Carbamoyl-and thiocarbamoyl-phosphonates and pharmaceutical...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...

Reexamination Certificate

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C562S015000

Reexamination Certificate

active

07345033

ABSTRACT:
The present invention provides a compound of the following formula I:in-line-formulae description="In-line Formulae" end="lead"?R3—NH—C(═X)—P(═O)OR1OR2in-line-formulae description="In-line Formulae" end="tail"?including pharmaceutically acceptable salts, solvates, hydrates and polymorphs of the compounds of formula I, as well as geometrical isomers and optically active forms of the compounds of formula I and pharmaceutically acceptable salts, solvates, hydrates and polymorphs of said isomers and forms,whereinR1and R2may be the same or different and are each selected from hydrogen, acyloxyalkyl and aryl or R1and R2may form together with the oxygen and phosphorus atoms a dioxaphosphacycloalkane ring;X is O or S; andR3is selected, when X is O, from bicycloalkyl, cycloalkylalkyl and substituted cycloalkyl by at least one of alkyl, amino, amidino and guanidino; and R3is selected, when X is S, from bicycloalkyl, cycloalkylalkyl and cycloalkyl optionally substituted by at least one of alkyl, amino, amidino and guanidino; with the proviso that:when X is O, R3is not cyclohexylmethyl, andwhen X is S, R3is not cyclohexyl.The invention further provides pharmaceutical compositions comprising the above compounds and their use in medicine.

REFERENCES:
patent: WO 01/26661 (2001-04-01), None
patent: WO 01/26661 (2001-04-01), None
Whittaker et al., “Design and Therapeutic Application of Matrix Metalloproteinase Inhibitors”,Chem. Rev.vol. 99, pp. 2735-2776, 1999.
Chen et al., “Long-Chain Functional Bisphosphonates: Synthesis, Anticalcification, and Antiresorption Activity”,Heteroatom Chemistry, vol. 11, No. 7, pp. 470-479, 2000.
Salomon et al., “Efficient and Selective Dealkylation of Phosphonate Dilsopropyl Esters Using Me3SiBr”,Tetrahedron Letters, vol. 36, No. 37, pp. 6759-6760, 1995.
Cava et al., “Thionation Reactions of Lawesson's Reagents”,Tetrahedron, vol. 41, No. 22, pp. 5061-5087, 1985.
Ferenc Fulop, “The Chemistry of 2-Aminocycloalkanecarboxylic Acids”,Chem. Rev.vol. 101, pp. 2181-2204, 2001.
Makomo et al., “Catalyzed Amination of Dithioacid Sodium Salts: A One Pot Synthesis of α-Phosphonothioamides”,Phosphorous, Sulfur, and Silicon, vol. 80, pp. 31-36, 1993.

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