Bristol-Myers Squibb Compnay

Institute of Organic Chemistry and Biochemistry

Rega Stichting, V.z.w.

Peter F Misco

Choung U Kim

John C Martin

John A Wichtowski

Bing Uh Luh

Joanne J Bronson

Stanley V D'Andrea

Bing Y Luh

Yasutsugu Ueda

Muzammil M Mansuri

John D Matiskella

Shelley E Hoeft

Thomas W Hudyma

Dane M Springer

Raymond F Miller

Provided are compounds of the following formulae:

Nucleoside analogs

Novel cephem derivatives represented by the general formula ##STR1## wherein Ar is an optionally substituted lipophilic phenyl, naphthyl, benzthiazolyl or pyridyl group; R.sup.1 represents a group of the formula ##STR2## in which R.sup.8 and R.sup.9 are each independently hydrogen, C.sub.1 -C.sub.6 alkyl or (C.sub.1 -C.sub.6)alkoxycarbonyl, said C.sub.1 -C.sub.6 alkyl group being optionally substituted by 1-5 hydroxy or C.sub.1 -C.sub.6 alkoxy groups; m is either 0 or 1; A is a C.sub.2 -C.sub.10 alkyl group optionally substituted by 1-5 hydroxy groups; and R.sup.2 and R.sup.3 are each independently hydrogen or C.sub.1 -C.sub.6 alkyl. The derivatives are gram-positive antibacterial agents especially useful in the treatment of diseases caused by methicillin-resistant Staphylococcus aureus.

Cephalosporin derivatives

Provided are compounds of the following formulae: A phosphonomethoxymethyoxymethyl purine/pyrimidine derivative of the formula ##STR1## wherein X and X' are the same or different and are hydrogen or alkyl. R and R' are the same or different and are hydrogen, alkyl, hydroxyalkyl or alkanoyl and

Vinyl ethers of nucleoside analogs

Phosphonate nucleoside analogs

Provided are compounds of the following formulae: A phosphonomethoxymethyoxymethyl purine/pyrimidine derivative of the formula ##STR1## wherein X and X' are the same or different and are hydrogen or alkyl. R and R' are the same or different and are hydrogen, alkyl, hydroxyalkyl or alkanoyl; B is a purine or pyrimidine base. optionally R is taken together with X' to complete a cyclic phosphonate having the formula ##STR2## A 4'-phosphonomethoxytetrahydrofuranyl-1'-purine-pyrimidine of the formula ##STR3## wherein X and X' are the same or different and are hydrogen or alkyl, the dashed line is an optional bond, Y and Z are the same or different and are hydrogen, hydroxyl or alkyl or Y+Z are taken together to form an epoxide or cyclopropyl, and B is a purine or pyrimidine base.

Novel cephem derivatives represented by the general formula ##STR1## in which the Acyl substituent is a group of the formula ##STR2## wherein Ar is a lipophilic optionally substituted phenyl, naphthyl, pyridyl or benzthiazolyl group; R.sup.1 is selected from certain optionally substituted aliphatic, aromatic, arylaliphatic or sugar moieties and R.sup.2 and R.sup.3 are each independently hydrogen, alkyl or aminoalkylcarbonylamino are gram-positive antibacterial agents, especially useful in the treatment of infectious diseases caused by methicillin-resistant Staphylococcus aureus (MRSA).

Novel cephem derivatives represented by the general formula ##STR1## in which the Acyl substituent is a group of the formula ##STR2## wherein Ar is a lipophilic optionally substituted phenyl, naphthyl or pyridyl group; R.sup.1 represents either the residue of a heterocyclic amino acid or a C.sub.2 -C.sub.10 alkyl group substituted by both a carboxyl group and a group of the formula --NR.sup.9 R.sup.10 or ##STR3## in which R.sup.9 and R.sup.10 are each independently hydrogen or C.sub.1 -C.sub.6 alkyl, said C.sub.2 -C.sub.10 alkyl group being optionally interrupted by one or more nitrogen atoms or carbonyl groups, and R.sup.2 and R.sup.3 are each independently hydrogen, alkyl or aminoalkyl are gram-positive antibacterial agents, especially useful in the treatment of diseases caused by methicillin-resistant Staphylococcus aureus (also referred to below as MRSA or methicillin-resistant S. aureus).

Substituted 4-thio pyridones

Cephalosporin derviatives

Pyridinium thiomethyl substituted chepholosporin derivatives

Novel cephem derivatives represented by the general formula ##STR1## in which the Acyl substituent is a group of the formula ##STR2## where Ar is a substituted phenyl or optionally substituted naphthyl or benzthiazolyl group and A is a substituted-pyridinium group are gram-positive antibiotics, especially useful in the treatment of diseases caused by methicillin-resistant Staphylococcus aureus.

The present invention concerns nucleotide analogs and their compositions and use. In particular it relates to novel (phosphonomethoxy) methoxy purine/pyrimidine derivatives.

Antiviral (phosphonomethoxy)methoxy purine/pyrimidine derivatives

Thymidine kinase inhibitor of formula I ##STR1## in which R is C.sub.1-6 alkyl or AR(CH.sub.2).sub.n --, wherein Ar represents phenyl optionally substituted with one to five same or different halogen, C.sub.1-6 alkyl or C.sub.1-6 alkyloxy; and n equals one to six. A further aspect of the present invention provides a method of inhibiting viral thymidine kinase. Yet another aspect of the invention relates to treating herpes simplex viral infections in mammals. Yet another aspect of the invention provides a pharmaceutical formulation.

Growing community of inventors

Durham, CT, United States of America

Peter F Misco