http://rdf.ncbi.nlm.nih.gov/pubchem/patent/GB-1384611-A
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_5922cbe7c65a9136f85906fa09e7c967 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07H19-06 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07H19-16 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07H19-16 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07H19-06 |
| filingDate | 1972-06-16-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationDate | 1975-02-19-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | GB-1384611-A |
| titleOfInvention | 4,-fluoro nucleosides intermediates and methods of preparaing same |
| abstract | 1384611 4-Fluoro-nucleosides and nucleotides SYNTEX CORP 16 June 1972 [16 June 1971 31 May 1972] 28293/72 Headings C2C and C2P Novel compounds selected from the formulµ wherein R<SP>1</SP> and R<SP>2</SP> are independently hydroxy or aoyloxy having from 2 through 12 carbon atoms, or R<SP>1</SP> and R<SP>2</SP> together form the group wherein R<SP>3</SP> and R<SP>4</SP> are independently hydrogen, lower alkyl, aryl or together with the carbon atom to which they are joined form a cycloalkyl group having from 5 through 7 ring carbon atoms; A<SP>1</SP> is -CH 2 OH, -CH 2 N 3 , -CH 2 I or -CH 2 OPO(OH) 2 ; and B<SP>1</SP> is a purine base selected from 6-mercaptopurine, 2-amino-6- lower alkyl thiopurine, 6-lower alkyl thiopurine, 2 - amino - 6 - mercaptopurine, 6 - methylaminopurine, 6 - dimethyl - aminopurine, 2- amino - 6 - methylaminopurine, 2 - amino - 6- dimethylaminopurine, 6 - (1 - adamantylamino)- purine, 7 - deazaadenine, hypoxanthine, xanthine, guanine, 8-azaguanine, 7-deazaguanine, adenine, 2-flaoroadenine, 2-chloroadenine, 2 -azaadenine, 8 - aza - 9 - deazaadenine, 7 - deaza - 7 - cyanoadenine, and 8 - azaadenine; or B<SP>1</SP> is a pyrimidine base selected from those listed for B<SP>2</SP> below and also 5-bromocytosine, 5-iodocytosine, 5-nitrocytosine, 2-thiocytosine, 5-bromouraeil, 5-iodouracil, 5-nitrouracil, 2-thiouracil, 4-thiouracil, 2,4-dithiouracil, 4-hydroxylamino-5-bromo (or 5-iodo, or 5-nitro) pyrimidin-2-one, or 4-hydroxylaminopyrimidin-2-thione, A<SP>2</SP> is -CH 3 or -CH 2 CH 2 ; and B<SP>2</SP> is a purine base selected from 6-methylaminopurine, 6 - dimethylaminopurine, 2- amino - 6 - methylaminopurine, 2 - amino - 6- dimethylaminopurine, 6 - (1 - adamantylamino)- purine, 7 - deazaadenine, hypoxanthine, xanthine, guanine,. 8-azaguanine, 7-deazaguanine, adenine, 2-fluoroadenine, 2-chloroadenine, 2 - azaadenine, 8 - aza - 9 - deazaadenine, 7 - deaza - 7 - cyanoadenine, and 8 - azaadenine; or B<SP>2</SP> is a pyrimidine base selected from cytosine, 5 - fluorocytosine, 5 - chlorocytosine, 5 - lower alkyl cytosine, 5 - trifluoromethylcytosine, 5 - hydroxymethylcytosine, 5- azacytosine, 6 - azacytosine, 5 - methyl - 6- azacytosine, uracil, 5-fluorouraoil, 5-chlorouracil, 5-lower alkyluracil, 5-trifluoromethyluracil, 5 - hydroxymethyluracil, 5 - azauracil, 6 - azauracil, 5 - methyl - 6 - azauracil, 5- aminouracil, 5 - methylaminouracil, 5 - dimethylaminouracil, 5 - methylaminocytosine, 5 - dimethylaminocytosine, 5 - aminocytosine, 4 - hydroxylamino - 5 - fluoro - pyrimidin - 2- one, 4 - hydroxylamino - 5 - chloro - pyrimidin- 2 - one, 4 - hydroxylamino - 5 - lower alkyl pyrimidin - 2 - one, 4 - hydroxylamino - 5- hydroxymethyl - pyrimidin - 2 - one, 4 - hydroxylamino - 5 - aza - pyrimidin - 2 - one, 4- hydroxylamino - 6 - aza - pyrimidin - 2 - one, 4- hydroxylamino - 5 - methyl - 6 - aza - pyrimidin- 2 - one, 4 - hydroxylamino - 5 - trifluoromethylpyrimidin - 2 - one, and 4 - hydroxylaminopyrimidin-2-one; A<SP>3</SP> is wherein R<SP>11</SP> and R<SP>111</SP> are independently hydrogen or lower alkyl having from 1 through 6 carbon atoms; and B<SP>3</SP> is a purine base selected from those listed for B<SP>1</SP> (except hypoxanthine and adenine); or B<SP>3</SP> is a pyrimidine base selected from the same group of pyrimidine bases as B<SP>1</SP>; wherein A<SP>4</SP> is -CH 2 OH, -CH 2 I, -CH 2 N 3 , -CH 2 OPO(OH) 2 or wherein R<SP>11</SP> and R<SP>111</SP> are as defined above; B<SP>4</SP> is a pyrimidine base selected from cytosine, 5- fluorocytosine, 5-chlorocytosine, 5-bromocytosine, 5 - iodocytosine, uracil, 5 - fluorouracil, 5 - chlorouracil, 5 - bromouracil, 5 - iodouracil, 5-lower alkyl uracil; and R<SP>5</SP> is hydroxy or an acyloxy group having from 2 through 12 carbon atoms; and B<SP>5</SP> is a pyrimidine base selected from cytosine, 5-fluorocytosine, 5-chlorocytosine, uracil, 5-fluorouracil, 5-chlorouracil, and 5- lower alkyl uracil. Compounds of Formula (I) or (XV) where A<SP>1</SP> or A<SP>4</SP> is -CH 2 I can be obtained by treating a compound of one of the formulas (where B<SP>1</SP>(Ac) is a pyrimidine or pure base moiety in which the free amino groups and ring N atoms at position 1 are protected by C 2-12 acyl groups and B<SP>4</SP>(Ac) is an acyl-protected pyrimidine base moiety) with iodine fluoride under reactive conditions in an inert organic solvent. The products can be reacted with a suitable azide reagent to form corresponding 5-azido compounds, which can in turn be reacted with NOBF 4 or by photolysis to yield compounds in which A<SP>1</SP> or A<SP>4</SP> is -CH 2 OH. The latter can be converted to corresponding 5-phosphate or 5 - O - sulphamoyl derivatives. The 5-deoxy-4<SP>1</SP>- fluoro nucleoside of Formula II (A<SP>2</SP> = CH 3 ) are obtained by reduction of the 5-iodo compounds (I) (where A<SP>1</SP> =-CH 2 I), e.g. with catalytic hydrogen, preferably while the 2 and 3 positions are protected with o-alkylidene. The 5-amino compounds of Formula II (A<SP>2</SP> is -CH 2 NH 2 ) are obtained by reduction of compounds I (where A<SP>1</SP> is -CH 2 N 3 ). Examples also describe the preparation of intermediates as follows. Compounds in which free ammo groups in the base moiety of 2,3-O- isopropylidene purine or cytidine nucleosides are obtained by reacting with benzoyl chloride acetic anhydride. 5<SP>1</SP>-O-Methanesulphonyl nucleosides are obtained by reacting corresponding 5<SP>1</SP>-unprotected nucleosides with methane sulphonyl chloride. 4<SP>1</SP>,5<SP>1</SP>-unsaturated nucleosides are obtained by treating the 5<SP>1</SP>-O-mesyl nucleoside with potassium t-butoxide. Pharmaceutical compositions comprising compounds of Formulµ I, II, III, XV and XVI together with an acceptable carrier exhibit various activities ranging from antimetabolite activity, tripanocidal and antibacterial activity, antiviral activity and platelet aggregation inhibition. |
| isCitedBy | http://rdf.ncbi.nlm.nih.gov/pubchem/patent/EP-0304889-A3 http://rdf.ncbi.nlm.nih.gov/pubchem/patent/EP-0304889-A2 |
| priorityDate | 1971-06-16-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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Total number of triples: 163.