Nyegaard & Co A/s

Nycomed Imaging As

C10 Pharma As

Solvell As

Kjell Undheim

Jo Klaveness

Tore Benneche

Mikkel J Gacek

Peter Kremminger

Solvi Gunnes

Meinolf Lange

Per Strande

Magne Solbakken

Michael Hartmann

Janis Vasilevskis

Jessie Sandosham

Soren Laland

Reidar Oftebro

Geir Langli

Michel Gacek

Mioara Andrei

Rolf W Sandnes

Erik Agner

Gunnar A Ulsaker

Vidar BJØRNSTAD

Kjetil Taskén

This invention relates to a process for the preparation of an (Rp)-8-substituted adenosine-3',5&#x2032;-cyclic phosphorothioic acid, or a salt or ester thereof, which comprises P-amidating 8-bromoadenosine-3&#x2032;,5&#x2032;-cyclic phosphoric acid, and reacting the P-amidate with a base and with carbon disulphide to yield (Rp)-8-bromoadenosine-3&#x2032;,5&#x2032;-cyclic phosphorothioic acid or a salt or ester thereof.

Process for the preparation of an (RP)-8-substituted cAMPS

Disclosed herein are 10-desmethyl, 10 substituted-macrolides, their preparation, pharmaceutical compositions containing them, their use and methods of treatment using them. The 10-desmethyl macrolides are particularly useful as antibiotics.

10-substituted macrolide antibiotics

Double-chain hemoregulatory peptides

Single chain peptide compounds having hemoregulatory activity

Double chain peptide compounds having hemoregulatory activity

The present invention provides a synthetic route for tetraazacycloalkane preparation which facilitates heteropoly-N-alkylation of the macrocyclic product, and is thereby beneficial for the production of chelating agents and chelates useful in diagnostic imaging. The process involves (i) reacting a tetraazaalkane with a bridging agent to couple four amine nitrogens of said tetraazaalkane to a bridging moiety to yield a fused tricyclic intermediate, (ii) reacting said intermediate to introduce an alkylene bridge between the secondary amine nitrogens in the outer rings of the fused tricyclic intermediate, optionally by decoupling an alkanediylidene bridging moiety from the tertiary amine nitrogens at the ring fusion sites of the fused tricyclic intermediate, and (iii) where necessary, decoupling said bridging moiety to yield a macrocyclic tetraazacycloalkane.

Process for tetraazacycloalkane preparation

Compounds of the general formula: ##STR1## wherein X represents a halogen atom or a trifluoromethyl group;

Substituted pyrimidin-2-ones and the salts thereof

Compounds of the general formula: ##STR1## (wherein X represents a halogen atom or a trifluoromethyl group;

Compounds of the general formula: ##STR1## wherein X represents halogen or trifluoromethyl;

Compounds of general formula: ##STR1## (wherein X represents a halogen atom or a trifluoromethyl group; R.sup.1 and R.sup.2, which may be the same or different, each represents a hydrogen atom, or a C.sub.1-4 alkyl group, and R.sup.3 represents a hydrogen atom or a C.sub.1-5 saturated or unsaturated, straight or branched acyclic aliphatic group; a C.sub.3-8 saturated or unsaturated cyclic aliphatic group; a heterocyclic substituted aliphatic group; an araliphatic group; or a heterocyclic or carbocyclic aryl group; any of said groups optionally carrying one or more substituents selected from halogen, oxo, hydroxy, mercapto, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkanoyloxy and amino) and, where an acidic or basic group is present, physiologically compatible salts thereof have been found to be of use in combating abnormal cell proliferation. The compounds of formula I may be prepared by reaction of a 5-halo- or 5-trifluoromethyl-pyrimidin-2-one with an appropriate isocyanate.

Substituted pyrimid-2-ones, the salts thereof, processes for their

Compounds of the formula ##STR1## (wherein X represents a halogen atom; n is 0, 1 or 2; R.sup.1 and R.sup.2, which may be the same or different, each represents a hydrogen atom or a carboxyl, esterified carboxyl, amido or mono- or di-C.sub.1-4 alkylamido group or a C.sub.1-4 alkyl group which may if desired carry a carboxyl or esterified carboxyl group; and R.sup.3 represents a C.sub.1-32 saturated or unsaturated, straight or branched, cyclic or acyclic aliphatic group or an araliphatic or heterocyclic substituted aliphatic group, a heterocyclic group or an aryl group which groups may if desired carry one or more substituents selected from halogen atoms and oxo, nitro, hydroxy, etherified hydroxy, esterified hydroxy, primary, secondary or tertiary amino, acylamino etherified mercapto or S.dbd.O or --SO.sub.2 derivatives thereof and esterified phosphonic acid groups) and, where an acidic or basic group is present, physiologically compatible salts thereof have been found to be of use in combating abnormal cell proliferation. The compounds are prepared inter alia by oxidation of the corresponding sulfide, displacement of a leaving atom or group from the 2-position of the pyrimidine by reaction with a sulfinic acid or by ring closure of the pyrimidine ring.

Pyrimidine-2-sulphides and their S-oxides for use in medicine and

Compounds of the formula: ##STR1## wherein X represents a halogen atom;

5-Halo-pyrimidin-2-ones, the salts thereof

Novel derivatives of pyrimid-2-one having interesting pharmacological properties are described. The compounds of the invention have been found to be of use in the control of, and in particular in the inhibition of the metaphase of malignant tumours and leukaemias. Processes for the preparation of the novel compounds and pharmaceutical compositions containing them are also described.

5-Halopyrimid-2-ones

Antimicrobial compositions comprising as active ingredient at least one compound of the general formula ##STR1## (wherein R.sup.1 and R.sup.5, which may be the same or different each represent a hydrogen or halogen atom and R.sup.2, R.sup.3 and R.sup.4 which may be the same or different, each represent a hydrogen atom or a lower alkyl group) in association with an antimicrobial carrier, excipient or diluent. The compounds of formula I may be prepared by reacting a corresponding dihydrothiazolo 8-oxide compound with a base. Certain of the compounds of formula I are novel and may also be prepared by pyrolytic decarboxylation of a corresponding carboxyl substituted thiazolo-8-oxide compound.

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Oslo, Norway

Kjell Undheim