Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Reexamination Certificate
2011-08-23
2011-08-23
Balasubramanian, Venkataraman (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
C544S323000, C544S324000, C544S331000, C544S332000, C514S272000, C514S269000, C514S252020, C514S252100
Reexamination Certificate
active
08003789
ABSTRACT:
This invention concerns the use of compounds of formulathe N-oxides, pharmaceutically acceptable addition salts, quaternary amines, stereochemically isomeric forms thereof, wherein -a1=a2-a3=a4- forms phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl with the attached vinyl group; n is 0 to 5; R1is hydrogen, aryl, formyl, C1-6alkylcarbonyl, C1-6alkyl, C1-6alkyloxycarbonyl, substituted C1-6alkyl, substituted C1-6alkyloxyC1-6alkylcarbonyl; R2is hydroxy, halo, optionally substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl, C3-7cycloalkyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, —NHC(═O)R6, —C(═NH)R6, 5-membered heterocyclic ring; L is optionally substituted C1-10alkyl, C2-10alkenyl, C2-10alkynyl or C3-7cycloalkyl; or —X—R3; Q is hydrogen, C1-6alkyl, halo, polyhalo-C1-6alkyl, optionally substituted amino group; Y represents hydroxy, halo, C3-7cycloalkyl, optionally substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono-or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, 13 NHC(═O)R6,—C(═NH)R6, aryl; for the treatment of subjects suffering from HIV infection.
REFERENCES:
patent: 3459731 (1969-08-01), Gramera et al.
patent: 4659363 (1987-04-01), Hubele et al.
patent: 4694009 (1987-09-01), Hubele et al.
patent: 5017466 (1991-05-01), Kobayashi et al.
patent: 5691364 (1997-11-01), Buckman et al.
patent: 6048866 (2000-04-01), Hutchings et al.
patent: 6093716 (2000-07-01), Davis et al.
patent: 6197779 (2001-03-01), Andries et al.
patent: 6200977 (2001-03-01), Cushing et al.
patent: 6528513 (2003-03-01), Cushing et al.
patent: 6835726 (2004-12-01), Cushing et al.
patent: 6878717 (2005-04-01), De Corte et al.
patent: 7037917 (2006-05-01), De Corte et al.
patent: 0 135 472 (1984-07-01), None
patent: 0135472 (1985-03-01), None
patent: 0 588 762 (1993-08-01), None
patent: 0371139 (1994-10-01), None
patent: 0834507 (1998-04-01), None
patent: 0945442 (1999-09-01), None
patent: 0945443 (1999-09-01), None
patent: WO 95/10506 (1995-04-01), None
patent: WO 97/18839 (1997-05-01), None
patent: WO 97/19065 (1997-05-01), None
patent: WO 98/41512 (1998-09-01), None
Arnold, et al., Inhibitor conformational flexibility and positional variation are important for activity against drug-resistant virus: crystal structures of highly potent non-nucleoside inhibitors of HIV-1 reverse transcriptase, 21stEuropean Crystallographic Meeting, Durban, South Africa, Aug. 24-29, 2003.
Arnold, Conformational Flexibility of DAPYs: activity against resistant HIV, Aug. 2003.
Blagović, et al.,Validation of a Model for the Complex of HIV-1 Reverse Transcriptase with Nonnuceloside Inhibitor TMC125, J. Am. Chem. Soc. 2003, vol. 125, pp. 6016-6017.
Clark, Inhibitor conformational flexibility and positional variation are important for activity against drug-resistant virus: crystal structures of highly potent non-nucleoside inhibitors of HIV-1 reverse transcriptase, 21stEuropean Crystallographic Meeting, Durban, S. Africa, Aug. 24-29, 2003.
Das, et al., Could multiple modes of binding of a potent NNRTI TMC125-R165335 explain its potency against common drug-resistant mutants?, CROI, Boston, Feb. 2003.
M-P. de Bethune, TMC 125 resistance profiles, Resistance, Mexico, Jun. 2003.
Furukawa, et al., Syntheses of Compounds related to Guanidine and their Inhibitory Action on Growth of HeLa Cells, Chem. Pharm. Bull. 9 (11), 914-921 (1951).
Gazzard, et al., TMC125, A Next-Generation NNRTI, Demonstrates High Potency After 7 Days Therapy in Treatment-Experienced HIV-1 Infected Individuals with Phenotypic NNTRI , CROI, Seattle, Feb. 2002.
Gazzard, et al.,An open-label assessment of TMC 125—a new, next-generation NNRTI, for 7 days in HIV-1 infected individuals with NNRTI resistance, AIDS 2003, vol. 17, pp. 49-54.
Gazzard, et al., TMC125, a Next Generation NNTRI, Demonstrates High Potency After 7 Days Therapy in Treatment-Experienced HIV-1 Infected Individuals with Phenotypic NNRTI-Resistance, XIV International Aids Conference, Jul. 7-11, 2003, Barcelona, Spain.
Gazzard, TMC 125 C207 study treatment-experienced, CROI Seattle, Feb. 2002.
Gazzard, 7 day treatment-experienced, WAC Barcelona, Jul. 2002.
Gruzdev, et al.,A Randomized, double-blind, placebo-controlled trial of TMC125 as 7-day monotherapy in antiretroviral naïve HIV-1 infected subjects, AIDS 2003, vol. 17, pp. 2487-2494.
Gulick, New Antiretroviral Drugs, Clinical Microbiology and Infectious Diseases, CMI, 9, (3) pp. 186-193 (Mar. 2003).
Lange, TMC 125 decay rate vs ERA, CROI Seattle, Feb. 2002.
Lewi, Potency & multiple binding modes of TMC 125, CROI Boston, Feb. 2003.
Ludovici, et al.,Evolution of Anti-HIV Drug Candidates. Part 3: Diarylpyrimidine(DAPY)Analogues, Bioorganic & Medical Chemistry Letters 11, 2001, pp. 2235-2239.
Sankatsing, et al., TMC 125 Monotherapy for One Week Results in a Similar Initial Rate of Decline of HIV-1 RNA as Therapy With a 5-Drug Regimen, CROI, Seattle, Feb. 2002.
Sankatsing, et al.,TMC125 exerts similar initial antiviral potency as a five-drug, triple class antiretroviral regimen, Aids 2003, vol. 17, pp. 2623-2627.
TMC 125 for 7 days in HIV-1+ individuals with NNRTI resistance (TMC 125-C207), AIDS, 17 (18): F49-54, Dec. 5, 2003.
TMC 125 as 7d monotherapy in ARV-naïve subjects (TMC 125-C208), AIDS, 17(17): 2487-2494, Nov. 21, 2003.
TMC 125 similar potency to 5-drug, 3-class regimen, AIDS, 17(18): 2623-2627 Dec. 5, 2003.
Udier-Blagović, et al., Validation of a Model for the Complex of HIV-1 Reverse Transcriptase with Nonnucleoside Inhibitor TMC125,J. Am Chem. Soc. 2003, vol. 125, pp. 6016-6017.
Vingerhoets, et al., Antiviral activity of TMC125, a potent next-generation NNRTI, against > 5000 recombinant clinical isolates exhibiting a wide range of (NNRTI) resistance, XIIth International HIV Drug Resistance Workshop, Jun. 10-14, 2003, Mexico.
Vingerhoets, et al., Antiviral activity of TMC Against a Panel of Site-Directed Mutants Encompassing Mutations Observed In Vitro and In Vivo, Poster No. 621, Presented at the XIth Conference on Retrovirus and Opportunistic Infections, Feb. 8-11, 2004, San Francisco, CA USA.
Vingerhoets, Antiviral activity TMC 125 SDM CROI, San Francisco, Feb. 2004.
Vingerhoets, et al., Characterization of Resistance Before and After Short-Term Therapy with TMC125 in Patients with Documented NNRTI Resistance, XIIth International HIV Drug Resistance Workshop, Jun. 10-14, 2003, Mexico.
Vingerhoets, Resistance before/after therapy—TMC 125C207, XII Resistance Mexico, Jun. 2003.
Vingerhoets, Resistance profile clinical isolates TMC 125, XII Resistance, Jun. 2003, Mexico.
Vingerhoets, TMC-125-C207 resistance analysis, Resistance, Jun. 2003, Mexico.
Udier-Blagović, et al., Validation of a Model for the Complex of HIV-1 Reverse Transcriptase with Nonnucleoside Inhibitor TMC125,J. Am< Chem. Soc. 2003, vol. 125, pp. 6016-6017.
Rudi Pauwels et al., “Potent and highly selective human immunodeficiency virus type 1 (HIV-1) inhibition by a series of α-anilinophenylacetamide derivatives targeted at HIV-1 reverse transcriptase”, Proc. Natl. Acad. Sci. USA, (Mar. 1993), pp. 1711-1715, vol. 90.
International Search Report mailed Feb. 2, 2000 for related International Application No. PCT/EP1999/07417.
Koyanagi, Y., et al. “Selective Cytotoxicity of AIDS Virus Infection Towards HTLV-I-Transformed Cell Lines”, Int. J. Cancer, vol. 36 (1985) pp. 445-451.
McOmie, J., “Protective Groups in Organic Chemistry”, (1973) Title Page and Table of Contents.
T.W. Greene & P.G.M. Wutz (eds.), Protective Groups in Organic Synthes
Andries Koenraad Jozef Lodewijk Marcel
Arts, legal representative Frank Xavier Jozef Herwig
De Corte Bart
de Jonge Marc René
Heeres Jan
Balasubramanian Venkataraman
Janssen Pharmaceutica N.V.
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