-01), None
patent: WO 95/04718 (1995-02-01), None
patent: WO 95/52868 (1999-10-01), None
patent: WO 00/08015 (2000-02-01), None
Pedersen et al. “Studies on Organophosphorus Compounds XX. Syntheses of Thioketones”Bull. Soc. Chim. Belg.vol. 87, No. 3, 1978.
Sufrin et al. “Synthetic Approaches to Peptide Analogs Containing 4, 4-Difluoro-L-Proline and 4-Keto-L-Proline”Int. J. Pept. Protein Res.(1982), 20(5), 438-42.
Komai et al. “Structure-activity Relationships of HIV-1 PR Inhibitors Containing AHPBA-II. Modification of Pyrrolidine Ring at P11Proline”Bioorg. Med Chem.(1996), 4(8), 1365-1377.
Bray et al. “Rapid Optimization of Organic Reactions on Solid Phase using the Multipin Approach: Synthesis of 4-Aminoproline Analogues by Reductive Amination”Tetrahedron Letters(1995), 36(28), 5081-5084.
Nicolaides et al. “Modified Di- and Tripeptides of the C-Terminal Portion of Oxytocini and Vasopressin as Possible Cognition Activation Agents”Journal of Medicinal Chemistry, American Chemical Society(1986) 29(6) 959-971.
Jacobson “Apoptosis: Bcl-2-Related Proteins get Connected”Current Biology(1977) R277-R281.
Kroemer “The Proto-Oncogene Bcl-2 and its Role in Regulating Apoptosis”Nature Medicine6(1997), 3(6), 614-620.
Reed “Double Identity for Proteins of the Bcl-2 Family”Nature6(1997) 387: 773-776.
Kelekar et al. “Bcl-2-Family Proteins: The Role of the BH3 Domain in Apoptosis”Trends in Cell Biology8(1998) 8: 324-330.
Martinou et al. “Viral Proteins E1B19K and p35 Protect Sympathetic Neurons from Cell Death Induced by NGF Deprivation”The Journal of Cell Biology1(1995) 128(1 & 2) 201-208.
Deckwerth et al. “BAX is Required for Neuronal Death after Trophic Factor Deprivation and During Development”Neuron9(1996) 17: 401-411.
Antonsson et al. “Bax Oligomerization is Required for Channel-Forming Activity in Liposomes and to trigger Cytochrome c Release from Mitochondria”Biochemical Journal(2000) 345: 271-278.
Desagher et al. “Bid-inducec Conformational Change of BAX is Responsible for Mitochondrial Cytochrome c Release during Apoptosis”The Journal of Cell Biology3(1999) 144(5): 891-901.
Narukawa et al. “General and Efficient Synthesis of 2-Alkylcarbapenems: Synthesis of Dethiacarba Analogs of Clinically Useful Carbapenems via Palladium-Catalyzed Cross-Coupling Reaction”Tetrahedron1(1997) 53(2): 539-556.
Adlington et al. “A radical Route to 2(S)-4-Exomethylene Proline”Tetrahedron(1992) 48(31): 6529-6536.
Holmes et al. “The Design and Synthesis of Novel Hydroxyproline Inhibitors of HIV-1 Proteinase”Bioorganic&Medicinal Chemistry Letters(1993) 3(8): 1485-1491.
Baxter Anthony
Bombrun Agnes
Halazy Serge
Quattropani Anna
Schwarz Mattias
Applied Research Systems ARS Holding N.V.
Browdy and Neimark PLLC
Nwaonivha Chukwuma
Richter Johann
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