examples include asymmetrical 2 - and / or n 6 - substituted - adenosine tetraphosphates and related p 1 , p 4 - dithio , p 2 , p 3 - methylene , - halomethylene , and substituted methylene , and p 1 , p 4 - dithio - p 2 , p 3 - methylene , - halomethylene , and substituted methylene - tetraphosphonates . specific compounds of the invention may also be of formula ia , ii , or iii . the compounds of the invention may be used in the form of the free acid ( or base ) or in the form of salts . the invention also includes all stereoisomeric forms of the compounds . for example , when x and / or x ′ is s , p 1 and / or p 4 may have the r or s configuration . in addition , when y is czz ′, and z and z are not identical , y may also be chiral , if the rest of the molecule is not symmetric . for compounds with x ═ x ′═ s , y ═ o or czz ′ where z and z ′ are the same , four diastereomers with different stereo - configuration at p 1 , and p 4 are possible , namely r p1 r p4 , s p1 s p4 , r p1 s p4 , and s p1 r p4 . if r 2 = r 2 ′, r 6 = r 6 ′, q 1 = q 1 ′, q 2 = q 2 ′, q 3 = q 3 ′, and q 4 = q 4 ′, a meso compound is formed , where the r p1 s p4 and s p1 r p4 configurations are equivalent . when p 1 and p 4 are in different absolute configuration , e . g ., s p1 r p4 or r p1 s p4 , y ═ czz ′, and z differs from z ′, the carbon atom between p 2 and p 3 has two different phosphorous - containing substituents , may be chiral , and may contribute to the formation of additional stereoisomers ( including meso forms when the molecule is otherwise symmetrical ). additional chiral centers are found in the carbon atoms of the five - membered ring containing q 3 and its pendant 5 ′ carbon and potentially in substituents at positions r 2 , r 2 ′, r 6 , and / or r 6 ′. the individual diastereomers can be separated by analytical and preparative reverse phase hplc as described by blackburn and guo ( tetrahedr . lett ., 1990 , 31 ( 30 ): 4371 - 4374 ) or by other methods for separations of stereoisomers known to the one of skill in the art . all such forms , including mixtures , are within the scope of the invention . specific examples of compounds of the invention are listed in table 1 . compounds of the invention may be synthesized according to methods known in the art , with reference to examples provided herein . for example , methods for the synthesis of bis - nucleoside tetraphosphates are described in holler “ the chemistry of dinucleoside polyphosphates ” in ap 4 a and other dinucleoside polyphosphates ; mclennan , a . g . ed . crc press : boca raton , fla ., 1992 , pp 9 - 30 ; blackburn , et al . “ synthetic structural analogues of dinucleoside polyphosphates ” in ap 4 a and other dinucleoside polyphosphates ; mclennan , a . g . ed . crc press : boca raton , fla ., 1992 , pp 305 - 342 ; blackburn and guo tetrahedron lett . 1990 , 31 : 4371 - 4374 ; tarussova et al . bioorg . khim ., 1983 , 9 : 838 - 843 ; and international publication no . wo 2008 / 024169 . methods for synthesis of nucleoside 5 ′- monophosphates and monothiophosphates are described in yoshikawa et al . tetrahedr . lett . 1967 , 50 : 5065 - 5068 and murray and atkinson biochemistry 1968 , 11 : 4023 - 4029 . additional information on various methods for synthesis of modified nucleotides and nucleosides is found in pettit synthetic nucleotides van nostrand , 1972 ; scheit nucleotide analogs wiley , 1980 ; and goodman “ chemical synthesis and transformation of nucleosides ” in paul o . ts &# 39 ; o , j . eisinger ( ed .) basic principles in nucleic acid chemistry , vol . 1 , 1974 , pp 94 - 208 . the compounds of the invention may be employed for the inhibition of platelet aggregation , e . g ., adp - induced aggregation , in vitro or in vivo . diseases and uses benefiting from the inhibition of platelet aggregation include thrombosis , such as venous thrombosis ( deep vein thrombosis , veno - occlusive disease , and hematological conditions ( thrombocythemia or polycythemia )), thrombophlebitis , arterial embolism , coronary and cerebral arterial thrombosis ( associated with unstable angina , coronary angioplasty , and acute myocardial infarction ), unstable angina , myocardial infarction , stroke , transient ischemic event , cerebral embolism , kidney embolisms , pulmonary embolisms , primary arterial thrombotic complications of atherosclerotic disease ( thrombotic stroke , peripheral vascular disease , and myocardial infarction without thrombolysis ), thrombotic complications of interventions of atherosclerotic disease ( associated with angioplasty , percutaneous coronary intervention , endarterectomy ( e . g ., of the carotid artery ), stent placement ( e . g ., in the carotid artery ), and coronary or other vascular graft surgery ), thrombotic complications of surgical or mechanical damage ( tissue salvage following surgical or accidental trauma , reconstructive surgery including skin flaps , and reductive surgery ), mechanically - induced platelet activation ( cardiopulmonary bypass resulting in microthromboembolism ), shunt occlusion ( renal dialysis or plasmapheresis ), thrombosis secondary to vascular damage and inflammation ( vasculitis , arteritis , glomerulonephritis , or organ graft rejection ), indications with a diffuse thrombotic / platelet consumption component ( disseminated intravascular coagulation , thrombotic thrombocytopenic purpura , hemolytic uremic syndrome , heparin - induced thrombocytopenia , or pre - eclampsia / eclampsia ), pathological effects of atherosclerosis and arteriosclerosis ( arteriosclerosis , acute myocardial infarction , chronic stable angina , unstable angina , transient ischemic attacks , strokes , peripheral vascular disease , arterial thrombosis , preeclampsia , embolism , restenosis or abrupt closure following angioplasty , carotid endarterectomy , or anastomosis of vascular grafts ), platelet aggregation and clot formation in blood and blood products during storage , chronic or acute states of hyper - aggregability ( caused by dic , septicemia , surgical or infectious shock , post - operative and post - partum trauma , cardiopulmonary bypass surgery , incompatible blood transfusion , abruptio placentae , thrombotic thrombocytopenic purpura , snake venom or immune diseases ), reocclusion of an artery or vein following fibrinolytic therapy , platelet adhesion associated with extracorporeal circulation , coronary artery disease , peripheral artery disease , and thrombotic complications associated with thrombolytic therapy . the compounds of the invention may be formulated into pharmaceutical compositions for administration to human subjects in a biologically compatible form suitable for administration in vivo or in vitro . accordingly , the present invention provides a pharmaceutical composition including a compound of the invention in admixture with a suitable diluent , carrier , or excipient . in accordance with the methods of the invention , the described compounds or salts thereof may be administered to a patient in a variety of forms depending on the selected route of administration , as will be understood by those skilled in the art . the compounds of the invention may be administered , for example , by oral , parenteral , buccal , sublingual , nasal , rectal , patch , pump , or transdermal administration and the pharmaceutical compositions formulated accordingly . parenteral administration includes intravenous , intraperitoneal , subcutaneous , intramuscular , transepithelial , nasal , intrapulmonary , intrathecal , rectal , and topical modes of administration . parenteral administration may be by continuous infusion over a selected period of time . a compound of the invention may also be administered parenterally . solutions of a compound of the invention can be prepared in water suitably mixed with a surfactant , such as hydroxypropylcellulose . dispersions can also be prepared in glycerol , liquid polyethylene glycols , dmso , and mixtures thereof with or without alcohol , and in oils . under ordinary conditions of storage and use , these preparations may contain a preservative to prevent the growth of microorganisms . conventional procedures and ingredients for the selection and preparation of suitable formulations are described , for example , in remington &# 39 ; s pharmaceutical sciences ( 2003 - 20th edition ) and in the united states pharmacopeia : the national formulary ( usp 24 nf19 ), published in 1999 . the pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions . in all cases the form must be sterile and must be fluid to the extent that it is easily administered via syringe . compositions for nasal administration may conveniently be formulated as aerosols , drops , gels , and powders . aerosol formulations typically include a solution or fine suspension of the active substance in a physiologically acceptable aqueous or non - aqueous solvent and are usually presented in single or multidose quantities in sterile form in a sealed container , which can take the form of a cartridge or refill for use with an atomizing device . alternatively , the sealed container may be a unitary dispensing device , such as a single dose nasal inhaler or an aerosol dispenser fitted with a metering valve which is intended for disposal after use . where the dosage form comprises an aerosol dispenser , it will contain a propellant , which can be a compressed gas , such as compressed air or an organic propellant , such as fluorochlorohydrocarbon . the aerosol dosage forms can also take the form of a pump - atomizer . compositions suitable for buccal or sublingual administration include tablets , lozenges , and pastilles , where the active ingredient is formulated with a carrier , such as sugar , acacia , tragacanth , or gelatin and glycerine . compositions for rectal administration are conveniently in the form of suppositories containing a conventional suppository base , such as cocoa butter . the compounds of the invention may be administered to an animal , e . g ., a human , alone or in combination with pharmaceutically acceptable carriers , as noted above , the proportion of which is determined by the solubility and chemical nature of the compound , chosen route of administration , and standard pharmaceutical practice . the dosage of the compounds of the invention , and / or compositions comprising a compound of the invention , can vary depending on many factors , such as the pharmacodynamic properties of the compound ; the mode of administration ; the age , health , and weight of the recipient ; the nature and extent of the symptoms ; the frequency of the treatment , and the type of concurrent treatment , if any ; and the clearance rate of the compound in the animal to be treated . one of skill in the art can determine the appropriate dosage based on the above factors . the compounds of the invention may be administered initially in a suitable dosage that may be adjusted as required , depending on the clinical response . in general , satisfactory results may be obtained when the compounds of the invention are administered to a human at a daily dosage of between 0 . 05 mg and 3000 mg ( measured as the solid form ). a preferred dose ranges between 0 . 05 - 500 mg / kg , more preferably between 0 . 5 - 50 mg / kg . a compound of the invention can be used alone or in combination with other agents to treat , prevent , and / or reduce the risk of thrombosis or other disorders that benefit from inhibition of platelet aggregation . in combination treatments , the dosages of one or more of the compounds may be reduced from standard dosages when administered alone . in this case , dosages of the compounds when combined should provide a preventive or therapeutic effect . in addition to the above - mentioned therapeutic uses , a compound of the invention can also be used in vitro , e . g ., for the preservation or storage of blood products , and in diagnostic assays , screening assays , and as a research tool . 2 - thioadenosine ( prepared as disclosed in u . s . pat . no . 3 , 989 , 683 ) was s - methylated with 1 . 1 equivalents of methyl iodide in the presence of 1 . 2 equivalents of sodium hydride in anhydrous in n , n - dimethylformamide at room temperature ( step a ). 2 - methylthioadenosine was converted to 2 - methylthioadenosine - 5 ′- monophosphate ( step b ) by the method of yoshikawa et al . ( tetrahedr . lett . 1967 , 6065 - 5068 ). the disodium salt of di -( 1 - imidazolyl ) diphosphonic acid was prepared as disclosed in wo 2008 / 024169 from pyrophosphate and carbonyldiimidazole ( steps c , and d ). bis - triethylammonium salt of 2 - methylthioadenosine - 5 ′- monophosphate ( 179 mg , 0 . 30 mmol ) was dissolved in anhydrous dmf ( 5 ml ), and the solvent was evaporated under high vacuum ( 0 . 2 mm hg ) at 35 ° c . to produce a foam . the residue was dissolved in anhydrous dmf ( 5 ml ) under nitrogen . disodium salt of di -( 1 - imidazolyl ) diphosphonic acid ( 32 . 2 mg , 0 . 1 mmol ) was added to this solution , followed by anhydrous zinc chloride ( 408 . 9 mg , 3 . 0 mmol ). the mixture was protected from moisture , stirred for 30 minutes , and then added to a stirred mixture of chelex ® 100 resin in the sodium form ( 10 ml , sigma - aldrich corp . st . louis , mo .) and 0 . 1 m triethylammonium acetate buffer ( 20 ml , ph 8 ). after stirring for 15 minutes the mixture was filtered , and the resin was washed two times with water ( 10 ml each ). the combined filtrate and washings were loaded on a column of qea - sephadex ® ( 2 . 5 × 30 cm , sigma - aldrich corp . st . louis , mo .) in the triethylammonium form , which was pre - equilibrated with 2 column volumes of 0 . 1 m triethylammonium bicarbonate buffer containing 10 % ( v / v ) acetonitrile . a linear gradient of triethylammonium bicarbonate containing 10 % ( v / v ) acetonitrile , from 0 . 1 to 1 . 5 m for 800 min , was passed through the column at a rate of 3 ml / min . the fractions containing the product were combined and evaporated under vacuum . the residue was re - evaporated three times from methanol ( 50 ml each ), dissolved in methanol ( 0 . 5 ml ) and mixed with a 2 . 0 m solution of sodium perchlorate in acetone ( 5 ml ). the mixture was diluted with acetone ( 15 ml ) and stirred for 2 hours . the white solid was collected by centrifugation , and washed by suspending in acetone ( 20 ml ), centrifugation , and decanting . this acetone washing was repeated two more times , to give , after drying for 6 hours at high vacuum , 68 . 1 mg ( 67 %) of compound 2 . 1 h nmr ( 300 mhz , d 2 o ) δ 8 . 15 ( 2h , s , h - 8 ), 5 . 94 ( 2h , d , j = 5 . 79 hz , h - 1 ′), 4 . 75 - 4 . 68 ( 2h , m , h - 2 ′), 4 . 49 ( 2h , dd , j 1 = 3 . 9 hz , j 2 = 4 . 8 hz , h - 3 ′), 4 . 32 - 4 . 26 ( 2h , m , h - 4 ′), 4 . 23 - 4 . 17 ( 4h , m , h - 5 ′), 2 . 46 ( 6h , s , sch 3 ). 31 p nmr ( 1 h dec ., 121 mhz , d 2 o ), ppm : − 11 . 01 -− 11 . 36 ( m , p 1 + p 4 ), − 22 . 45 -− 22 . 81 ( m , p 2 + p 3 ). electrospray ms in the negative ionization mode : observed , 927 . 2 ( 100 . 0 %), 928 . 1 ( 26 . 3 %), 929 . 1 ( 15 . 9 %), 930 . 1 ( 3 . 9 %), 931 . 1 ( 0 . 9 %); calculated for [ m - h ] − , c 22 h 31 n 10 o 19 p 4 s 2 —, m / e : 927 . 0 ( 100 . 0 %), 928 . 0 ( 30 . 2 %), 929 . 0 ( 17 . 4 %), 930 . 0 ( 4 . 2 %), 931 . 0 ( 1 . 2 %). compound 10 was prepared by the method in example 1 , steps e , and f , as the tetrasodium salt in 63 % yield from 2 - methylthioadenosine - 5 ′- thiomonophosphate as the bis - triethylammonium salt . this compound is a mixture of 3 diastereomers with different stereo - configuration at p 1 , and p 4 , namely r p1 r p4 , s p1 s p4 , and r p1 s p4 , which is equivalent to s p1 r p4 , and thus represents a meso - form . the individual diastereomers can be separated by analytical and preparative reverse phase hplc as described by blackburn and guo ( tetrahedr . lett ., 1990 31 ( 30 ): 4371 - 4374 ). the ratio of the three diastereomers was determined by reverse phase hplc to be 1 : 1 : 2 . the characterization of compound 10 is as follows : 1 h nmr ( 300 mhz , d 2 o ): δ 8 . 24 ( 0 . 5h , s , diast . 1h - 8 ) 8 . 19 ( 0 . 5h , s , diast . 2h - 8 ), 8 . 18 ( 1h , s , diast . 3h - 8 ), 5 . 90 ( 2h , d , j = 5 . 8 hz , h - 1 ′), 4 . 77 - 4 . 64 ( 2h , m , h - 2 ′), 4 . 52 - 4 . 44 ( 2h , m , h - 3 ′), 4 . 30 - 4 . 24 ( 2h , m , h - 4 ′), 4 . 24 - 4 . 15 ( 4h , m , h - 5 ′), 2 . 445 ( 3h , s , diast . 3 sch 3 ), 2 . 435 ( 1 . 5h , s , diast . 1 or 2 sch 3 ), 2 . 427 ( 1 . 5h , s , diast . 2 or 1sch 3 ). 31 p nmr ( 1 h dec ., 121 mhz , d 2 o ), ppm : 43 . 53 - 42 . 94 ( m , p 1 - p 4 ), − 23 . 93 -− 24 . 39 ( m , p 2 + p 3 ). 2 - methylthioadenosine 5 ′- thiomonophosphate was made from 2 - methylthioadenosine and phosphorous thiochloride in pyridine according to the method described by fischer et al . ( j . med . chem ., 1999 , 42 : 3636 - 3646 ) and was isolated in 60 % yield as the bis - triethylammonium salt . all the other starting materials and intermediates were made as in example 1 . synthesis of compound 9 , p 1 , p 4 - bis -( 2 - methylthio - 5 ′- adenosine )- p 2 , p 3 - monochloromethylenetetraphosphate compound 9 was prepared following example 1 , steps e , and f , from 2 - methylthioadenosine 5 ′- monophosphate , which was prepared as in example 1 , and disodium chloromethylenebis -( 1 - imidazolylphosphinic acid ), which was prepared as disclosed in wo 2008 / 024169 from monochloromethylene - bis - phosphonic acid , according to the scheme : monochloromethylene - bis - phosphonic acid was prepared from tetraethyl methylenediphosphonate , which was converted to tetraethyl dichloromethylenediphosphonate with sodium hypochloride as described by vepsäläinen et al . ( journal of the chemical society , perkin transactions 1992 , 2 : 835 - 842 ), then selectively reduced to tetraethyl monochloromethylene - bis - phosphonate with sodium sulfite and hydrolyzed to monochloromethylene - bis - phosphonic acid monopyridinium salt as described by mckenna et al . ( phosphorus sulfur and silicon and the related elements , 1988 , 37 : 1 - 12 ). compound 9 was isolated as the tetrasodium salt in 79 % yield . 1 h nmr ( 300 mhz , d 2 o ): δ 8 . 14 , 8 . 12 ( 2h , s , h - 8 ), 5 . 95 ( 2h , d , j = 5 . 5 hz , h - 1 ′), 4 . 73 - 4 . 67 ( 2h , m , h - 2 ′), 4 . 51 - 4 . 47 ( 2h , m , h - 3 ′), 4 . 28 - 4 . 23 ( 2h , m , h - 4 ′), 4 . 18 ( 1h , t , 2 j p - h = 15 . 0 hz , chcl ), 4 . 21 - 4 . 09 ( 4h , m , h - 5 ′), 2 . 449 , 2 . 445 ( 6h , s , sch 3 ). 31 p nmr ( 1 h dec ., 121 mhz , d 2 o ), ppm : 2 . 30 - 1 . 72 ( m , p 2 + p 3 ), − 10 . 55 -− 11 . 05 ( m , p 1 + p 4 ). electrospray ms in the negative ionization mode : observed , m / z , 959 . 2 ( 100 . 0 %), 960 . 2 ( 33 . 1 %), 961 . 1 ( 50 . 5 %), 962 . 1 ( 13 . 5 %), 963 . 1 ( 6 . 6 %), 964 . 1 ( 1 . 4 %); calculated for [ m - h ] − , c 23 h 32 cln 10 o 18 p 4 s 2 —, m / e : 959 . 0 ( 100 . 0 %), 960 . 0 ( 31 . 2 %), 961 . 0 ( 49 . 4 %), 962 . 0 ( 14 . 3 %), 963 . 0 ( 6 . 8 %), 964 . 0 ( 1 . 6 %). synthesis of compound 17 , p 1 , p 4 - bis -( 2 - methylthio - 5 ′- adenosine )- p 1 , p 4 - dithio - p 2 , p 3 - monochloromethylenetetraphosphate compound 17 was prepared by the method in example 1 , steps e , and f , as the tetrasodium salt in 81 % yield from 2 - methylthioadenosine - 5 ′- thiomonophosphate as the bis - triethylammonium salt , which was prepared as per example 2 , and disodium chloromethylenebis -( 1 - imidazolylphosphinic acid ), which was prepared as per example 3 . this compound is a mixture of 4 diastereomers with different stereo - configuration at p 1 , p 4 , and the carbon atom between p 2 and p 3 . when p 1 and p 4 are in the same absolute configuration , namely r p1 r p4 or s p1 s p4 , the carbon atom between p 2 and p 3 has two equivalent substituents , is pro - chiral , and therefore does not contribute to formation of additional stereo - isomers . when p 1 , and p 4 are in different absolute configuration , namely s p1 r p4 or r p1 s p4 , the carbon atom between p 2 and p 3 has two different substituents , becomes chiral , and contributes to the formation of two additional stereo - isomers . therefore the configuration of the four observed stereo - isomers is : r p1 , r p4 ; s p1 , s p4 ; r p1 , r c , s p4 , which is equivalent to s p1 , r c , r p4 and therefore is a meso form ; and r p1 , s c , s p4 , which is equivalent to s p1 , s c , r p4 , and represents another meso form . here r c , or s c represents the absolute stereo - configuration of the carbon atom between p 2 and p 3 . the four individual diastereomers can be separated by analytical and preparative reverse phase hplc as described in example 2 . the characterization of compound 17 is as follows : 1 h nmr ( 300 mhz , d 2 o ) δ 8 . 35 - 8 . 11 ( multiple s , 2h , h - 8 ), 6 . 09 - 5 . 94 ( m , 2h , h - 1 ′), 4 . 90 - 4 . 35 ( 1h , multiple t , c h — cl ), 4 . 82 - 4 . 70 ( m , 2h , h - 2 ′), 4 . 60 - 4 . 50 ( m , 2h , h - 3 ′), 4 . 37 - 4 . 13 ( m , 6h , h - 4 ′+ h ′ 5 ′), 2 . 53 - 2 . 47 ( ms , 6h , sch 3 ). 31 p nmr ( 1 h dec ., 121 mhz , d 2 o ), ppm : 43 . 15 - 42 . 02 ( m , p 1 + p 4 ), 2 . 00 - 1 . 22 ( m , p 2 + p 3 ). electrospray ms in the negative ionization mode : observed , m / z , 990 . 9 ( 100 . 0 %), 991 . 9 ( 29 . 5 %) 992 . 9 ( 56 . 7 %), 993 . 9 ( 16 . 6 %), 994 . 8 , ( 10 . 0 %); calculated for [ m - h ] − , c 23 h 32 cln 10 o 16 p 4 s 4 , m / e : 990 . 95 ( 100 . 0 %), 991 . 96 ( 32 . 8 %), 992 . 95 ( 57 . 5 %), 993 . 95 ( 17 . 1 %), 994 . 94 ( 11 . 5 %). synthesis of compound 23 , p 1 , p 4 - bis -( 2 - ethylthio - 5 ′- adenosine )- p 1 , p 4 - dithio - p 2 , p 3 - monochloromethylenetetraphosphate compound 23 was made by the methods described in examples 1 - 4 as the tetrasodium salt in 56 % yield from 2 - ethylthioadenosine - 5 ′- thiomonophosphate as the bis - triethylammonium salt and disodium chloromethylenebis -( 1 - imidazolylphosphinic acid ). 2 - ethylthioadenosine - 5 ′- thiomonophosphate was prepared as per example 2 from 2 - ethylthioadenosine , which was prepared by reaction of 2 - thioadenosine with ethyl iodide using the method for synthesis of 2 - methylthioadenosine described in example 1 . compound 23 was prepared as a mixture of 4 diastereomers with different stereo - configuration at p 1 , and p 4 , and the carbon atom between p 2 and p 3 , and which absolute configuration is analogous to the absolute configuration of the stereo - isomers of compound 17 described in example 4 . compound 23 : 1 h nmr ( 300 mhz , d 2 o ) δ 8 . 15 - 8 . 02 ( multiple s , 2h , h - 8 ), 5 . 88 - 5 . 83 ( m , 2h , h - 1 ′), 4 . 78 - 4 . 35 ( 1h , multiple t , c h — cl ), 4 . 67 - 4 . 55 ( m , 2h , h - 2 ′), 4 . 42 - 4 . 35 ( m , 2h , h - 3 ′), 4 . 22 - 4 . 13 ( m , 2h , h - 4 ′), 4 . 13 - 3 . 98 ( m , 4h , h - 5 ′), 3 . 00 - 2 . 86 ( m , 4h , sch 2 ), 1 . 21 - 1 . 12 ( mt , 6h , ch 3 ). 31 p nmr ( 1 h dec ., 121 mhz , d 2 o ), ppm : 44 . 32 - 42 . 78 ( m , p 1 + p 4 ), 2 . 79 - 2 . 12 ( m , p 2 + p 3 ). electrospray ms in the negative ionization mode : observed , m / z , 1019 . 1 ( 100 %), 1020 . 1 ( 38 . 0 %), 1021 . 0 ( 53 . 8 %), 1022 . 0 ( 19 . 5 %), 1022 . 9 ( 11 . 8 %), 1023 . 9 ( 3 . 1 %); calculated for [ m - h ] − , c 25 h 36 cln 10 o 16 p 4 s 4 −, m / e : 1018 . 98 ( 100 . 0 %), 1019 . 99 ( 33 . 0 %), 1020 . 98 ( 59 . 3 %), 1021 . 98 ( 19 . 1 %), 1022 . 98 ( 12 . 0 %), 1023 . 98 ( 2 . 3 %). synthesis of compound 32 , p 1 , p 4 - bis ( 2 - propylthio - 5 ′- adenosine )- p 1 , p 4 - dithio - p 2 , p 3 - monochloromethylenetetraphosphate compound 32 was prepared by the methods described in examples 1 - 4 as the tetrasodium salt in 70 % yield from 2 - propylthioadenosine - 5 ′- thiomonophosphate as the bis - triethylammonium salt and disodium chloromethylenebis -( 1 - imidazolylphosphinic acid ). 2 - propylthioadenosine - 5 ′- thiomonophosphate was prepared as per example 2 from 2 - propylthioadenosine , which was prepared by reaction of 2 - thioadenosine with propyl iodide using the method for synthesis of 2 - methylthioadenosine described in example 1 . compound 32 is a mixture of 4 diastereomers with different stereo - configuration at p 1 , p 4 , and the carbon atom between p 2 and p 3 , and which absolute configuration is analogous to the absolute configuration of the stereo - isomers of compound 17 described in example 4 . compound 32 : 1 h nmr ( 300 mhz , d 2 o ) δ 8 . 29 - 7 . 95 ( multiple s , 2h , h - 8 ), 5 . 89 - 5 . 82 ( m , 2h , h - 1 ′), 4 . 81 - 4 . 31 ( 1h , multiple t , c h — cl ), 4 . 67 - 4 . 55 ( m , 2h , h - 2 ′), 4 . 43 - 4 . 33 ( m , 2h , h - 3 ′), 4 . 24 - 4 . 16 ( m , 2h , h - 4 ′), 4 . 16 - 4 . 00 ( m , 4h , h - 5 ′), 2 . 98 - 2 . 81 ( m , 4h , sch 2 ), 1 . 63 - 1 . 42 ( m , 4h , sch 2 ch 2 ), 0 . 87 - 0 . 78 ( multiple t , 6h , ch 3 ). 31 p nmr ( 1 h dec ., 121 mhz , d 2 o ), ppm : 43 . 8 - 42 . 5 ( m , p 1 + p 4 ), 3 . 1 - 1 . 8 ( m , p 2 + p 3 ). electrospray ms in the negative ionization mode : observed , m / z , 1047 . 0 ( 100 %), 1048 . 0 ( 36 . 7 %), 1048 . 9 ( 55 . 3 %), 1049 . 9 , ( 18 . 4 %), 1050 . 9 , ( 10 . 8 %), 1051 . 9 ( 4 . 6 %); calculated for [ m - h ] − , c 27 h 40 cln 10 o 16 p 4 s 4 —, m / e : 1047 . 0 ( 100 . 0 %), 1048 . 0 ( 37 . 2 %), 1049 . 0 ( 60 . 0 %), 1050 . 0 ( 20 . 5 %), 1051 . 0 ( 12 . 4 %), 1052 . 0 ( 3 . 6 %). synthesis of compound 34 , p 1 , p 4 - bis ( 2 -( 3 , 3 , 3 ,- trifluoropropylthio )- 5 ′- adenosine )- p 1 , p 4 - dithio - p 2 , p 3 - monochloromethylenetetraphosphate compound 34 was made by the methods described in examples 1 - 4 as the tetrasodium salt in 61 % yield from 2 -( 3 , 3 , 3 - trifluoropropylthio ) adenosine - 5 ′- thiomonophosphate as the bis - triethylammonium salt and disodium chloromethylenebis -( 1 - imidazolylphosphinic acid ). 2 -( 3 , 3 , 3 - trifluoropropylthio ) adenosine - 5 ′- thiomonophosphate was prepared as per example 2 from 2 -( 3 , 3 , 3 - trifluoropropylthio ) adenosine , which was prepared by reaction of 2 - thioadenosine with 1 - iodo - 3 , 3 , 3 - trifluoropropane using the method for synthesis of 2 - methylthioadenosine described in example 1 . compound 34 was isolated as a mixture of 4 diastereomers with different stereo - configuration at p 1 , p 4 , and the carbon atom between p 2 and p 3 , and which absolute configuration is analogous to the absolute configuration of the stereo - isomers of compound 17 described in example 4 . compound 34 : 1 h nmr ( 300 mhz , d 2 o ) δ 8 . 27 - 8 . 11 ( multiple s , 2h , h - 8 ), 5 . 98 - 5 . 92 ( m , 2h , h - 1 ′), 4 . 94 - 4 . 41 ( 1h , multiple t , c h — cl ), 4 . 69 - 4 . 61 ( m , 2h , h - 2 ′), 4 . 53 - 4 . 44 ( m , 2h , h - 3 ′), 4 . 32 - 4 . 25 ( m , 2h , h - 4 ′), 4 . 25 - 4 . 12 ( m , 4h , h - 5 ′), 3 . 23 - 3 . 13 ( m , 4h , sch 2 ), 2 . 70 - 2 . 50 ( m , 4h , ch 2 cf 3 ). 31 p nmr ( 1 h dec ., 121 mhz , d 2 o ), ppm : 44 . 1 - 42 . 7 ( m , p 1 + p 4 ), 2 . 98 - 2 . 15 ( m , p 2 + p 3 ). electrospray ms in the negative ionization mode : observed , m / z , 1155 . 1 ( 100 %), 1156 . 16 ( 35 . 8 %), 1157 . 0 ( 55 . 3 %), 1158 . 0 ( 18 . 6 %), 1159 . 0 ( 10 . 3 %), 1160 . 0 ( 3 . %); calculated for [ m - h ] − , c 27 h 34 clf 6 n 10 o 16 p 4 s 4 —, m / e : 1155 . 0 ( 100 . 0 %), 1156 . 0 ( 37 . 1 %), 1157 . 0 ( 60 . 0 %), 1158 . 0 ( 20 . 4 %), 1159 . 0 ( 11 . 1 %), 1160 . 0 ( 3 . 3 %). synthesis of compound 37 , p 1 , p 4 - bis -( 2 - pentylthio - 5 ′- adenosine )- p 1 , p 4 - dithio - p 2 , p 3 - monochloromethylenetetraphosphate compound 37 was made by the methods described in examples 1 - 4 as the tetrasodium salt in 64 % yield from 2 - pentylthioadenosine - 5 ′- thiomonophosphate as the bis - triethylammonium salt and disodium chloromethylenebis -( 1 - imidazolylphosphinic acid ). 2 - pentylthioadenosine - 5 ′- thiomonophosphate was prepared as per example 2 from 2 - pentylthioadenosine , which was prepared by reaction of 2 - thioadenosine with n - pentyl iodide using the method for synthesis of 2 - methylthioadenosine described in example 1 . compound 37 was isolated as a mixture of 4 diastereomers with different stereo - configuration at p 1 , p 4 , and the carbon atom between p 2 and p 3 , and which absolute configuration is analogous to the absolute configuration of the stereo - isomers of compound 17 described in example 4 . compound 37 : 1 h nmr ( 300 mhz , d 2 o ) δ 8 . 26 - 8 . 12 ( multiple s , 2h , h - 8 ), 5 . 98 - 5 . 93 ( m , 2h , h - 1 ′), 4 . 89 - 4 . 39 ( 1h , multiple t , c h — cl ), 4 . 73 - 4 . 64 ( m , 2h , h - 2 ′), 4 . 52 - 4 . 45 ( m , 2h , h - 3 ′), 4 . 32 - 4 . 23 ( m , 2h , h - 4 ′), 4 . 23 - 4 . 11 ( m , 4h , h - 5 ′), 3 . 03 - 2 . 92 ( m , 4h , sch 2 ), 1 . 63 - 1 . 50 ( m , 4h , sch 2 ch 2 ), 1 . 34 - 1 . 12 ( m , 8h , ch 2 ch 2 ch 3 ), 0 . 82 - 0 . 72 ( m , 6h , ch 3 ). 31 p nmr ( 1 h dec ., 121 mhz , d 2 o ), ppm : 44 . 05 - 42 . 83 ( m , p 1 + p 4 ), 2 . 96 - 2 . 13 ( m , p 2 + p 3 ). electrospray ms in the negative ionization mode : observed , m / z , 1103 . 3 ( 100 %), 1104 . 3 ( 43 . 1 %), 1105 . 1 ( 61 . 8 %), 1106 . 1 ( 21 . 8 %), 1107 . 0 ( 11 . 0 %), 1108 . 0 ( 3 . 2 %); calculated for [ m - h ] − , c 31 h 48 cln 10 o 16 p 4 s 4 —, m / e : 1103 . 1 ( 100 . 0 %), 1104 . 1 ( 41 . 6 %), 1105 . 1 ( 61 . 8 %), 1106 . 1 ( 23 . 1 %), 1107 . 1 ( 13 . 3 %), 1108 . 1 ( 4 . 1 %). synthesis of compound 44 , p 1 , p 4 - bis ( 2 - chloro - 5 ′- adenosine )- p 1 , p 4 - dithio - p 2 , p 3 - monochloromethylenetetraphosphate compound 44 was made by the methods described in examples 1 - 4 as the tetrasodium salt in 69 % yield from 2 - chloroadenosine - 5 ′- thiomonophosphate as the bis - triethylammonium salt , and disodium chloromethylenebis -( 1 - imidazolylphosphinic acid ). 2 - chloroadenosine - 5 ′- thiomonophosphate was prepared as per example 2 from 2 - chloroadenosine ( sigma - aldrich , st . louis , mo .). compound 44 was isolated as a mixture of 4 diastereomers with different stereo - configuration at p 1 , p 4 , and the carbon atom between p 2 and p 3 , and which absolute configuration is analogous to the absolute configuration of the stereo - isomers of compound 17 described in example 4 . compound 44 : 1 h nmr ( 300 mhz , d 2 o ) δ 8 . 39 - 8 . 26 ( multiple s , 2h , h - 8 ), 5 . 91 - 5 . 86 ( m , 2h , h - 1 ′), 4 . 90 - 4 . 39 ( 1h , multiple t , c h — cl ), 4 . 70 - 4 . 61 ( m , 2h , h - 2 ′), 4 . 53 - 4 . 46 ( m , 2h , h - 3 ′), 4 . 36 - 4 . 27 ( m , 2h , h - 4 ′), 4 . 27 - 4 . 11 ( m , 4h , h - 5 ′). 31 p nmr ( 1 h dec ., 121 mhz , d 2 o ), ppm : 43 . 75 - 42 . 42 ( m , p 1 + p 4 ), 2 . 63 - 1 . 95 ( m , p 2 + p 3 ). electrospray ms in the negative ionization mode : observed , m / z , 967 . 0 ( 92 . 2 %), 968 . 0 ( 27 . 0 %), 969 . 0 ( 100 . 0 %), 970 . 0 ( 28 . 9 %), 971 . 0 ( 42 . 0 %), 972 . 0 ( 10 . 3 %), 973 . 0 ( 8 . 6 %), 973 . 9 ( 1 . 8 %); calculated for [ m - h ] − , c 21 h 26 cl 3 n 10 o 16 p4s 2 —, m / e : 966 . 9 ( 89 . 1 %), 967 . 9 ( 25 . 8 %), 968 . 9 ( 100 . 0 %), 969 . 9 ( 28 . 1 %), 970 . 9 ( 42 . 3 %), 971 . 9 ( 11 . 4 %), 972 . 9 ( 8 . 3 %), 973 . 9 ( 2 . 1 %). synthesis of compound 40 , p 1 , p 1 - bis -( 2 - iodo - 5 ′- adenosine )- p 1 , p 4 - dithio - p 2 , p 3 - monochloromethylenetetraphosphate compound 40 was prepared by the methods in examples 1 - 4 as the tetrasodium salt in 73 % yield from 2 - iodoadenosine - 5 ′- thiomonophosphate as the bis - triethylammonium salt , and disodium chloromethylenebis -( 1 - imidazolylphosphinic acid ). 2 - iodoadenosine - 5 ′- thiomonophosphate was prepared as per example 2 from 2 - iodoadenosine ( sigma - aldrich , st . louis , mo .). compound 40 was isolated as a mixture of 4 diastereomers with different stereo - configuration at p 1 , p 4 , and the carbon atom between p 2 and p 3 , and which absolute configuration is analogous to the absolute configuration of the stereo - isomers of compound 17 described in example 4 . compound 40 : 1 h nmr ( 300 mhz , d 2 o ) δ 8 . 38 - 8 . 16 ( multiple s , 2h , h - 8 ), 5 . 89 - 5 . 84 ( m , 2h , h - 1 ′), 4 . 93 - 4 . 39 ( 1h , multiple t , c h — cl ), 4 . 64 - 4 . 57 ( m , 2h , h - 2 ′), 4 . 52 - 4 . 45 ( m , 2h , h - 3 ′), 4 . 34 - 4 . 27 ( m , 2h , h - 4 ′), 4 . 27 - 4 . 14 ( m , 4h , h - 5 ′). 31 p nmr ( 1 h dec ., 121 mhz , d 2 o ), ppm : 43 . 95 - 42 . 45 ( m , p 1 + p 4 ), 3 . 13 - 2 . 02 ( m , p 2 + p 3 ). electrospray ms in the negative ionization mode : observed , m / z , 1151 . 0 ( 100 . 0 %), 1152 . 0 ( 29 . 7 %), 1152 . 9 ( 46 . 2 %), 1153 . 9 ( 13 . 7 %), 1154 . 9 ( 5 . 8 %), 1155 . 9 ( 1 . 3 , %); calculated for [ m - h ] − , c 21 h 26 cli 2 n 10 o 16 p 4 s 2 —, m / e : 1150 . 8 ( 100 . 0 %), 1151 . 8 ( 28 . 9 %), 1152 . 8 ( 48 . 3 %), 1153 . 8 ( 13 . 1 %), 1154 . 8 ( 6 . 3 %), 1155 . 8 ( 1 . 4 %). synthesis of compound 22 , p 1 , p 4 - bis ( n 6 - methyl - 2 - methylthio - 5 ′- adenosine )- p 1 , p 4 - dithio - p 2 , p 3 - monochloromethylenetetraphosphate compound 22 was prepared by the methods in examples 1 - 4 as the tetrasodium salt in 72 % yield from n 6 - methyl - 2 - methylthioadenosine - 5 ′- thiomonophosphate and disodium chloromethylenebis -( 1 - imidazolylphosphinic acid ). n 6 - methyl - 2 - methylthioadenosine - 5 ′- thiomonophosphate was prepared as per example 2 from n 6 - methyl - 2 - methylthioadenosine . n 6 - methyl - 2 - methylthioadenosine was prepared from 2 - methylthioadenosine using the method of ingall et al . ( j . med . chem . 1999 42 : 213 - 220 ), according to the scheme : compound 22 was isolated as a mixture of 4 diastereomers with different stereo - configuration at p 1 , p 4 , and the carbon atom between p 2 and p 3 , and which absolute configuration is analogous to the absolute configuration of the stereo - isomers of compound 17 described in example 4 . compound 40 : 1 h nmr ( 300 mhz , d 2 o ) δ 8 . 10 - 7 . 90 ( 2h , ms , h - 8 ), 5 . 90 - 5 . 83 ( 2h , md , h - 1 ′), 5 . 03 - 4 . 35 ( 1h , mt , c h — cl ), 4 . 75 - 4 . 63 ( 2h , m , h - 2 ′), 4 . 52 - 4 . 43 ( 2h , m , h - 3 ′), 4 . 29 - 4 . 21 ( 2h , m , h - 4 ′), 4 . 21 - 4 . 02 ( 4h , m , h - 5 ′), 2 . 88 - 2 . 71 ( 6h , ms , sch 3 ), 2 . 40 - 2 . 25 ( 6h , ms , nch 3 ). 31 p nmr ( 1 h dec ., 121 mhz , d 2 o ), ppm : 41 . 96 - 40 . 32 ( m , p 1 - p 4 ), 0 . 69 -− 0 . 16 ( m , p 2 + p 3 ). electrospray ms in the negative ionization mode : observed , 1019 . 0 ( 100 . 0 %), 1020 . 0 ( 36 . 6 %), 1020 . 9 ( 53 . 8 %), 1021 . 9 ( 18 . 0 %), 1022 . 9 ( 11 . 3 %); calculated for [ m - h ] − , c 25 h 36 cln 10 o 16 p 4 s 4 − : 1019 . 0 ( 100 . 0 %), 1020 . 0 ( 35 . 0 %), 1021 . 0 ( 59 . 3 %), 1022 . 0 ( 19 . 2 %), 1023 . 0 ( 12 . 0 %) synthesis of compound 12 , p 1 , p 4 - bis -( n 6 - propyl - 5 ′- adenosine )- p 1 , p 4 - dithio - p 2 , p 3 - monochloromethylenetetraphosphate compound 12 was made by the methods described in examples 1 - 4 as the tetrasodium salt in 69 % yield from n 6 - propyladenosine - 5 ′- thiomonophosphate as the bis - triethylammonium salt , and disodium chloromethylenebis -( 1 - imidazolylphosphinic acid ). n 6 - propyladenosine - 5 ′- thiomonophosphate was prepared as per example 2 from n 6 - propyladenosine . n 6 - propyladenosine was prepared from inosine and n - propylamine according to the method of wan et al . ( org . lett ., 2005 , 7 : 5877 - 5880 ). compound 12 was isolated as a mixture of 4 diastereomers with different stereo - configuration at p 1 , p 4 , and the carbon atom between p 2 and p 3 , and which absolute configuration is analogous to the absolute configuration of the stereo - isomers of compound 17 given in example 4 . compound 12 : 1 h nmr ( 300 mhz , d 2 o ) δ 8 . 38 - 8 . 19 ( 2h , multiple s , h - 8 ), 7 . 95 - 7 . 90 ( multiple s , 2h , h - 2 ), 5 . 98 - 5 . 91 ( 2h , m , h - 1 ′), 4 . 98 - 4 . 42 ( 1h , multiple t , c h — cl ), 4 . 77 - 4 . 64 ( 2h , m , h - 2 ′), 4 . 55 - 4 . 47 ( 2h , m , h - 3 ′), 4 . 36 - 4 . 27 ( 2h , m , h - 4 ′), 4 . 27 - 4 . 09 ( 4h , m , h - 5 ′), 3 . 30 - 3 . 11 ( 4h , multiple b s , nch 2 ), 1 . 61 - 1 . 46 ( m , 4h , nch 2 ch 2 ), 0 . 92 - 0 . 83 ( m , 6h , ch 3 ). 31 p nmr ( 1 h dec ., 121 mhz , d 2 o ), ppm : 44 . 02 - 42 . 41 ( m , p 1 + p 4 ), 2 . 97 - 2 . 03 ( m , p 2 + p 3 ). electrospray ms in the negative ionization mode : observed , 983 . 1 ( 100 . 0 %), 984 . 1 ( 33 . 6 %), 985 . 1 ( 48 . 3 %), 986 . 1 ( 15 . 0 %), 987 . 0 ( 6 . 9 %), 988 . 1 ( 1 . 5 %); calculated for [ m - h ] − , c 27 h 40 cln 10 o 16 p 4 s 2 —, m / e : 983 . 1 ( 100 . 0 %), 984 . 1 ( 35 . 6 %), 985 . 1 ( 50 . 4 %), 986 . 1 ( 16 . 4 %), 987 . 1 ( 7 . 3 %), 988 . 1 ( 1 . 9 %) synthesis of compound 8 , p 1 , p 4 - bis ( n 6 - methyl - 5 ′- adenosine )- p 1 , p 4 - dithio - p 2 , p 3 - monochloromethylenetetraphosphate compound 8 was prepared following example 12 , using methylamine , instead of n - propylamine . the product was isolated as the tetrasodium salt in 66 % yield , and consisted of 4 diastereomers with different stereo - configuration at p 1 , p 4 , and the carbon atom between p 2 and p 3 , and which absolute configuration is analogous to the absolute configuration of the stereo - isomers of compound 17 given in example 4 . compound 8 : 1 h nmr ( 300 mhz , d 2 o ) δ 8 . 38 - 8 . 16 ( 2h , ms , h - 8 ), 7 . 98 - 7 . 92 ( ms , 2h , h - 2 ), 5 . 98 - 5 . 91 ( 2h , m , h - 1 ′), 5 . 03 - 4 . 42 ( 1h , mt , c h — cl ), 4 . 77 - 4 . 68 ( 2h , m , h - 2 ′), 4 . 55 - 4 . 47 ( 2h , m , h - 3 ′), 4 . 37 - 4 . 29 ( 2h , m , h - 4 ′), 4 . 29 - 4 . 08 ( 4h , m , h - 5 ′), 2 . 90 - 2 . 82 ( 6h , ms , nch 3 ). 31 p nmr ( 1 h dec ., 121 mhz , d 2 o ), ppm : 43 . 97 - 42 . 43 ( m , p 1 ′+ p 4 ), 3 . 03 - 1 . 92 ( m , p 2 + p 3 ). electrospray ms in the negative ionization mode : observed , 927 . 1 ( 100 . 0 %), 928 . 1 ( 31 . 9 %), 929 . 1 ( 47 . 0 %), 930 . 1 ( 19 . 3 %), 931 . 0 ( 8 . 1 %); calculated for [ m - h ] − , c 23 h 32 cln 10 o 16 p 4 s 2 —, m / e : 927 . 0 ( 100 . 0 %), 929 . 0 ( 49 . 0 %), 928 . 0 ( 31 . 1 %), 930 . 0 ( 14 . 2 %), 931 . 0 ( 6 . 6 %). platelet aggregation was initiated by adding adp ( 3 μm ) in the presence or absence of various concentrations of test compound to platelet - rich human plasma , and the aggregation response was recorded for six minutes in a chrono - log ® aggregometer running the aggro / link software ( chrono - log ®, havertown , pa .). potency of example compounds to inhibit platelet aggregation is shown in table 2 . the methods of sturgeon et al . ( j . pharm . toxicol . meth . 53 : 20 - 29 , 2006 ) are used to test the antithrombotic activity of compounds in mice , rats , and rabbits . the method of folts ( circulation 83 ( suppl iv ): 3 - 14 , 1991 ) is used to test the antithrombotic activity of compounds in dogs . all publications , patent applications , patents , and other documents cited herein are incorporated by reference in their entirety . in case of conflict , the present specification , including definitions , will control . in addition , the materials , methods , and examples are illustrative only and not intended to be limiting . other variations and embodiments of the invention described herein will now be apparent to those of ordinary skill in art without departing from the scope of the invention or the spirit of the claims below .