CA2296665C - Triazolo[4,5-d]pyrimidine derivatives as anti-thromobotic agents - Google Patents

Abstract

The invention provides new tria-zolo[4,5-d]pyrimidine compounds of formula (I), their use as medicaments, compositions containing them and processes for their preparation.

Description

TRIAZOLO[4,5-D]PYRIMIDINE DERIVATIVES AS ANTI-THROMBOTIC AGENTS
The present invention provides new triazolo[4,_5-d]pyrimidine compounds, their use as medicaments, compositions containing them and processes for their preparation.

Platelet adhesion and aggregation are initiating events in arterial thrombosis. Althouah the process of platelet adhesion to the sub-endothelial surface may have an important role to play in the repair of dama~ed vessel walls, the platelet aggreQation that this initiates can precipitate acute thrombotic occlusion of vital vascular beds, leading to events with hi~h morbidity such as myocardial infarction and unstable angina. The success of interventions used to prevent or alleviate these conditions, such as thrombolysis and angioplasty is also comprornised bv platelet mediated occlusion or re-occlusion.

A number of converQing pathways lead to platelet aggregation. Whatever the initial is stimulus, the final common event is a cross linkin; of platelets by binding of fibrinogen to a membrane bindin8 site, glycoprotein IIb/IIIa (GPIIb/IIIa). The hi~h anti-platelet efficacy of antibodies or antagonists for GPIIb/IIIa is explained by their interference with this final common event. However, this efficacy may also explain the bleeding problems that have been observed with this class of a~ent. Thrombin can produce platelet a~oregation laraely independently of other pathways but substantial quantities of thrombin are unlikely to be present without prior activation of platelets by other mechanisms. Thrombin inhibitors such as hirudin are hiahly effective anti-thrombotic agents, but again may produce excessive bleeding because they function as both anti-platelet and anti-coaaulant aQents (The TIMI 9a Investigators (1994), Circulation 90, pp. 1624-1630; The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIa Investigators (1994) Circulation 90, pp. 1631-1637; Neuhaus K.L. et. al. (1994) Circulation 90, pp.1638-1642).

It has been found that ADP acts as a key mediator of thrombosis. A pivotal role for ADP is supported by the fact that other agents, such as adrenaline and 5-hydroxytryptamine (SHT, serotonin) will only produce aggregation in the presence of ADP. The lirnited anti-thrombotic effieacv of aspirin may reflect the fact that it blocks only one source of ADP
which is that released in a thromboxane-dependent manner following platelet adhesion (see e.g. Antiplatelet Trialists' Collaboration (1994), Br. lLied. J 308, pp..81-106; Antiplatelet Trialists'Collaboration (1994), Br. i11ed. J. 308, 7p.159-168). Aspirin has no cffect on 2s aQ-regation produced by other sources of ADP, such as damaQed cells or ADP
released under conditions of turbulent blood flow. ADP-induced platelet aggegation is mediated by the P2rreceptor subtype uniquely located on the platelet membrane. Recently it has been shown that antagonists at this receptor offer significant improvements over other anti-thrombotic agents. Accordingly there is a need to find P27-antagonists as anti-thrombotic agents.
It has now been found that a series of triazolo[4,5-d]pyrirnidine derivatives are PZT-receptor antagonists. In a first aspect the invention therefore provides a compound of formula (I):

N=N

R N

SRI (I) wherein:
R1 is a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8-cycloalkyl or a phenyl group, each group being optionally F~ubstituted by one or more substituents selected from halogen, OR8, NR9 R10, SRi I or C1-6 alkyl (itself optionally substituted by one or more halogen atoms);
R2 is C 1-8 alkyl optionally substituted by one or more substituents selected from halogen, OR 8, NRyRI0, SRC3-8-cycloalky:, aryl (optionally substituted by one or more alkyl groups and/or halogen atoms), or C1-6-alkyi; or RZ :s a C3-8-cycloalkyl group optionally substituted by one or .niore substituents selected from halogen, flRfi, NR9R
10, SR i l Cj-6-alkyl or phenyl, the latter two groups being optionall,r substituted by one or more substituents selected from haloge._, NO2, C(O)Rg, ORg, S!R11 . N.R12R13 a fused 5- or 6-me.n:bered saturated ring containing one or two oxygen atoms, phenyl or Cj_6-alkyl the latter two groups being optionally substituted by ORg, NR9R 10 or one or more haloge:l atoms;
~
one of R3 and R4 is hydroxy and the other is hydrogen, hydroxy or NR9R10 R is a group (CR5 Rb)n,ORi where m is 0 or 1, R5 and R are independently hydrogen, C1-6 alkyl or phenyl the latter two groups being optionally substituted by halogen, and R~
is hydrogen, Ct-6 alkyl or (CRSR6)õR1ijwhere RS and 2 are as deffi-ied above, n is 1 to 3 and Rl4t is COOH, OR15, NRtSR0 or CONR16R1';
or R is a C1,.4 alkyl or C2-4 alkenyl group, each. of which is substituted by one or more ryU
groups selected from =S, =O, =NR" or OR21 and optionally substituted bv one or more grouPs selected from halogen, Ci-4 alkyl, phenyl, SR21, NO2 or NR22R23 (where R21, R22 -and R23 are independently hydrogen, Ci-4 alkyl or phenyl; RG0 is OR24 or NR25R26, where R24 is hydrogen, C1-4 alkyl or phenyl, and R25 and R26 are independently hydrogen, C1-4 alkyl, aryl, C1-6 acyl, arylsulphonyl or arylcarbonyl);
s R8 is hjdrogen, C1-6 alkyl optionally substituted by halogen or R8 is phenyl T:litionally substituted by one or more substituents selected from halogen, N42, C(O)R6, OR6, SR9, NR10R11;

R9, R10 and Ri i are independently hydrogen or Cl-<; alky-;
R12 and R13 are independently hydrogen, C' -6 alkyl, acyl, a.lk-,-l sulfonyl optionally substituted by halogen, or phenyl sulfonyl optionally substi.tu."-Id by C1-C4 alkyl; and R 15~ R 16 and R 17 are independently hydrogen or Ci -6 alkyl;
or a pharmaceutically acceptable salt or solvate thereof.

Alkyl groups, whether alone or as part of another group, can be straight chained or 1s branched. Compounds of formula (I) are capable of existing in stereoisomeric forms incl.udi.r.g enantiomers and the invention extends to each c'r these stereoisomeric forms and to mixtures thereof :r:ciudirlg racr;inates. The inventio;1 nlso extends to any tautorneric for*ris and mixtures tliereoi.

Preferably the compound of formula (I) has the fo'!owing ste.recchemistr?r-NiN
/
N~~ N H R (~~~ ~, ~,.= ,~ ~/
~......_. ~ ~ '~.
/N
R 4' 3 R ~ .
SRt (Ia) Suitably R" is a C 1-6 alkyl, C2-6 alkenyl, C2-6 alkenyl, C3-8-cycloalkyl or a phenyl group, each group being optiowallv substituted h; one or ir.o:'e substituents selected from halogen, OR'~, Nfz.9R10, SR '1 or Ci.,6 alkyl (icself optiorially substituted by one or more halogen atoms). Preferably R is C 1-4 alkyl or phenyl each of w{iich can be substituted by trifluoromethyl. More pre-'erably R' is propyl, butyl, trifluoromethylphenyl or 3,3,3,-trifluoropropyl.

Suitably R2 is C1-g alkyl optionally substituted by one or more substituents selected from halogen, OR 8, NR9R10, SR1;, C3-8-cycloalkyl, aryl (optionally substituted by one or more alkyl groups and/or halogen atoms), or C 1-6-alkyl; or R2 is a C3-8-cycloalkyl group optionally substituted by one or more substituents selected from halogen, ORg, NR9R10~
SR11, C1.u-alkyhor phenyl, the latter two groups being optionally substiatted by one or more substituents selected from halogen, NOZ, C(O)Rg, OR8, SR11, NR12R13, a fused 5-or 6-membered saturated ring containing one or two oxygen atoms, phenyl or C1-6-alkyl the latter two groups being optionally substituted by ORg. NR9R10 or one or more halogeri ato*r:s. ~,ryl groups include phenyl and naphthyl groups. Acyl groups io include C(O)C1 .6 alkyl such as acetyl and 1-oxopr.opyl. Preferably R' is C1-6 alkyl or a C3-8-cycloalkyl group optionally substituted by phenyl. More preferably 1~ is butyl or cyclopropyl optionally substituted by phenyl, the phenyl group itself being optionally substituted by one or more halogen, C3-g alkyl, alkoxy, phenoxy or pheny., groups.

Suitably one of R3 and R4 is hydroxy and the other is hydrogen, hydroxy or '2 41 Preferably R and 2' are both hydroxy.

Suitably R is a group (CR/R6 )mOR7 where m is 0 or 1, R' and R5 are independently hydrogen, C1-6 alicyi or phenyl the latter two groups being optienally substituted by halogen, and R7 is hydrogen, C1-6 aikyl or (CR'R6 )õRi44uhere R'' and R6 are as defined above, n is 1 to 3 and R14 is COOH, OR1 NR1vR1~~ or CUNR1eR'. ; or R is a C1-4alkyl or C2-4 alkenyl group, each of which is substituted by oae or i..ore groups selected from =S, =O,. =ti'R20 or 0 _2i P~ac7. optionally substituted oy one or more groups selected from halogen, C 1-4 aik,~~;, pl-ieny i, SR21, i~1"OZ or NR22R?3 (wh~-. e R21, R22 and R2 3 are indPpend ntly hydrof;en, Ci_4 all:yl or nhenyl; R20 is rJk?4 or.r NR25R26 where R24 is hyc~.rogen, ~C1-4 a'.'cy,. or nhFnyl, and R s and R26 are inder,enclently b,y(Irogen, Cl.-4 alkyl, aryl, C1-E acyl, arylsu'iphonyl or arylrarbonyl).

Preferred R groups include OH, CH2OH, CH2CH,)OH, OCH?CH2OH, CH2OCH2C(CH3)jOH and OCH2C(CH3)2OH..

Particularly preferred comnounds of the inventior, include those exemplified herein both as free oases and as pharmaceutically acceptable salts and solvates.

According to the invention there is further provided a process for the preparation of a compound of formula ;I) which comprises:
(a) reacting a compound of formula (II):

N=N
R N

N
-4 N\,/

S SRl (n) where R, R1, R3 and R4 are as defined in formula (I) or are protected derivatives thereof or R3 and R4 together form a bond, and L is a leaving group with a compound of formula (III):
R2NH2 (LI) where R2 is as defined in formula (I) or is a protected derivative thereof, or (b) reacting a compound of formula (IV):

U
N=N
N /NHR Z
rJ2 ~
N N

SR (IV) in which R1 and R2 are as ,: fsfnect ici formula (T) cr are protected dPrivative;s thereof and P~
and P2 are protecting g~oups or hydrogen, with a suitable re .genL ro introduce a substituent R, or, for compounds where m is 0:
(c) hydroxylation of a compound ot formula (V):

N =N

N
SRI (V) where R', R2 and R7 are as defined in formula (i) or are protected derivatives thereof, and optionally thereaft.-.r (a), (b) or (c) and in any order:
= converting one or more functional groups into a further functional groups = removing any protecting groups = forming a pharmaceutically acceptable salt or solvate.

Compounds of formula (II) can be reacted with arnines of formula (III) in the presence of a base. such as a tertiary organic amine in an inert solvent such as dichloromethane at ambient or elevated temperature. Other suitable bases include inorganic bases such as potassium carbonate.

When one or both of R3 and R4 are hydroxy they can be protected as groups OP' and OP2 is where P' and P' are protecting groups. Examples of suitable protecting groups in compounds of formula (II) and (IV) are C1.6 alkyl (preferably methyl), benzyl, (C;.6alkyl)3Si (preferably t-butyldimethylsilyl), and a C(O)Ci.6alkyl group such as acetyl.
When both of R3 and R' are hydroxy preferably the two groups P' and Pz together with the atoms to which they are attached form an alkylidene ring such as a methylidene or isopropylidene nng. .Alternatively P' and PZ can form an alkoxymethylidene ring such as ethoxymethylidene.

Protecting groups can be added and removed using known reaction conditions.
The use of protecting groups is fiilly described in 'Protective Gioups in Organic t'hemistry', edited by J
W F McOmie, Plenum Press (19"?3), and 'Protective Groups in Organic Synthesis', 2nd edition, T W Greerie & P G M Wutz, W iiey-Interscience (1941).

Ester protecting groups can be rernoved by basic hydrolysis, for example by using a metal hydroxide, preferably an alka.li metal hydroxide. surh as sodium hydroxide or lithium hydroxide, or quaternary arrlmonium hydroxide in a solvent, such as aqueous ethanol or aqueous tetrahydrofuran,at a temperature of from 1.0 to 100 C, preferably the temperature is around room temperature; or by acidic hydrolysis using a mineral acid such as HCI or a strong organic acid such as trichloroacetic acid in a solvent such as aqueous 1,4-dioxane.
Trialkylsilyl protecting groups can be removed by the use of, for example, a fluoride ion source, for example tetra-n-butylanunonium fluoride or hydrogen fluoride.

When one or both of P' and Pz are C1-6 alkyl, deprotection can be acheived using boron tribromide.

io Benzyl groups can be removed by hydrogenolysis using a transition rrletal catalyst, for example palladium on charcoal, under an atmosphere of hydrogen, at a pressure of from 1 to 5 bar, in a soivent, such as acetic acid.

A compound of formula (II) can be prepared by diazotising a compound of formula (VI):

R" ~,-N, L
_._... 1 1 N IN
4 ~ i~3 F~

SR1 ('~I) wherein R and R' are as defined in formula (I) and l- is as defir..ed above and R3 and R4 are as defined in formula (I) c r are protected derivatives thereof or R3 and R4 together form a bond, with a metal nitrite, for example an alkali metal nit;-ite, especially sodium nitrite in dilute aqueous acid, for example 2M HCl, or wich a CI -h-.alrcyl nitrite in an inert solvent, at a temperature of from -20 tc) 100 C; preferred conditions are isoamyl nitrite in acetonitrile at 80 C.

A Compound of formula (VI) wherein R is CH2OH, and R3 and R4 are hydroxyl or protected derivatives thereof, L is as defined above, can be prepared by reducing a compound of formul.a (VIl):

I L
+
O~ ~N
O' N N SR
OPl OP2 (VII) wherein R1, L, Pl and P'' are as defined above. The reduction of the nitro group can be carried out for example b.I using hydrogenation with a transition metal catalyst at a temperature around room temperature, for example paliadi~i-al on charco?l under an atmosphere of hydrogen, preferably at a pressure from 1 to 5 atmospheres, in a solvent, for example ethanol, or by using iron in an acidic solvent such as acetic acid at a temperature of about 100 C.

io Reduction of the lactam can be carried out using cumplex metal hydrides such as lithium aluminium hydride in a soivent sucn as ether or preferaaly by using sodium borohydride in a suitable solvent sucri as niethaiiol.

A compound of formula (VTI) can be prepared by reacting a compound of formula (VIII):

I+
O~
L N SR
(vra) wherein L and R1 are as defined above and Lt is a leaving group, for example a halogen atom, wherein L and Ll are preferably the same, with a compound of formula (IX):

O H
N
P0 OP2 (IX) wherein P1 and P 2 are as defined above, in the preserce of a base such as C1_6-alkyl-M or MH wherein M is a metal ion, for example n-butyl lithium, in an inert solvent, such as s tetrahydrofuran (THF), at a temperature of from -10 to lOOC. Preferably sodium hydride is used in THF at room temperature. Preferably the compound of formula (IX) has the following stereochemistry such that the above reactions give a compound of formula (Ia):

O H
N
I' 1C OP' (IXa) io One or more functional groups can be converted into further functional groups using standard chemistry. For example a compound where ?t' is hydrogen can be converted to a compound where R7 is CH2COOH by 'Lreating with a compound of formula (X):

15 R18OC'OCt1.=Nz (X) where R18 is C1-6 alkyl in the presence of.rhodium acetate, followed by hydrolysis of the resulting ester. A compound where R7 is hydrogen can be converted to a compound where R' is (CHZ)õRi4 by treatment with base followed by L(CHZ),,R'' where L is a leaving group 20 and R14 is as defined above or a protected version thereor. The group SR' can oe interconverted by oxidation of the sulfur, for example usir,g oxoneTM or MCBPA, followed by treatment with a compound R"-SM where R" is a different R' group and M is a metal such as sodium.

25 Compounds of formula (IV) can be reacted with a suirable reagent to intioduce the R group using conventional chemistry. F'or exampie compounds of formula (IV) can be reacted with ZnJH2S04 to give a compound of formula (I) miere R is COCH?OH; with HI to give a compound of formula (I) where R is COCH3; or vnth BF3/R'OE1 (e.g- methanol) to give a compound of formula (I) where R is COCH20R', or with light followed by a reducing agent (eg DIBAL-H) to give a compound of formula (I) where R is Cl-LCH2OH.
Compounds of formula (IV) can be prepared from compounds of formula (XI):

N =N

HO N ~
~ I .
~ lv r~
oP' oP2 Y, SR' (XI) in which R', R2, Pl and P2 are as defined abovo by treatment with an activating agent, such as an acyl chloride, followed by diazomethane. Compounds of formula (XI) can be 10 prepared from compounds of formula (VII) as defined above by reduction of the nitro group followed by hydrolysis. Hydrolysis can be perforrned using a mineral acid such as HCl or a strong organic acid suw!: as trifluoroacetic acid. Preferably the reduction and hydrolysis are carried out simultaneously using iron in an alcoholic solvent, for example ethanol, containing an alkaline earth halide such as calcium chloridE: at a temperature of about 80"C.

Compounds of formula (VI) can also be prepared by treating a compound of formula (XII) !-i ~__...~
~<-R R (XII) where R3 and R4 are as defined in. formula (I) or are protected derivatives thereof or R3 and R4 together form a bond with a compound of formula (VLTI) as defined above, followed by reduction of the nitro group. Th(- reaction is carried out in an inert so)vent such as dichloromethane or 1,4-diox.ane in xi e presen:.e of a rion-nucl:~nphilic base such as N,N-diisopropylamine at a temperature of a bout -2.0 C to about 150 C, preferably at ambient temperature.

Preferably the compound of formula (XII) has the following stereochemistry such that the above reactions give a compound of formula (Ia) as defined above R rNH2 R R (XIIa) Compourids cf formula (~17) where R' ar_d R4 ibir.: a bor:d Lnci L:s SR' can be prepared by reacting a compound of formula (XIII):

i,'~=N
HNl SR
il N ~ N

SR (XIII) in which R' groups are as defined L-, iorw.ula (I) with a compound of formula (XIV):
R'O~-. ,,,,OAc (XIV) in which R5 is as defined in formula (I). The reaction can be carried out in the presence of a suitable transiti.rn metal :oAn.p.'.:.h pr:rc-,arlv :etrakistriph~~,yl. ~' .asp::,:ne palladium (0).
Compounds of formula (XIII) caz be prepared from compounds of formula (XV):

SH

H2N'' N SH ~~,~,~

by reacting with a compound R'X where R' is as defined in formula (I) and X is a leaving group such as halo, followed by cyclisation.

The amines R2NH2 can be prepared using procedures described in H Nishiyama etal, Bull.
s Chem. Soc., JpnA 1995, 68, 1247, P. Newman, Optical Resolution Procedures for Chemical Compounds, Vol. 1, Amines and Related Compounds; Optical Resolution and Information Centre: Manhattan College, Riverdale, NY, 1978, p12Q, J.
Vallgardaetal, J.
Chem. Soc. Perkin 1, 1994, 461. Certain amines RZNH2 are novel compounds and form a further aspect of the invention.
to All novel intermediates form a further aspect of the invention.

Salts of the compounds of formula (I) may be formed by reacting the free acid, or a salt thereof, or the free base, or a salt or a derivative thereof, with one or more equivalents of as the appropriate base (for example am.-nonium hydroxide optionally substituted by C1-6-alkyl or an alkali metal or alkaline earth metal hydroxide) or acid (for example a hydrohalic (especially HCl ), sulphuric, oxalic or phosphoric acid). The reaction may be carried out in a solvent or medium in which the salt is insoluble or in a solvent in which the salt is soluble, e.g. water, ethanol, THF' or diethyl ether, which may be removed in vacuo, 20 or by freeze drying. The reaction may also be a metathetical process or it may be carried out on an ion exchange resin. The non-toxic physiologically acceptable salts are preferred, although other salts may be useful, e.g. ir.. isolating or purifying the product.

The compounds of the invention act as P2T receptor antagonists. Accordingly, the 25 compounds are useful in therapy, especially adjunctive therapy, particularly they are indicated for use as: inhibitors of platelet activation, aggregation and degranulation, promoters of platelet disaggregation, anti-thrombotic agents or in tiie treatment or prophylaxis of unsr.able angina, coronary angioplasty (PTCA), myocardial infarction, perithrombolysis, priznary arterial thrombotic complications of atherosclerosis such as 30 thrombotic or embolic stroke, tr.msient ischaemic attacks, peri.pheral vascula_r disease, myocardial infarction with or without thrombolysis, arterial complications due to interventions in atherosclerDtic disease such as angioplasty, endarterectomy, stent placement, coronary and other vascular graft surgery, thromtiotic complications of surgical or mechanical damage such as tissue salvage following accidental or surgical trauma, 35 reconstructive surgerr including skin and muscle flaps, conditions with a diffuse thrombotic/platelet consuniptior, component su(:h as disseminated intravascular *rB

WO 99/05143 PCT/SE98/,01393 coagulation, thrombotic thrombocytopaenic purpura, haemolytic uraemic syndrome, thrombotic complications of septicaemia, adult respiratory distress syndrome, anti-phospholipid syndrome, heparin-induced thrombocytopaenia and pre-eclampsia/eclampsia, or venous thrombosis such as deep vein thrombosis, venoocclusive disease, haematological conditions such. as myeloproliferative disease, including thrombocythaemia, sickle cell disease; or in the prevention of mechanically-induced platelet activation in vivo, such as cardio-pulmonary bypass and extracorporeal membrane oxygenation (prevention of microthromboembolism), mechanically-induced platelet activation in vitro, such as use in the preservation of blood products, e.g. platelet concentrates, or shunt occlusion such as in {o renal dialysis and plasmapheresis, thrombosis secondary to vascular damage/inflammation such as vasculitis, arteritis, glomeruionephritis, inflammatory bowel disease and organ graft rejection, conditions such as migraine, Raynaud's phenomenon, conditions in which platelets can contribute to the underlying inflammatory disease process in tne vascular wall such as atheromatous plaque formatiorvprogression, stenosis/restenosis and in other inflammatory conditions such as asthrria, in which platelets and platelet-derived factors are implicated in the inununological disease process.

According to the invention there is further provided the use of a compound according to the invention in the manufacture of a medicament for the treatment of the above disorders. In particular the compounds of the invention are useful for treating myocardial infarction, thrombotic stroke, transient ischaemic attacks, peripheral vascular disease and angina, especially unstable angina. The invention also provides a method of treatment of the above disorders which comprises administering to a patient suffer.ng from such a disorder a therapeutically effective amount of acorr..pound according; to t:-le ?nvent.ion.
The compounds may be adrnznistereti topically, e,g. to the lung and/or the airways, in the form of solutions, suspensions, !FiFA aerosolr, and dry powjer formu:ations;
or systemically, e.g. by oral administration in the form of tabiets, pii1s, capsul, s, syrups, powders or granules, or by parente,:al ad!xtinistration in th: 4orm of sterile parenteral solutions or suspensions, by subcutaneous admimstration, or b}, rectal administration in the form of suppositories or t.ransdennali.y.

The compounds of the invention may be adininistered on their own or as a pharmaceutical composition comprising the compound of the invention in combination with a pharmaceutically acceptablf, diluent, ad~,uvant or carrier. Particularly preferr=ea are composit;.otis not containin; materia~l capable of causing ari aCver.se, e.g.
an allergic, reaction.

Dry powder formulations and pressurised HFA aerosols of'tile conipounds of the invention may be administered by oral or nasal inhalation. For inhalation the compound is desirably finely Jivided. The compounds of the invention may also be administerPd. by means of a dry powder inhaler. The inhaler may be a sing!e or a mul:.i dose inhaler, and may be a breath actuated dry powder inhaler.

One possibility is to mix the frn-Ily divided cornpound with a ca:Tier substance, e.g. a to mono-, di- or polysaccharide, a su;ar alcohol or another polyol. Suitable carriers include sugars and starch. A.lternative:y cne r'inely divided compoucxi may "oe coai:ed by another substance. The powder mixture may also be dispensed into hard gelatine capsules, each containing the desired dose of the active compound.

Another possibility is to process the finely divided powder into spheres which break up 5 during the inhal4tion procedure. This spheronized powder may be filled into the drug reservoir of a multidose inhaler, e.g. that known as the Turbuhaler in which a dosing unit meters the desired dose which is then inhaled by the patient. With this system the active compound with or without a carrier substance is delivered to the patient.

10 The phannaceutical composition comprising the compound of the invention may conveniently be tablets, pills, capsules, syrups, powders or graAules for oral administration;
sterile parenteral or subcutaneous solutions, suspensions for parenteral administration or suppositories for rectal administration.

15 For oral administration the active compound may be admixed with an adjuvant or a carrier, e.g. lactose, saccharose, sorbitol, mannitol, starches such as potato starch, corn starch or amylopectin, cellulose derivatives, a binder such as gelatine or polyvinylpyrrolidone, and a lubricant such as magnesium stearate, calcium stearate, polyethylene glycol, waxes, paraffin, and the like, and tnen compressed into tablets. If coated tabiets are required, the 2o cores, prepared as described above, may be coated with a concentrated sugar solution which may contain e.g. gum arabic, gelatine, talcum, titanium dioxide, and the like.
Alternatively, the tablet may be coated with a suitable polymer dissolved either in a readily volatile organic solvent or an aqueous solvent.

For the preparation of soft gelatine capsules, the compour.d may be admixed with e.g. a vegetable oil or polyethylene glycol.lH:ard gelatine capsules may contain granules of the compound using either the above mentioned excipients for tabler7, e.g.
lactose, saccharose, sorbitol , mannitol, starches, cellulose derivatives or gelatine. Also liquir or semisolid formulations of the drug may be rilled into hard gelatine capsules.
Liquid preparations for oral application may be in the form of sllnips or suspensions, for example solutions containing the compound, the balance being s yar and a m,ixture of ethanol, water, giycerol and propyletie glycol. Optionally such licauid preparations may contain colouring agents, flavouring agents, saccharine aiid :art,Dxyrnethylcellulose as a thickenitig agent or other excipients l~.r~own to those skilled in art 15a The invention also provides a commercial package comprising a compound or composition of the invention and associated therewith instructions for the use thereof in the treatment or prevention of the above disorders.

The invention is illustrated by the following examples. In the examples the NMR spectra were measured on a Varian Unity Inova 300 or 400 spectrometei- and the MS
spectra were measured as follows: El spectra were obtained on a VG 70-250S or Finnigan Mat Incos-XL
spectroineter, FAB spectra were obtained on a VG70-250SEQ spectrometer, ESI
and s APCI spectra were obtained on Finnigan Mat SSQ7000 or a Micromass platform spectrometer. Preparative HPLC separations were generally performed using a Novapak , Bondapak or Hypersil column packed with BDSC-18 reverse phase silica. Flash chromatography (indicated in the Examples as (Si02)) was carried out using Fisher Matrix silica, 35-70 m. For examples which showed the presence of rotamers in !he nroton NMR
spectra only the chem:zal shifts of the r.naior rotamer are quote.d.

For compounds prepared bx- par.3llel synthesis the products were taken ir.to ethanol (500g1) and analysed using an analytical HPLC machine (HP1100), against a standard calibration curve, in order to estimate the concentration of the product. The ethanol was evaporated 1s and the residue taken into an appropriate volume of DMSO, based on the HPLC
analysis, to yield a solution of 'naNI concencrat:o,i ror biological tcsting.

Example 1 [iS-[1 a,2a,3(3,5[i(1S*,2R*)]]-3-(Hydroxymethyl)-5-[7-[(2-phenylcyciopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yl]-cyclopentane-l,2-diol a) [3aR-[3aa,4a,6oc(1R*,2S*),6aot]-Tetrahy dro-2,2-dimethyl-6-[7-[(2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yl]-4H-cyclopenta-l,3-dioxole-4-methanol N,IV=Diisopropylethylamine (21nz1) was added to a solution of [3aR-(3a(x,4a,6oc,6aa)]-6-[7-chloro-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrinudin-3-yi j-tetrahydro-2,2-dimethyl-4H-cyclopenta-l,3-dioxole-4-methanol (prepare(i as described ia W U 9703084) (55g) and (1R-trans)-2-phenyl-cyclopropanamine, [R-(R*,R*)1-2,3-dihydroxybutanedioa~e (1:1) (prepared as described by L.A. iVlitscneret al., J. Med. Chem. 1986, 29, 2044) (11.3g) in is dicnloromethane (500ml). '1'he reaction mixture was stirred at room temperature for 3 hours, then washed with water, driea and evaporated. The residue was purified (Si02, ethyl acetate:dichloromethane 3:7 as eluant) to afford the subtitle compound (19g).
MS (APCI) 497 (M+NT, 100%) b)[1S-[l0c,2a,3(i,5(3(1S*,2R*)]]-3-(Hydroxymethyl)-5-[7-[(2-phenylcyclop .ropyl)arninoJ-5-(propylthio)-3.H=1,2,3-triazolo [4,5-d}' pyrimidin-3-yl]-cyclopentane-l,2-diol A solution of the product from step (a) (18.5g) in methanol ( l L) and 2N HCl (150m1) was stirred at room temperature for 2 hours and concentrated in vacuo. Water (500m1) was added and the product was collected by filtration and dried (16. ; g) MS
(APCI) 457 (i%2+2i+, iGO~'~o) NMR El-I (d6-DMSO) 9.33 ('_H, d), 7.30=-7.16 (5H, m), 5.01 (2H, rr;, 4.72 (2I-', m), 4.43 (1H, m), 3.87 (1H, d), 3.48 (2K, m), 3.20 (1H, m), 2.95 and 2.85 (2H, 2x m), 1-26 (1H, m), 2.12 (2H, ra), lri, m;, 1.4c) (314, cn.), 1.33 (111-I, m), t).

Example 2 [ 1R-(1 a,2(x,3 (3,5 p)J-3-[7-[(Cyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol a)[3aR-(3aa,4oc,6a,6a(x)J-6-[7-[(Cyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo [4,5-dJ pyrimidin-3-yl]-tetrahyd ro-2,2-dimethyl-4H-cyclopenta-1,3-dioxole-4-methanol A solution of [3aR-(3aa,4a,6a,6a(x)]-6-[7-chloro-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyriniidin-3-yl]-tetrahvdro-2,2-dimethyl-4H-cyclopenta-1,3-dioxole-4-methanol (0.5g) and cyclopropanamine (0.3m1) in 1,4-dioxane (20m1) was heated to reflux. The heat source was removed and the reaction mixture was stirred for 1 hour. r he mixture was concentrated and the residue purified (Si02, ethyl acetate: isohe,:ane 1:1 as eluant) to afford the subtitie compound (0.4g).
MS (APCI) 421 (h/i+H', 100%) b) [1R-(loc,2a,3(3,5[3)J-3-[7-[(Cyclopropyl)aminoj-5-(propyithio)-3H-1,2,3-triazolo[4,5-ct'Jpyrimi(.lin-.3-yi]-5-(hydroa ,rynr.ethyl)-cyclol*entane-:i,2-diol A so:uLcn of the prodLLct frc~.n step (a.) (0. 12g) in tAfluonoat!eL:.c acid.
(4rnl)/water (lml) was stirred at room temperature f-,r. 2 hours, poured into dilnt-- a-queous sodium bicarbonate and extracted with d.ich'.c,rcYnethane. ; he extract was coricentrate ;. and purified (Si02, ethyl acetate as eluant;, to :,fford 'the titie corripound (0.lOg).
MS (APCI) 381 (M+H+, 100%) NMR S'-: (d6-DMSO) 9.00 (1H, s), 5.00 (2H, m), 4.70 (2H, rn). 4.45-4.40 (11I, m), 3.90 (1H, br s), 3.50-3.40 ,2E, rr:), 31C-3.00 (:SH, m), 2.25-2.20 (ily, i.i), 2.19-2.16 (1H, m), 1.90-i.80 (1H, m), i.80-1.60 (2H, m), i.00 (31f, t), 0.90-0.60 (4H, m).

ExampYe 3 [1R-(1 a,2oc,3(3,5(3)J-3-[7-(}3utylamino)-5-(propylthio)-3H-1,2.3-triazolo [4,5-d] pyrsrz 9,Jin-3-y1;-5-(?hydroxymethyl)-cyclopentane-1,2-diol The tit!e co-r_pouncd, vir:> pr-;pared -:r,)rn [3:iFC-(3aa.4tx,6~c,~af~c'y? 5 f?(bLl*.ylar:lin.o)-5-(prop:,~itlxi~l) 31~ :,',? c:~i;iz,i:,'oi'~>5 c/jP'r=?::,id:n 3 y1J _:.,rur!
!;irr ~:,~ clirri: thyi-4FI-cyclopcnta-1,3-dioxoie-4-rriethanoi (prepared as described in 'h'O 9703094) according to the rnet;lod of example 2 step (b).
MS (FHI3) 391 ("4=+-i-iF., i00 r o) NMR SH (d6-DMSO) 6.25 (1H, m), 5.15 (1H, s), 5.00 (1H, m), 4.45 (1H, m), 4.25 (1H, s), 3.90-3.60 (4H, m), 3.10 (2H, m), 2.94 (1 H, s), 2.75 (1H, m), 2.45 (111, m), 2.20 (1 H, m) 2.05 (1H, m), 1.78 (2H, m), 1.65 (2H, m), 1.46 (2H, m), 1.07 (3H, t), 1.00 (3H, t).

Example 4 [1R-(la,2a,3(3,5(3)]-3-[7-(Butylamino)-5-[ [4--(trifluoromethyl)phenyl]thio]-35-1,2,3-triazolo [4,5-d] pyrimidin-;3-ylJ-5-(hydroxymethyl)-cyclopentane-l,2-diol a)[3aR-(3aa,4(x,6a,6aa)[-5-[7-(Butylamino)-5-(proplilsulfonyl)-3;,->1,2,3.-triazolo[4,5-lo dJpyrir,.iidin-3-yll-*etrahydro-?,2-dimethyl-4H eyclopenta-l,:3-dioxole.-4-rn.ethanol 3-Chloroperoxybenzoic acid (1.0g) was added to a solution of [3aR-(' )aa,4(c,6ce,6aa)]-6-[7-(rtitvlaruno)-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxole-4-methanol (0.88g) in dichloromethane (IOOml) and the resulting solution was stirred at room temperature for 18 hours. The solution was washed with aqueous sodiurri rnetabisulfite solution (3 x tOml) then dried and concentrated. Purification (Si02, ethyl acetate as eluant) afforded the subtitle compound (0.3g).
MS (Alji:i) 469 (14+11{, 100%) b)[L,,1?-? ' 3aa,4a,6a,6aa)]-6-[7-(Butylamino)-5-[[4-(trifluoromethyl)ph:enyljthio]-3H-1,2,3=triazoio [4,'.>-eJ pyrirn idir..-3 .,y i j-tet, arilZ 41 -o..'i,2 -flimetiiyi-417-cy(:i open ta-1,3-dioxole-4-rnethanoy 4-(T'ritiuoromethyl)thiophenol (0.18g) was added to a suspension of sodium hydride (60%, 40mg) in 'THF (10m1). After 30 rninutes a solution of the product of step (a) (0.23g) in THF
2s ( lOrnl) was added dropwise and the reaction stirred for 45 minutes. The reaction mixture was added slowly to a solution of sodium. chloride (lOzr.l.) cor.taining aceti.c acid (1ml) then the solution extra.ted with thvl acetate (50m1).. The organic phase wv, dried and conceztrated and the residue purified (Si02, diethyl ether to riieth.yl ether:ethar..ol 9:1 as eluant) to give the suotitle compouna.
MS (AR'CI) 539 (iVI-F-Hr",lO0%;) c) [1R-(la,2or.õ3[i,5(3))-3-'7-(Butylamino)-5-[[4-(7t.rifluoi-omethyl)phenyl]thio]-3H-1,2,3-triazolo k4,5-d.1lsyrimidin-3-yi ]-5-(hydrox3,methv))-vyclopente.n+e-?,?-Ainl Prepared accordi.r.g, to the method of examale 2, s'ep (h). F-i.sinci the the product of step (b).
MS .469 (1~~ ~ rx ,1 aO%) NMR SH (d6-DMSO) 9.08 (IH, m), 7.88-7.78 (4H, dd), 5.00-4.91 (2H, m), 4.71-4.64 (2H, m), 4.36-4.30 (1H, m), 3.80-3.75 (1H, m), 3.42-3.17 (1H, m), 3.29-3.15 (211, m), 2.52-2.08 (3H,. m), 1.80-1.70 (1H, m), 1.37-1.32 (2H, m), 1.17-1.07 (2H, m), 0.77 (3H, t).

5 Exarr.ple 5 2-[[ [1R-(1 a,2 j3,3 p,4(x)]-4-[7-(Butylamino)-5.=(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-ylj-2,3-dihydroxy-cyclopentyljmethoxyjacetic acid a) [3aR-(3aa,4a,6a,6a(x)j-2-[6-[7-(F3utylamino)-5-(propylthio)-3hi-1,2,3-triazolo [4,5-1o djpyrimidin-3-ylj-tetrahydro-2,2-dimethyl-4H-cyclopenta-i,3-dioxole-4-methoxyjacetic acid, ethyl ester A solution of [3aR-(3aa,4a,6a,6a(x)]-6-[7-chloro-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyri:niclin-3-yl]-tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxole-4-methunol (0.7g) and rhodium acetate (0.39g) in dicinioromethanc (20rn1) was treated with a solution of ethyl 15 diazoacetate (0.2im1) in aichioromethane (lllnzl) over 3 hours. The reaction mixture was stirred at room te-nperature for 60 hours, concentrated and pur .fied (SiO2, isohexane:ethyl acetate 3:1 as elttant). 'f he resulting intermediate was taken into 1,4-di.oxane (lOml), n-butylamine (0.2m:) added and the solution stirred for 18 hours then ccncentrated.
Purification (Si02, dichloromethane to dichloromethane:ethyl acetate 8:2 as eluant) gave 20 the subtitle compound (0.2g).
MS (FAJ3) 523 (M+H', 100%) b) 2-[[[1R-(1a,2(i,3p,4a)j-4-[7-(Butylamino)-5-(propylthio)-3H 1,2,3-triazolo[4,5-djp3 rirnudin-3-y1;-2,3-dili,ydroxy-eticloFentliljinetlaoxylacetic acid, ettiyl ester Prepared according to thP method of example 2, step b) using tiic proc:uc.t of step a).
MS (FAB) 483 (1V1+1=i:' , l00io) d) 2-,l; '..~?-(1a,2~i,~3[3,4(~c)j-4-[7-(Butylamino)-5-(nropylthio)-3,H-1,2,3-=trir!7olo[4,5-d] pyy iniiclin-:l-yl1=.ci -cwlopent,ykjmethc. ryjacet.ic acid A mixture 41-Fthe , n cduc,, ~c~rri step <<:) (46mg) 4nd :ithiuni hy,.jro-adcj monohydrate (8.5mg) in tetrahydrofuran (lfilxil) was stirred for 18 hours theri concentrated. Plz, ification (SiO2, dichloroinetnane !.o etY:yi acetate to et.hv.i acetate:metr:;ar.c: rnuiion;
afforded the title compounci (0.04p MS (FA>=3) 45:i (ri1+i1+,10d%) NMR 8H (d6-DMSO) 12.00 (1H, m), 8.97 (1H, m), 4.99 (2H, in), 4.82 (1H, ni), 4.42 (2H, m), 4.64,,21F1, m), :3.:1'~ ('211, iri), 3.60-3.51 (1H, m), 3.50-3.40 (31-1, m), 3.10-3.00 (2H, t), 2.30-2.20 (2H, m), 1.88 (1:~H, m), 1.67 (2H, m), 1.55 (4H, m), 1.33 (2H, m), 1.07-0.83 (6H, m).

Example 6 1-[(1S-'1 o~,2p,3(3,4a(1S*,2R*)]]-2,3-Dihydroxy-4-[7-[(2-phenylcyclop~-0p) I)amino]-5-(propylthio)-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yl]-cyclopentyl]-2-hydroxy-ethanone a) [3aR-(3aa,4a,6(x,6aa)J-6-[[5-Amino-6-chloro-2-(propyithio)-4-pyrimidinyl]amino]-tetrahydlro-2,2-dlimethyl-4H-cyclopenta-1,3-dioxole-4-carboxylic acid io Iron powder (10.0g) was added to a stirred solution of [3aS-(3a(x,4j3,7[3,7aa))-5-[6-chloro-5-nitrc-2-(propylthio)-pyrimidin-4-yl]-tetra.hydro-4,7-methano-2,2-dimethyl-1,3-dioXoio[4,5-c]pyridin-6(3aH)-or.e (prepared as described in wv 9703Cb4) (iv.Og), and calciam chloride in echarcoi (14Gmi). 7ne reaction m.ixture was neatecl ai reflux for 10 minutes then filtered through celite, washing several times with hot ethanol.
The filtrate was concentrated co ar'fioYc, the subtizie compound (9.3t;).
MS (F'A13) 405, 403 (Ivf+H+), 405 (1006io).

b) [3aR-(3aa,4a,6(x,6aoc)]-6-[7-Chloro-5-(propylthio)-3H-1,2,3-triazolo[4,5-2o d]pyrimidin-3-yl]-tetrahydro-2,2-dimethyl-4H-cyclopenta-1.3==dioxole-4-clrboxylic acid Isoamyl nitrite (6.02m1) was added to a solution of the product of step a) (9.28g) in acetoni*xile (80m1) and the soltition heated at 70 C: for 1 hour.e 1he cooied reaction mixture was cot.centrateci antt I-urif:: d(SiG~, ethvl acetate:isoiiexarie u:1 as eluar-t) to afford the subtitle compound (7.9g).
MS (FAB) 416, 4.14 (M+:H+), 414 (1.00%).

c) [:!aR-(3aa,4a,E-tx,baa)] ''etralrycir~l-x,'l-alimethy4-(,.;'1 [(?
pihenylcyclopropyl)am:'<ac] 5-(ls;~opy'thio)-3.?~I-1.;2,3-triar~,ln,<<,.~-~jp,vrirrl4cfin-3-yl]-4H-cyciopenta-1,3-dioxol.z-4-carhoxylic acia Prepared accordiag to ':1t r,.athod siiaxample 1, step a) usiaa the prorlu,>e of step b).
MS 511 ;M,-ti' ,: i 1;~Io), d) 1-[[1S-[Ia,2(i,3(3;4a(1S':,2R*;)j-2.3-;i)ihydroav-4-[7-'Ii2-l;henylcvclopropyl)amino]-3s 5-(propyltbio)-3H-1,2,?-triazoAo[4,5==al)p}-rimidin-3-yl)-cy:.lopent;rl]-2-lhydroxy-,Ahianone Isobutylchloroformate (0.38m1) was added to an ice-=cooled solution of the product of step c) (0.50g) and N-methylmorpholine (0.11 ml) in tetrahydrofuran (20 ml). The solution was then stirred at room tempecature for 90 minutes before adding to a solution of diazomethane (1.0g) in ether (100m1). The solution was stirred for 30 minutes then cor,centrated and=the diazoketone purified (Si02, isohexane :diethylether ?.:'. ?s ~!luant). The diazoketone (0.25g) was taken into 1,4-dioxane (10 ml) / 2N sulphuric acid (10 ml) then heated at 40 C for 2 hours. The reaction mixture was extracted into ethyl acetate and the extracts washed with water then dried and concentrated. Purificw:ion (Hf'LC, Novapak C18 column, 0. i~io aqueous ammonium acetate:aceconitri ie, gradient elutior.
'70:30 to 0:100 io over 15 minutes) afforded the title compound (0.09g).
MS (APCI) 485 (1vI+'tir, i00%) NIviR SH (d6-DMSO) 9.36 (llti(, d),'7.31-7.15 (5H, m), 5.24 (2H, t), 5.13 (IH, t), 5.01 (1H, m), 4.33 (1H, m), 4.23 (:?H, m), 4.13 (1 H, m), 3.18 (2I-i, m), 2.96-2.94 ( iI-i, rn), 2.96 -2.84 (1H, m), 2.30 (2H, m), 2.13(1H, m), 1.49 (3h, m), 1.34 (1H, m), 0.81 (3H, t).
is Example 7 1-[[1S-[1a,2(3,35,4a} j-4-( 7-()3utylatnino)-5-(propylthio)-3,0.-1,2,3-triazola[4,5-d]pyrimidin-3-yI J-2,3-d ihvdroxy-cyclr-pent,yl]-2-hydroxy-ethanomA

20 a) [3aR-(3aa,4a,6(x,6aa)]-=f.i-[7-(Butylamino)-5-(propyltkrio)-3.H=-1i2,3-.*.riazolo[4,5-d] pyrimidin-3-y11 -tetra 1?y flro-2,2-dimethyl-4H-c=yclopenxa-1,3-dioxole-4-carboxylie acid The title compound was prJpared according to the method of Ehample I step a) using the product of examp'e 6, stND b) aiid t;autvlamine.
25 MS (APCI) 41i tM+H+, :.tlIDc,cj.

b) '..-[[1S-[1a,2-0,30,4aJ1-,1.-[7=.(l;r ut-ilam;no)-5-(propy:thio)-3,V-1,2,3-'ariazalo[4,5-djpy rimidin.-3-y i j-2,~ -el:"~3=d~=c~xy-cy ~,lopentyl]-:t-=te;/i.-ro?ry-et.1Z arr~L~e Prcpared according to the method of Example 6, step d) using the produc' of step a).
30 MS (APCI) =425 '\i'+I :', NMR =~Ii (d6-'_'.)11.'.ISO) 91~ (111, IH, t), 5.24 ('Il, t), 5.1Z(1H, t), 5.03 (1H, m), 4.39 (!R, ni), 4.~..i ;ll-S, r:i;, ~.13 (111, r:a), 3.51 (71:{, m), 3.1 j (1H, m), 3.09 (lH, m), 2.30 (2:I, m), 1.73 (111, m), 1.61 ;2H, m), 1.38 (2Ii, rn), 1.09 (3H, t), 0.91 (3H, t).

35 Ea:Ainple 8 *rB

1-[[1S-[1a,20,3p,4a(1S*,2R*)][-2,3-Dihydroxy-4-[7-[(2-phenylcyclopropyl)amino]-(propylthio)-3H-1,2,3-triazolo[4,5-rllpyrimidin-3-yl]-cyclopentyl]-ethanone Isobutylchloroformate (2.54 ml) was added to an ice-cooled solution of the product of Exar.-.mple 6, step c) (2.OOg) and N-methylmorpholine (0.52 ml) in tetrahydrefuran (50 ml).
The solution was stirrpd at room temperature for 90 minutes befcre adding to a solution of diazomethane (4.Og) in ether (200m1). The reaction mixture was then stirred for 30 minutes and concentrated. The crude diazoketone (2.05 g) was dissolved in chloroform (50 ml), 47% aqueous HI (215 rr.l) was added and the soiution srirred at rooi-n temperature io for i:1 minutes defore adding saturated sodium tniosulphate solution (iuv ml). The reaction mixture was extracted with dichloromethane and the extracts washed with water, dried and concentrated. The residue was taken into methanol (300 ml), filtered and the filtratc; cancentrated to 1/4 volume before adding trifiuoroacetic acid :
water ( i:1) (50 ml).
After 2 hours the mixture was conceritrated and the residue purified (SiUz, ethyl is acetate:dichloromvthane 1:3 as eluant, then HYLC, Novapax' CiS coiumn, 0.1%
aqueous ammonium acetate:acetonif:ri.le, ;radient elution 60:40 to 0: IOCI over 15 rninutes) to afford the title compound (0.1) g).
MS (APCI) 469 (M+H', 100%) NMR SH (db-DMSO) 9.35 QH, d), 7.31-7.15 (5H, m), 5.2i (2h, m), 4 99 (II-i, m), 4.27 20 (1H, m), 4.17 (1H, m), 3.2 ! (1H, m), 3.10 (1H, m), 2.95-2.83 (2H, m), 2.35 (2H, m), 2.22 (3H, s), 2.13 (iH, m), 1.50 (3H, m), 1.33 (1H, m), 0.83. (3H, *.).

Example 9 (:8vrtylanMrt:)-5 (Prop:Ylti~io) 3 25 dJpvrimidin-3-ytj-?.,3-cdi1h"aclroxy-cycTopen:"vi].-etharl one The title compound was prepared according to the method of F'xzxnple 8 using the product of ?-:xa3nple 7, step a) MS (APCI) 409 (1V1+1I', 1Gt7fllc) 30 NMR SH (.-iS-DM:SO j 3. 96 (11-L. (), 5.22 (ZH, ::.), 5.00 ;' 1 H, q), 4.2,7 (1,H., m,:, 4.19 (1 H, m), 3.48 (2H, m), 3.13 (:3H, zn), 2.32 (211, ni); 2.23 (3H, s), l..?1 (2H, m), 1.0 (219, m), 0.98 (3H, rr), 0.91 0kx., t).

Example 10 [1S-[1o:,2ec,3 [3,5 (3 (IS 1,2R, )]]-3-(1-Hydroxy-l--methylet:ryl)-5-[7-[(2-phenylcyclopropyl)amino]-5-(p ropylthio)-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yl]-cyclopentane-1,2-diol s Methylmagnesium bromide (3M solution in diethyl ether, 4 ml) was added to a solution of the product of Example 8 (0.15 g) in tetrahydrofuran and the solution stirred at room temperature for 30 minutes before adding ice/water (3 ml), followed by 1N
hydrochloric acia (l. ml). The reaction mixture was extracted into ethyl acetate and the extracts washed io with water, dried and eonctntratea. Purification (Hfii1C, Novapak" Ci8 column, 0.1%
aqueous amnionium acetate:acewniirile, gradient elution 'l0:30 to 0:100 over 15 minutes) gave the title compound (0.13g).
MS (APCI) 485 (M+H+, 100%) NMR oH (d6-DMSO) 9.34 (IH, d), 7.31-7.15 ~5H, m), 4.90 (2H, m), 4.57 (iH, m), 4.35 15 (311, m), 3.93 (1H, rn), 3.22 (1H, m), 2.97-2.51 (21-i, m), 2.07 (31-i, m), 1.95 (1H, s), 1.51 (3H, m), 1.33 (1H, m), 1.31 (3H:, s), 1.1 8 (3H, s), 0.80 (3H, t).

Example 11 j1S-[1 a,2 oc,3 (3,5[i(7 S*,2R*)] ]-3-(2-Hydlroxyethyl)-5-[7-[(2-phenylcyclop ropyl)amino]-20 5-(propylthio)-3H-1,2,3-triaGolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol a) [1R-[1a,2~,.3(3,4oc(1R*,2S*)]]-2,3-Dihydroxy-4-,17-[(2-phenv)cyclopropyl)amino]-5-(propy:lthio)-3H-1,2,3-triazolo[4,5-d']pyrimidin-3-ylj-cyciopentaneacetis acid, ethyl estr: r Isonurylchforofori.uate (2.54 ml) was added to an ice-coolc;d sr,10ion of the F,r ,(auct of Exainple 6, step c) (2 .0(ig) aud N-methylmot pholine (0.52 ml) in tetrahydrofuran (50 ml).
The sod.tiation was stin-ed at room temperature for 90 minutes ttien added to a solution of dia:;L,m;.t.hane (4.0g) ir, ether (200m1). The solution was stir-ed for 30 Yr;iiute:; then coucentrated,. 'I'h-. crude diazoketone (1,50 g) wa:y taken inrJ rr,:.manol ~190 r,:1), cooled in icelwat~-,r and. irradiat.ed with a0T00W r:i+:rcu.ry ;an.p ior iU minazes.
'f'he solution was concentrated and purifivd (HF'LC, Novapak C 18 column, 0.1 7o aqueous amrrionium acetate: ace.tonitrile, gradien-c elution 40:60 to 0:100 over 15 rrunutes) to afford the subtitle com*3ound (1).39; =).
MS (APC7) 53) (I-V-C, 100110)).

b) [iS-[la,2a,3(3,5p('tS*,2,R*)]]-3-(2-Hydroxyethyl)-5-[7-[(2-phenylcyclopropyl)amino]-5--(propylthio)-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yl]-cyclopentane-l,2-diol DIBAL-H (1.5 M solution in toluene, 2 ml) was added to an ice-cooled solution of the s product of step aj (0.35 g) in toluene (20 ml) and the solution stirred at *h.is tPmperature for 30 minutes before adding ethyl acetate (2 ml). The solution was concentrated and the residue was taken into trifluoroacetic acid (15 ml) /water (15 nil) and stirred for 30 minutes. The reaction mixture was concentrated and the residue taken into methanol (10 ml) and 1W% aqueous potassiu;il carnonate solutiori (5 ml) added. After 30 minutes the 10 reaction mixture was extracted with etnyl acetate and wasned with water, dried and concentrated. Puriiication (HPLC, Novapak C 18 column, 0.1 % aqueous ammonium acetate:acetonitrile, gradient elution 60:40 to 0:100 over 15 minutes) afforded the title compound (0.21g).
MS (APCI) 471 (M+H', 100%) 15 NMR SH (d6-DMSO) 9.33 ( i H, d), '7.31=1.15 (5H, m), 5.00 (1H, d), 4.96 ( I
H, m), 4.77 (1H, d), 4.5? f 1N:, -), 4.39 (1H, m), 3.7%"- (1H, zn), 3.45 (2I-1, m;, 3.18 (IH, m), 2.87 (2H, m), 2.37 ( l H, m), 2.13 ;1 H. m), 2.03 (1 H, m), 1.75 (2H, m). 1.5 i(4.~i m;' 1.34 (1 H, m), 0.83 (3H, t).

20 Exampie 12 [1S-[1a,2p,3 j3,4oc(1S*,2.R*)]]-4-[7-f (2-Phenylcyclo-arop,yl)amino]-5-(propylthio)-3H-1,2,3-triazol.o [4,5-dl1-yrimidi n-3-yl]-cvclop enta r.-e-1,2,3-triol a) (1:~-~rs) ~-[[6-r":lr;fera-S-nPtr~j-~-{propyitli:o)-pyx-imictin-4--yl]amino]=-7-cvclopentene-25 1-ol To a solutioz of ~,6-dichloro-5==nitro-2-propylthiopy.rimidine (prepared as described in WO
9703084) (4.00g', and trietllylatnine (2.00ml) in dry tes:rahydrofuran.
(=T11r) (100m1) was added a solution of [1S-cis]-4-arnino-2-cyclopenten-l-ol (prcpared as d(scribed by S. F.
Martin et al., Tetrahedror.. :.F;tt., 1992, 33, 358:3) (1.48g) in i'ti1= i 1,4-dioxane 2:1 (150m1) dropw'sF: over 1 houi. The reaction rnixture was filtered, :vncentrateca arid purified (Si02, ethyl acetate:isohexar.e ::4 to 1:1 as el!_cant) to aff:,rci the subtitle compaar.d (3.18g).
MS 313 (M.-: ~'-)U--ii"', ~ C0"9 ;
*rB

b) (1S-cis)-4-[[5-Amino-6-chloro-2-(propylthio)-pyrimidin-4-vi] amino] -2-cyclopentene-l-ol Iron powder (2.30g) was added to a stirred solution of the product of step (a) (2.61g) in acetic acid (100m1). The reaction mixture was stirred at room temperature for 2 hours, concec'-a.ted to half volume, diluted with ethyl acetate and washed with The organic phase was dried and concentrated to afford tl:P subtitle compound (2.28g).
NMR SH (d6-DMSO) 7.03 (1H, d), 5.93-5.90 (1H, m), 5.85-5.82 (1H, m), 5.05 (1 H, d), 4.91-4.85 (2H, m), 4.66-4.60 (1H, m), 2.94 (2H, t), 2.77-2.68 (1 H, m), 1.69-1.57 (2H, sextuplet), 1.48-1.42 (iH, quintuplet), 0.94 (3H, t).
c) (1S-cis)-4-[7-C;aoro-5-(propylthio)-3H-1,2,3-triazoio[4,5-alpyrim;din-3-y1]-cyclopentene-l-oi Prepared according to the method of exampie 6, step b) using tne product oi step b).
MS (APCI) 312 (iv1+h'''), 224 ( i u0%) d) (1R-trans)-rj [(2,4-Ibimc:thoxyphenyl)methyl~-2-pheni~i-c,yclopropanamine A solution of (1R-trans)-2-phenyl-cyclopropana.mine, [R-(R*,R*)]-2,3-dihydrox,ybutanedioat.e (1:1) (prepared as described by L.A. Mitscher et al., J. Med. Chem.
1986, 29, 2044) (1.92g) in IN aqueous NaOH (50m1) was stirred ;:or 10 minutes and extraeted with dichloromethane. The extract was dried, evaporated and the residue was dissolved in methanol (30m1). 'I'o this was added 2.4-dimethoxybenzaidehyde (i.12g) and the pH adjusted to 5 with acetic acid Sodium cyanoborohydrice (0.46g) was added. The mixtu.re was stirred overnight, basified with 2N NaOH and extracted with ethyl acetate.
The extract was nried, ev.xpo!-ted and l uriiieu (: iC,,,., me::sano::dic(aJ,rom(;thane: 0.880 ammor.ia 2: 98: 0.1 as eluaut) to afford the subtitle compound (1.10g).
NMR iiH (CDt:;i,) 7.2?-6.9 7(6Ei, m), 6.49-6.41 (2H, m), 7.73 (:s H, s). 3.69 (-'~Hi, s), 3.66 (2H, s;, 221-2.16, (1i<, in), 1.82-i.76 (1H, m;, 1,01-0.87 (21i, mj.

e) [1S-~1a.,4a;(1 ~' ,21?~~)]1- ~-t7-[CV [(2,4-Dimethoxypinenyi)methyl)-(2-3o phenylcyclopropyi)aminoj-5-(propylthio)-3fl=1,2,3-triazoloi4,5-djpyrimidlin-3-yl]-2-cyclopentene-I -ol A solu*.don o1 tne product from~: step (,c; (0.'73g), the prod'uct from step (d) (t7.'73g) and N,N-diisopronvlethylaminP (815 1) in 1,4-dioxane (25mI) was stirrPd at room temperature for 1 hour. "i he r.;actiozi .: ixture was concer.trated ar_c: the residue uril'i~:d ethyl acetate:
hexa:ifs :4 as eluant) to afford the subtitle compound (1.18g).
MS (.ypC:,) 559 (1V1+H+,100%) f) [1S-[1a,2(3,3p,4a(1S*,2R*)]]-4-[7-[N-[(2,4-Dimethoxyphenyl)methyl]-(2-phenylcycloprolry,l)amino]-5-(propylthio)-3H-1,2,3-tr;;azolo (4,5-d] pyrimidin-3-yl]-cyclopentane-1,2,3-triol To a s;,lution of the product of step (e) (0.50g) in acetone ( l Om' ) and wt.l,-r (;!r; )' was added N-methylmorpholine-N-oxide (0.38g) rollowed by osrnium tetroxide (390 1, 2.5%
solution in t-butanol). The mixture was stirred at room temperature overnight then treated with sodium hydrosulphite (0.90g). The suspension was filtered through celite and the product purified (Si02, ethyl acetate: hexane 1:1 as eluant) to afford the subtitle compound (0.22g').
MS (APCI) S93 'M+ri',:iGO%) g) [7tS-{ia,20,3p,4a(13'*,2R*)]]-4-j7-[2-(P'taenylcyclopropyi)amino]-5-(propylthio) -3hi=1,2,3-triazolo[4,5-rt]pyrimidin-3-yl]-c3,clopentane-i,l,: -trios Prepared according to the method of example 2, step b) usiag the product of step fJ.
Purification (HPLC, lvovapaV C18 column, 0.1 io aqueous ammoniurL
acEtale:acetonitrile, 60:40) er"forc'eci the ti 1P compCUnd (0. 12g).
MS (A PCI) 443 (M+.H+,100%) NMR oH (d6-DMSO) 7.29 (2H, m), 7.16 (3H, m), 5.11-4.91 (3H, m), 4.97 (IH, q), 4.67 (1H, m), 3.93 (1H, br s), 3.78 (lH, m), 3.22 (1H, quintet), 2.95-2.81 (214, m)). 2.58 (1H, m), 2.13 (1H, m), 1.91 (1'H., m), 1.5, (3H ,m). 1.31 ( lI-3, m;I, 1(3N, tl.

Example 13 2-[[[1S-[1a,3~,4~(1.S*,2R*)]1-3-Hyd.roxy-4-[7-[(2-phe.nylc,yclopropyl)ana.ino]-(prflpytthio)-3H-1,2,3==triazolo[4,5-djpy-rimydiu-.3-),1]-cyclopeiityl]oxyjace:ic acid, hemla:nmoezuni a) a~ISõ[1(x,4F.'")~j -41=~-(',- !~ N-õ2,4i~.i'~imet~t~.c~x~~~-F~'ax~y;t)m~~tii,Yl. .,1.
phc x-ylcy0copropva,,ai:iu]-5-(prAap3 itl+;ol-~~1.-1,:~,+-triaz ~l;~I a,S-11py'rimiilin-3-y1J- 2-cyclopen-kenyl] ~xy]a.ceti;: acid, 1,1.=darnethylethyl ester Tu u sGbitron of the I,roducr ijoni exanil;le I step (e) (1.LOg) ir; tolueiie (lumi) was added aqueous NaOH (5Cd, 10m~) followed by tetrabutylanunonium bromide (0.10,g) and the mix.t.ur:-, stirred *c: .3,, r,u:..:.tes. Dimethyl su;foxide (E70Lt1) and tert-butyl bromoacetate (3.47zn1) were added a.nd the reaction mixture stirred for 1 hour. The organic phase was washed with water and brine, dried and evaporated. The residue was purified (Si02, ethyl acetate: hexane 15:85 to 3:7 as eluant) to afford the subtitle compound (0.96g).
MS (APCI) 673 (M+H},100%) s b) 2 I i[1.~'= [loc,3~,4a(1S*,2R*)]]-4-[7-[N-[(2,4-Dimethoxyphenyl)metk.3'l]-(2-phenylcyclopropyl)amino]-5-(propylth io)-3-TI-1,2,3-triazolo j4,5-d] pyrimidin-3-ylJ-3-hydroxy-cyclopentyl]oxy]acetic acid, 1,1-dimethylethyl ester and 2-[[[1S-[1oc,2[3,4a(1S*,2R*)}]-4-[7-[N-[(2,4-Dimethoxyphenyl)metliyl]-(2-phenylcyclopropyl)aminol-5-(propylthio)-3H-1,2,3-triazolo [4,5-d]pyrimidin-3-yl]-2-io hydroxy-cyclopentyl]oxy]acetic acid, 1,1-dimethylethyl ester A solution of the product from step (a) (1.08g) in teti-ahydrofurail(15m1) at 0 C was treated with borane-tetrahycirofuran complex (1M solution in tetrahydrofuran, 8.02m1) dropwise.
The rt-actron mixture was stirrecl at G C for 16 hours. Ivletna.zoi was adeen t.na the mixture was stirred at roum temperature and then cor.centraced. 'I'he residue was dissolved in is digiyme (lOml) then rreatea with trimethylamine -N-oxide (0.48g). i'he rcaction mixture was meated at 130''C for 2 hours tiien diluted with ethyi aceiaiz and washed with brine, 1N
HCl and aqueous soaium bicarbonate, dried and concentratea. ;''urification (SiO2, ethyl acetatP: hexane 3:7 as eluanr) gave the two products:

20 (i) j(2,~4-.L~imethoxyphenyMlmet4~y1?-(2-phenylcyclopropy~.)amino "-5-(proayltMio)-3H-1,2,õ-triazo!.or4,F-d!pyrimidin-3-yl]-3-hydroxy-cyclopentylf oxy?a:cetic acid, y.,?_-dixnethy!.eth,y- ester (0.331Y).
NMR bH: (d6-I)r/tSO) 7.2'1-7.11 (SH, m), 6.98 (111. d), 6.54 ( lli, d), 6.39 (1 H, m), 5.23 (2H. br zn), 5.03 (lhl, d), 4.80 (3H, m)., 4.20 (1H, nl), 3.95 (211, s), 3.71 (3 H, s), 3.66 (3H, 25 s), 3.00-:~.90 (3H, m.). 2.65 (111, rri), 2,39 ;1H, br rn), 2.30-2.10 (21/'~, m), 1.95 (111, m), 1.60 (211, sex.tuplet), 145 ~ 1H, rn), 1.43 (913, s), 0.90 (3I4, t).

(ii) 2~ii'_.S-[1r,2;.~,~t~,l1.S*,2~~,:;~} 4 [7 ~~ 1(24..a~-iatrc~ h.r,a~ ptit rs;fiy;l] -(3., phera;y, n-3-y1J-2-NMR i1!J: (a6-Di~,~~SGt) 7=::7-7 11 (5:i-i, r. ), 6.98 6.54,'iD, c!), 6.40-6.36 (lH, m), 5.2? (2Ai, m), I.B9 lH, ci', 4.25 (11-1. rri", 4.04 (Z' s), 3.8 8 t;l~i, m;, 3.7J. ;311, s), 3.65 (3E; s), 3.00-2,.90 ;3tf. n:i), 2 n 7 1? H, n, rnõ 2.30-2.10 (211, m), 1.61 (2H, sextuplet), 1.44 (1 H, in), 1.43 (911, s), 0.91 (3H, c).

c) 2-[[[LS-[1oc,30,4cc(15-,!R*)11-3-Hydroxy-4-[i-[(2-phenylcyclopropyl)amino]-(propylthio)-3H-1,2,3-triazolo [4,5-dJ pyrimidin-3-yl]-cyclopcntyl] ox,y]
acetic acid, hemiammonium salt The title compound was prepared according to the method of example 2, step (b) using the prcdur, of step (b)(i).
MS (APCI) 485 (M+H+,10G?%) NMR 8H (d6-DMSO) 7.31-7.15 (5H, m). 4.78-4.68 (2H, zn), 4.17 (1H, m), 3.90 (2H, s), 3.20 (13-I, m), 2.97-2.8 a(2H, m), 2.65-2.52 (IH, m). 2.25-2.1I(3H, m), 1.92-1.85 (IH, m), 1.55-i. ~a (3H, m), L34 (Iri, m), 0.8i (sri, t).
to Example 14 2-[[[1.i-[1oc,20,4a(1S*,2IC*)]]-2-Hydroxy-4-[7-[(2-phenylcyclopropyl)aminoJ-5-(propylthio)-3H=1,2,3-triazolo [4,5-d] pyrimidin-3-ylJ-cyclopentyl] oxyl acetic acid, hemiammonium salt The titlt-, compound w,as .~r.:;=:are,di ac~nrding to the t:?:thod c;f exarnpie 2 step (b) using the product,-A step ;b; (i: ).
MS (APCI) 485 (iV1+Tr,100%) Nlvlk .''iri (d6-DMSO) 7.31-7.16 (5H, m), 5.21 (1H, quintet), 4.28 (1H, m), 4.03-3.92 (2H, m), 3.82 (1H, m), .a.19 (iH, rr.), 2.96-2.83 (2I-:, ni), 2.64 (itl, rn), 2.41 (lii, m), 2.16-2.08 (311, m,,, "t.54-1.4! (3H, m), 1.33 (1H, in), 0.82 (3H, t).

Example 15 2-1-j.1S (lc~u ~,~~~,'rth}~-~w-,1-(1tllit?Jlunukr;o)..:~-(propylti:i,)-~i1:~:1,2,~ firio,tolo[4,5-d]pyrtnsidin-3-=ylJ -~,3-t1ih;~clra:cy-cyclupentyi]axy]aze.rc uwiu a) 5,'?-13is(propyltlti.;,)~,1.f1'=1,2,3-triazr+lo[a4,e-dipyrianidiae A rr.ixt.;ir3 of 4,5-diumino-2,6-dimerc2.ptopyri.r,+.udine (25g), potassium hydroxide (36.9g) and prc~pyl iodide (52.'9mI) in water (710m1) was stirred for 72 hours. The product was collected by filtration, washed with water and dried. The materiai was taken into water (71um?'ul;lacial nc,etir. ticid (710m1), ,~ooled to 5 C amd. a solut+or. tJ s~-7d.ium nitrite (9.38g) in w ate_ i ad,iec: , n:aintair.:r:g tRe terrrperatt<re beio,u 5' C. '1'he rruxture was allowed to reach room t,~rr-perature and tne product was collected by iilrration, washed with water and ~r~,zc~ (28.9g).
Mr (F.I! %6:S- ('N/1') b) Mixture of (1S-cis)-4-[5,7-bis(propylthio)-3H-1,2,3-triazolo[4,5-dJpyrimidin-3-ylJ-2-cyclopentene-l-ol and (1S-cis)-4-[5,7-bis(propylthio)-2H-1:,?.,3==triazolo [4,5-djpyrimidin-2-yl]-2-cyclopentene-l-ol To a solution of the product from step (a) (3.7g), (1'3'-cis)-4-ace'ioxy-2-cyclopenten-l-ol 5 (2.0r;; ~:nJ triethylam.ine (6m1) in THF (100m1) at 60 C was added tetrakis(triphenylphosphine)palladium (0) (2.Og), as a suspension in THF
(50m1). The reaction mixture was stirred at 60 C for 4.5 hours and purified (Si02, ethyl acetate: hexane 1:3 as eluant) to give the product as a 2:1 isomeric mixture.
MS (Al'CI) 352 (IVI+ri ",100%) c) f3alt-(3aa,4(x,6a,6aoc)jl-6-(5,'i-Tiis(propylthio)-3H-1,2,3-triazolo[4,5-dJpyrimidin-3-y1]-tetrahydro-s ,2-uimettiyl-4H=cyclopenta-l,3-ciioxol-4-ol A rr,ixture of the prouuct frorn step (b) (2.Og), 4-methylmorpnotine-N-oxide (1.27g) and osmiuin tetroxide (2.5% solution in tert-butanol, 2.9m1) in acetone (110mi) and water 1s (25m1) was stirred at room temperature for lti Yiours. Sodium ttydrosuitite (Z.Og) was added and tht mixture vr3s stirred for I hour then filtered through celite. washing with ethyl acetate. The combined filt.rates were concentrated and the residue dissolved in acetone (75m1). Tosic acid (1.08g) and 1,1-dimethoxypropane (6m1) were added and the mixture was stirred zor 1 hour, 'i"he solution was concentra.t.ed ana tne residue was Dardtioned between ~ ichloromPthane and water. 'i'rLe organic phase was drPd. and concentrated and the residue purified (aiC2, ethyl acetate: hexane 1.:4 as eiuant) to give the subtitle compound (1.0r3g).
MS (APCI) 426 (1Vr-+-l'r',100%) d) 2-j[f3aK-(3aa,4cc,6a,eaa)J-6-[5, 7-13is(propy,lttii,~,)-3I3'-l,2,3-triascoio[4,5-d] p;r,ri r:lidin-3-yl J-tetrairw slro-?,,".-cl;ni ethyl-4H-cyclopeQ ta-1. 3-cliox ol-4-y1Joxy]acetic acid, l ,:1-dirvtetLy.le 'h~,l evVr To a-,t:1.ua:ion of ine }'roci.L .:t from step (c) ;0.36g ~r: i:f-L?- 1;10~~~
:at (t C .j as added sodium hy(iridc A 60% in oii., "~7m1;). The miy:rure was Srirred at 0 C fc,- 1 -55 rnim,res, and tert-butyl brorr-acetate (t). 14:Ij) %';zs adcied. T;~.-, mixtcte was st:rre~d at ri-omm t.:emperatu.re for 24 hours and purifieri (Sit)?, t- tt,yl ace:t.ace: hexa.r.P 1:10 as e3:zart) to give the subtitle compound (0.16ky).
MS (A.YCi) 482 (lVla-H " 1()0%) e) 2-[[[3aR-(3aa,4oc,6oc,6aa)]-6-[7-(Butylamino)-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-v1]-tetrsthydro-2,2==dimethyl-41Y cyclopenta-1,3-dioxol-4-yl]oxy]acetic acid, '1,1-dimethylethyl ester A mixture of the product from step (d) (0.15g) and n-butylamin:. (5ml) in 1,4-dioxane Mia1; -v.,a.; stirred at room temperature for 1 hour, concentrated and purR',ed 'Sin2, ethyl acetate: hexane 1:5 as eluant) to give the subtitle compound (0.14g).
MS (APCI) 537 (M+H{,100%) f) 2-[[[1S-(1(X,20,3;3,4a)1-4-['1-(Butylamino)-5-(propylth,o)-3H=1,2,3-triazolo[4,5-1o d]pyr'imidin-3-yl:1-'l,3-dihydroxy-cyclopentyi)oxy[acetic acirt The product was prepareci according to tne method of example 2, step (b) using the product of step (e).
MS (ESi) 441 (M+H+, 100%) NMR SH (d6-DMSO) 9.01 (iH, t), 4.94 (iH, q), 4.53 (iH, m), 4.v4 (2H, m), 4.00 (1H, m), 1s 3.85 (iH, m), 3.50 (2iri, q), 3.08 (2H, m), 2.64 (1H, m), 2.08 (1H, m), 1.65 (4H, m), 1.34 (2H, m ), 0.99 (3H, ). 0.91 (3H, t).

Exampie 16 2-[f[1.S'-Ila,2[j,3(3,4(y.)]-4..f't-(Ilutyiannsno)-S-(propylthio)-3ff-1,2.3-triazolo[4,5-2o d]pvrirnidin-3-y1]-2,3-dihydroxvcyclopentylloxy]acetamide To a sclution of the product of example 15 (0.21g) in N,N-dimethylformamide (25m1) was added a solution of ammonia in acetonitrile (5m1) and bromo-tris-pyrrolidino-phosphonium hexatlucrcI,ho, pt:a.~e l:e= rnrixture vtia.sdrred for l G;r!i~su:es und N-25 diisoprop: lettryxa.rn'n!-, (3~'~Cp l) was add,=;d. The reac.+ion n:.i:ttur+: was stilred at room tempem;ure for 2 hcurs. roacent:-ated_ 4 n d purii7ied (Sep-pak C18 silica, water to aeet.onitriie gradieut eiutioL, rollowed oy HF'f,(-', Nw~ a-pak l,l "E, colulnII, C. l% aqueous tri;:aor,;acet.ic aci,i:,:ceto*.itrile 50:50) to give the cit:e co:npounc.
(0.09g).
MS (APCI) 441 0 (M-. 1 0(}%) 30 NiviR C'H ;d6-DM.'3C, 8.9' ; iH, t), '.33 (1H, br s), i 18 (1H, br s), 5.20-5.10 (2H, br s), 4.95 (?..*=I, q), 4.57-4.53 lIH, m), 4.04-4.02 (11ri, m), 3.88 (2H, s), :3.81-3."i9 (114, m), 3.49 (2H, q), 3. i 1-3.d6 (211, in), ~.l(t-=2.60 azid 2.15-2. )i(i i,, ni;, 1.10 2fi, sextet), 1.63 (2H, qu:ntet.õ l.:34 (2ti, i1.99 (3H, t), 0.9: (j:ti, t) Example 17 [1S-[l a,2 (3,3[3,4a(1S*,2R*)]]-4-[ [5-(Methylthio)-7-[(2-phenylcyclopropyl)amino]-3H-1,2,3-tr+.azolo [4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol a) [l,S-".r,20,3~,4oc(1S*,2R*)]]-4-[7-j(2-Phenylcyclopropyl)arnino]-5 =
(propylsulphonyi)-31'~'=1,2,3-triazolo [4,5-d] I;yrimidin-3-yi]-cyclopentane-1,2,3-triol Prepared according to the rnethod of example 4, step k(a) using the product of example 12.
MS (AYCI) 475 (T/I+:EI+, 100%) b) [YS-[loc,2~i,3p,4a(IS'9,21t*)]]-4-(t5-(1Viethylthio)-7-[(2-phenylcyclopropyl)amino]-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yl]-cyclopentane-1,2,3-triol Sodlun, tiiiomethoxide (0.11g) was added to a solution of ti7e product of step a) (0.34g) in THr (2orril) ana tne reaction stirred tor i hour. Ihe reaction mixture was concentrated and is the residue purified (SiO2, ethyl acetate as eluant) to give the title compound (0.20g).
MS (AYC:r) 415 (ivT+H',i(1u%) NNTR bH (dc,-DMSQ) 9.36 (1K d). 7.31-7.16 (5H, m), 5.11-5.10 (1H, m), 5.04-5.01 (1H, m), 4.97 (1H, d), 4.94-4.93 (1 H, m) 4.68-4.63 (1 H, m), 3.94-3.92 (1 H, m), 3.79 (1H, s), 3.21-3.18 (ili, rn), 2.62-2.5i (IH, ni), 2.32 (3H, s), 2.15-2.11 (if=I, m), 2.14-2.i0 (2H, m), 1.94-1.;s'1 (lH, rn), 1.51-1.17 (ih, m), 1.36-1.32 ;iH, m) Exampie 18 [1S-[1ct,26,3[,334cf,i1~'*,2A*)]:a_4-~5-~(rilethyiethyl)thio]-7-[l2-phci:, I(.-vclopropF,ri)arniirc?-3K 1,2,3-triazolo[4,5-dlpyrimidin-3-yl]-cyclopentane-1,2,3-2s triol Prepared according to the method of example 4, step (b) usin; the product of example 17, stel, (a; .
MS (AI=f :;;) 443 (?v1+ :r, i!1(?%) NMR riti (d6-DMSC)) 9.38 (1.H, d), 7.31-7.16 (5H, m). 5.11 (111, d), 5.04-4.96 (1H, m), (lj-i, rrl), 3./9 ~IH, s}, 3.u1 {lil, sept) 3.2 ~-3.: ;; ( i 1~, ~t:), ~.~~:-:%.~7 ;1H, rr,.), ~:.11-2.i)7 ,;ll-i, n=~), 1.93 i.8> ( lki, m), 1.6G-1.54 (1H, rn), 1.38-1,30 (1H, m), 1 ?.3 (314, d), 1.07 (Y-I, d) Example 19 [1S-[ltx,2P,3(3,4a(1S*, 2R*)]]-4-[7-[[2-(4-Fluorophenyl)cyclopropyl]amino]-5-(propywth io)-?H-1,2,3-tri.azolo [4,5-d] pyrimidin-=3-yl]-cyclopentane-1,2,3-triol a) (1~'==.-i,~)-Eis(1;1-di.methylethyl)-4-hydroxy-2-cyclopentenylimidodicarli:)Icrte To a suspension ot etier washed sodium hydride (60% dispersion in oill 0.31 g) in THF
(30 ml) was added imidodicarbonic acid bis-(1,1-dimethylethyl)ester (1.84 g).
The mixture was stirred at 40 C for 1 hour. To the mixture, at ambient terriperature, was then added (1S-cis)-4-acetoxy-2-cyclopenten-l-ol (0.5 g) and tetrakis(triphenylphosphine)palladium -o (0) (0.185 g). 'The reaction rr,ixture was stirred for 24 hours tnen purified (Si02, ethyl acetate: nexane 1:9 as eluant) to give tl:e subtitle coriipound as a coiourless solid (0.9 g).
NMR SH (d6-DMSO) 1.43 (18H, s), 1.61 (1H, ddd, J=12.3, 7.7, 6.4 Hz), 2.54 (1H, dt, J- i 2.6, 'i .4 Hz), 4.51-4.5'i (1H, rn), 4.86 ( i H, tq, J=8.0, 1.8 riz), 4.9 i( i ti, d, .i=5.4 Hz), 5.71(2H, m).

b) [1R-(ke,.,2[i,3[3,4(x)]-2,:3,4-Trihydroxy-cyclopentenylimidodicarbonic acid, bis(1,1-dimethylethyl) ester The subtitle compound was prepaxed according to he method of exampie 12, step (f) using the product of step (a).
2o NMR 5M r'a5-i7MS0;l i.44 (1. 8& s), 1.46-1.60 (11-i, rn), 1.97-2.05 (1 H, rn). 3.55-3.58 (1 H, m), 3.66-3.73 ( lh:, r?:z), 4.. ).1-4.21 (LH, m), 4.54 (1 H, d, J=4.8 Hz), 4.56 "1 El, d. J=5.9 Hz), 4.82 (1H, d,.i=4.6 Hz) c) [1S-{loc,:zfj,3(i,4c:)1-4-[["'-Chloro-5-nitro-'2-(propy[tthi.o)-pyri.no.idin-4-y)IJamino]-2-2s cyciopentane-', z 3-irio:
A mixtuTe ot t.ie proauct o; ;telp (b) (0.68 g), tirezhano). (10 rn[) and i).yc.rcc.hlcric acid (2M;
5 n:J) was stirred for 24 hours then concentrated under reduced pressure. To the residue was adu,.:i T.riF (10 aii; anr:lJ,lti'diisor~4 ty)ethyl4~rrine (1.'78 inl; by :',6-dichlcyro :)=-r-i;;t.ro-'L,-(pi,opyittYio)pyriniidlne (preparea as describe :
i:. VVU 97t;3034) (0.82 g).
30 The rriixture was heated at reflux for 201-iours theri ccoled and concentrated under reduced pressurF;. Th residuE: ww= ~urified (5i02, ethyl ac;t;ce: :z: x.ant: 7:.3 , ;s e} az nt:;t give the sulatitl?t r.oa-npound as a yt;i ow solid (0.41 g).
Mj (Art::i: i65,13-67 ~,M-i-W,1009r'-d) [1S-(1a,2P,3(3,4a)]-4-[[5-Amino-6-chloro-2-(propylthio)-pyrimidin-4-yl]amino]-2-cyclopentane-1,2,3-triol The subtitle compound was prepared according to the method of example 12, step (b) using the product of step (c).
MS (I,,pCI) 335/337 (M+H},100%) e) [1S-(1ct,2J3,3(3,4a)]-4-[7-Chloro-5-(propyithio)-3H-1,2,3-triazolo[4,5-dlpyrimidin-3-yl]-cyclopentane-1,2,3-triol The subtitle compound was prepared according to the method of example 12, step (c) using io the product of step (d).
MS (APCI) 346/348 (M+H+), 318 (100%o) f) [3aS-ri(E),3aa,6a,7ap]]-1-[3-(4-Fluorophenyl)-1-oxo-2-propenyl]-hexahydro-8,8-dimethyl-3H-3a,6-methano-2,1-benzisothiazole-2,2-dioxide A mixture of 3-~4-tluorophenyl)-2-prof,enoic acid (3.0 g) and tnionyi cdioride t5.0 ml) was stirred a-. 70"C for 1 nour, the reaction mixture was then concentrated u*tder reduced pressure. The residue was azeotroped twice with dichiorometriane then dissoived in toluene (10 ml). To a suspension of sodium hydride. (60% dispersion in oil; 0.99 g) in toluene (40 ml) was added a solution of [3aS-(3aa,6a,7a(3)]-hexahydro-8,8-dimethyl-3H-3a,6-metha.nc--2,,1-benzi.sothiazole-2,2-dioxide (3.89 g) in toluene (40 ml) and the mixture stirred for 30 minutes. 'I'o the reaction mixture was then added ttre solution described above and tre resultir.g suspension was stirred for 16 hours. Water (100 rril) was added, the organics collected ard the aqueous extracted into dichloromethane (3x100 ml).
The organi(.s were combined, dried and conc:;ntrated.. ~errystallisE tiorr :. : Aa r.nol) gave the subtitle co:.nl)oand a,~ co,ourless needles (5.92 g).
MS (A1'CI) 364 (1~4+H-,11JJ%) g) ":SaS= [1(Y.S'*,:zS*),3aa,~.~+a,7a.b] ;-1-[[2-(4-F7uorophenyl)cyclopropyl],-~arbonyl]-hexahyd ro-.t?,8-ditraethyi-3H-3a,6-methano-2,i-ber..zisothxazole-2,2-dioxide A soiucion o: diazc,-rif,d)are iYi ether (1:5D rnl? (prepared tr deqcibed H
Vogel's texto-,,o;co: r.racticai ocgru:-.c chemistry, fifth edition, Longman scientific and technical, p432) -%vas a.adecl s.;i a Fohit:ton or the pro(iucr, c. r step ?f );5.9(? g) an6 1) acetate (18 nag; in dAchloronietiaane (350 ml j at 0 C arid the reaction mixture sti*.Ted at 0 C for 5 hours. Acetic acid (5 ml;r was added and the reaction mixture was then washed with saturated soda.um bicarbonate solution (200 ml) and the organicr, filtered through a plug of silica. After conccntrating in vacuo, the residue was recrystallised (ethanol) to give the subtitle compound as colourless needles (3.81g).
MS (APCI) 378 (M+1i+,100%) 5 h) (?.R= trz.ns)-2-(4-Fluorophenyl)-cyclopropanecarboxylic acid A suspension of the product from step g) (3.7n, g) and lithium hydroxide monohydrate (4.11g; in tetrahydrof-arar: (100 ml) and water (3 rnl) was stirred at-S0'C
for 24 hours. The reaction niixture was concentrated in vacuo, and the residue dissolved in water (100 ml), acidified with 2N HI;Y and extracted into dichlorometnane (3x751ni).
io The organics were dried and concentrated. Purification (Si02, isohexane:diethylether 2:1 as eluant) gave the subtitle compound as a colourless solid (1.78g).
MS (APCI) 179 (M-H+,100%) i) (IR-trans)-2-(4-)H'luorophenyl)cyclopropanamine 15 To a solution of the product from step h) (2.6 g) and triethylamine (2.7 ml) in acetone /water (10: i, 33 ml 'i aY 0"t: was added ethyl chioroformate (2.0 ml) over 5 min. 'The soiution was maintained at 0 C zor 0.5 h before addition of sodium azide (1.52 g) in water (6 ml;. After a. further hour, water (350 ml) was added and the reaction mixture extracted with toluene (3x10(1 mi). "I'he organic extracts were combined and dried, then heated at 20 rer+.ux for 2bonrs bPnind a blast screen. After c.oolin? the solution, 6N
HCl (50 ml) was added a.nd the mixture heated at reflux for 3 hours. Water (150 m?) was added and the aque.otT.s phase basi.f..cr:d with '2N:Na(.-H (a.q), then. exrra.cted into dic Yr~111-nethine (3x100 mi). 'i're nro'anic pnase was driea and concentrateci to give thP subtitle compound as a colnu .rie,ss oil 25 Nlv.R iiH (CUCl3 j C?. 88-0.95 (1 H, m), 0.99- "t .06 (1 H, m), 1.81-1.87 (11 T, m),. 2.47-2.52 (ffi,cr,), 6.90-'1.00 (4P.i, r,) j) 116~-11 a,L-4-['i-[!%-(4-Fluuropac-nyl)cyilapropyljamino]-5-(pz'o~~yatlxiP~1-:~f3-1,:,,3-tr~atolc-[~l,S-tf],~yrimi lin-3 ~1]cycloper~tane-~,'l,3-triol 30 Tiie title corapoui"+.d was [irP,pared acc,orciir.g to ' hE~ raethoci of.
~xurnrle 12, step (e) using the prcrs,~c;:s -)f st;:lz !z,i and s~*cp (i.).
Ivily tj k l't:li 4 61 i.rf---W', :4C:P%;;
N.Nii7 :j+i (dti-UVSC-) 0,99 (3H, t, j--7.2 1-1z>, 1.29-t. 15 ni), 2 55-L.63 (1 ff, m), 2.81-3. J. 3(2R, m), 3.14-3.3>( I'H, rn), 3.78 (1 H., br s)., 3.93 (11"1, br 4'.
4.66 (1 H, br s), 4.92-5.12 35 (411, r:_)., 7,11.='7 1.26 (4H, in), 9.33 (lH, d, J=4.2 Hz) Example 20 [1S-[1a,2(3,3P,4a(1S*, 2.tyx)11-4-[7-[[2-(4-Methoxyphenyl)cyciopropyllamino] -(propylthio)-3H-1,2,3-triazolo [4,5-dj pyrimidin-3-yl] cyclopentane-1,2,3-triol a) ['_f?,=i'rcns)J-3~(4-Methioxyphenyl)cyclopropane carboxylic acid To a solution of dichloro(p-cymene)rutheniu-n (II) dimer (250 rrig) and 2,6-bis[(4S')isopropyl-2-oxazolin-2-yl]pyridine (240 mg) in dichloromethane (150 ml) at room temperature was added 4-vinylanisole (25 g). To this solution 'was added ethyl diazoacetate (5.0 g) over 6 hr. The solution was maintained at room temperature for 18 hours then diiuted witt, i-tiexane (Lit) ;rii j and passea through a plug of s:.lica (50g) with a further 250 ml o: 1: i i-hexane/diciilorometrrane. 'I'he ziitrate was concentrated and the residue dissolved in methanol (100 ml) and LiOH (4g) in water (10m1) added, the mixture was then refi'uxcd for 4h. 'I he resulting solution was con:.entrated to give a coiourles; .;ulid which was washed with 1:1 ether/i-hexane (100 mi). 7['he soiia was then tri turatea with 2N HCl is and the precipitate coiiected to givc; the subtitle coiripound (5.06 g).
MS (AP(---t) 191 (1V[-H'-, 100' o) b) [l.lx-(trans)), -2==(4-Methoxypheuyl)cyclopropanamiine, Jk-(R*,Rr)1-2,3-dihydroxybutaneclioate (1:1) The am?ne was prepared a.ccording to the method of examnle 19, step i) using the product of step a). The amine was dissolved izi. ethanol (5 ml) and a solution of L-tartartic acid (035 in ethanol (5 ml) was added. After 20 minutes the solid was, collected and recryst.a)lzsec4 (isopropar.ot./water 3:1) affordina the subtitle comnoun.c'.
as colourless nee;..'es M.n. 152-3'c,.
Nl\,R. 3,1' rct~ :'~ viS ~~) -7.95 (2H, d), E; 85 (211, d,, 3.91 (211, s), 3.77. ',.'.i, 5), 7.70-2.60 (1H, m), ~.15 2.u7 (.lIl, rn) 1.2:.1Ø;, jH,?ni, 1.63 (Ji, iu.) c) -1t;:-(4-~4etho:%vplleu -i,cyc.it:propy)jo rminoj-5-(praf)y;lthio)-"3H-i,',:,'-~-tr,.aznlLt[~L,'9-rlll}yrimidi_1-3-,v1t .cyc[openxari:-1.; ,!,,3-triol 3o Th,-, tide ;,oml:ound was prepared according to tne. rr.ethoe~. o' Exarnpie 12, step (e) using the procluc~: ;:f step (b ~.,jd ;r.o. -rociuct of' example 19, step ;e).
MS (Ar'Cx) 473 (P/I+Ei 1 JGaIo) ~'~.33 (3H, t. J..-'7.2 riz). ?.i)-2.23 t tia, .-.d). ;1H, m), 2.81-3.04 (11=a, r,i).: 3.06- :.17 ("4, ni), 3.33 (::")H, s), 3.73 (IH, br s), 3.91-3.98 (1H, in), 4.60-4.70 (1H, m), 4.90-5 1 3(4H, rri), 6.86 (21;, d, J=8.7 :Hz), 7.14 ~12.H, d, J"-=8.7 I-Jz), 9.30 (1H, d, J=4.2 Hz) Example 21 [1S-(10:,2 (3,3 P,4a(YS'*,2R11)] J-4-[7-[ [2-(4-Methylphenyl)cyclopropyl]
amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d] pyrimidin-3-yl]-cyclopentane-1,2,3-triol a) (1R=-trdns')-2-(4-Methylphenyl)cyclopropane carboxylic acid Prepared according to t:he :-rethod of Example 20, step a'i using 4-met.hyl-l-ethenyl-benzene. MS (APCI) 175 (M-H+, 100%) b) (1R-trarrs)-2-(4-Metihylphenyl)cyclopropanarnine, [X-(CZ*,R*)]-2,3-dihydroaybrntanectiioate (1:I) Prepare(A according to the method of Example 20, step b) using the product of step a).
NMk 6H kd6-DNiSU)7.08 '2ri, d), 7.00 ~'21-ii, uj, 3.98 (2H, s), 2.'i5-65 (1H, m), 2.50 (3H, s), 2.30-2.20 (1H, iIl) 1..',l)- .:ul (iH, Iri), i.i)'I' (12'1, (].G) c) (35-!l.c.,25,3p,4a(1S*.2R*)]]-4-[7-[[2-(4-Methylphenyl)cyclopropyl]amino]-5-(prolpvlt?r io)==3S- p ,2,3-fir;pzclo [4,5-(~pyrir.nidin=-3-yl]-cyclopentane-:4.2,3-triol Tt.: 6mt1 ~-.:,,mpcund wis Fr~r?ared according to the method of ex~ mple 1, step (a), using the pr~,~ai:~~-is o'step (b) and. exarr..pl.P 19, ltep (e').
MS t;
r~ " t ' ~ c, ~~ i ~,r rx?r. t " 1..a .
NN;.. .iaa ~.W;-~~ ,1."~,y H~, ~~-~} ,L'~ (lf-t, rr.), (1::, :=n), 1.50 and 1.70 (2H, sex, J=7.2Hz), 1.87-1.94 (iH, m), 2.07-2.'12 (1H, m), 2.27 (3H, s), 2.54-2.61 (11'=:T, rr)), 2,82. 2 ~'-r 3.15-2.17 ('.'i.. 7n1, 178 (iu, br s). 3.93 rlu,T
s;, 4.66-4.67 (1F m' 4.91-5 1' (4tJ,; nl),. 7.09 014, rr s), 9 ?5 ('.H, br s) ExwrnpYt 22 [Y3-rlo,,2~,3[i,4o:(1S*, cR" )1]-4-~ 7 -[[2-(4-1:liloroplr(~ny1)cyelopj=opylJa~;auinu]-5-.
(prc,p=yltbiu)-3H=1,2,3-xriazulo j4,5-d]pyrimidin-3-ytj-cyclopentane-1,2,3-triol a) [1R-jl.oc(S*),2p]]-N-[1-(4-C:hlorophenyY)cyclopropylJ-2-methoxy-2-phenyl-acetiamrdc aud l,iiaropaenyl)cyc.opro~pyi]-Z-crle-innxy-2-phe,: ~ 1-iu~~2trraid ~
added to a solritizv~ of (S)-o, nzet'~:ox} ctzenylacetic acid (2.09g)>.r. dichloromethane (100m1)/DMF (!Oml). The reaction mixture vias stirred at roort,. te,-~rperzture for 4 nur.:~ the,i concentrated ar.ic the: residue a7,eorxoped with WO 99i05143 PCT/SE98/01393 dichlorotnethane (3xl0m1). 'The resulting oil was to-ken into dichloromethane ( 4m1) and treated with a solution of 2-(4-chlorophenyl)cyciopropylamine (Prepared as (tescribed by C
Kaiser etal J. Med. Pharm. Bul., 1962, 5, 1243) (1.86g) in pyridine (8mi).
T;:ze reaction mixture was stirred at room tempera'ure for 30 i-run9ites then partit'oned between dic'.-'::,-3c: ~than.e=( 500.n?) and water (500m1). The organic phase was dr'.
d zki3 concentrated and the .residue purified (Si02, :~ohexane:ethyl acetate:acetic acid 66:33:1) to afford [.S-[la(R*),2(3]]-N-[2-(4-Chlorophenyl)cyclopropyl]-2-methoxy-2-phenyl-acetamide (1.23g) MS (Al'C1, negative ionization) 314 (Ni-I-f ', 100%) io Further eiution of the coiumn gave [11 R-[1a(S*),2ji] j-l~=[2-(4-Chloropnenyi)cyctopropyl]-2-methoxy-2-phenyl-acetarnide ( I .4Gg).
MS negative ionization) 314 (Ni=r1'', 100%), b) (1,K-trans)-2-(4-Cir<lorophenyl)-cyclopropanamine A solution of [1R-[la(S*),2p]]-N-[2-(4-Chlorophenyi)cyclopropyl]-2-methoxy-2-phenyl-acetamice () ..l0g) (pre.nared as descr.ibed in step (a)) in 1,4-dioxane (20rn1) containing 5M
HCl (z.q) (40nii) was heated a~ reflux for 18 hours. The reaction vvas concent-ated and the residue part?tioned between water and diethyl ether. 'I'he aqueoiis phase was treated with 2M aaueous sodium hydroKade sohitiun (100rn1) then extracted wi*.h. diethvl ether (2x1U(-ml) '['he orga~~.c phase was concentrated to afford the subtitle compoiind (0.55g).
Optical rotation -J38.3 (c=0.2. methanol).

c) 1, ?.S-[1 a.2(3,3P,4a(1S*,2R*)j 1-4-[7-[[2-(4-Chlorophenyl)cycyopropyl]amino]-5-(P.~opy: t:~ kp)-3:1x=1.,2;3-tri ~az:r.+to[?,5-d ; ~r,~~ri.1: , :n. ~..yl~-cyclopenta;a w-l.,i,3-triol The title compound was prepared according to the aie.,hod of example 12, stet) (e), using the pr+l~(l+.('ts 4f stel+ (b) anrl ,-,'t.arnr)le =' 9, step (e).
MS (: ,,iJ'C.i) /4'79 (11,1+f 'i(10%) NMP. hH (dy-DMSO) 0.99 (3H, t, J-7.211-1z), 1.30-1.40 (1H, m), 1.48 and 1.68 (2H, sex, J=7.26z.), 1.52-1.60 (lH, w). (;If, I1llj, 2.1,~-2.15 (1H, m), 2.50-2.60 (1H, m), 2.16-:".1 'i (2'~l, ni), '?.i 3-3.?,' !l:H, Tr;, 3.?3s), 3.4~ '1F1. '.~zc), 4 6)-4.68 (1H, m), (4H.. C Ti. :t T-= .4 9.3 f ( ~ Z '~5) . , , Example 23 2-[-[LS'..'iltx,2(3,30.4cx(IS*,2R*)])-2;3-Dihydroxy-4-r7-[(2-phen.ylcycloriropy1)amino]-5-(propyflthio)-3,Fi'-1,2,3-triazolo[4,5-r1]pyrimiclin-3-1,,1]-cyc;loprrltyl.]oNy;-acctamide a) [sa~- [3aoc,4a;6a(1R*,2S*),6a(x)]]-6-[7-[N-[(2,4-Dimethoxyphenyl)_t-e-Lji-(2-phenylcyclopropyl)arnino]-5-(propylthio)-3 .r-I-1,2,3-triazolo[4,5-djpyrimidin-3-yt]-tetrahyd ro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-ol To a solution of product of example 12, step (f) (4.50g) in acetone (100m1), 2,2-dimeti.oxypropane (12.60m1) andp-toluenesulphonic acid (2.34g) were, added and the reaction mixture stirrea tor I hour. Purification (SiOL, ettiyl acetate:isoiiexaiYe 2:7 as elualct) artorded the subtitle compound (4.34g).
MS (APCI) 633 (M+H100%a) b) 2-i[[3aR-i3a,4a,6a,tiaoc(1RI~,,'lS*)Jj-6-[7-JN-(2,4-Dimethoxypheiryl)metbyl-(2-phenyycyclopropyl)-aminoJ-5-(propyYthio)-3t1=1,2,3-triazolo[4,5-dJpyrimidin-3-yl]-tetra.hvdro-2,2-dimethyt-4H=cyclopenta-Y,3-dioxol-4-yl]oxy]-acetic acid, 1,1-dir=set't9yleti-llym ester To a sov.t.on ff prodrer cz stel? la? (().40g) in toluenr (3.00.*nl) wem adr.ift~d SM NaOH
(3.00nn1) anct tetranutyiammoniutn oromide (31mg). The reaction mixture was stirred for 30 r-1inutes, then dimethylsuiphoxide (0.18m.1.) 3r.d 1, 1 -dimAthylethvl-2-hrornoacetate were added )rtd stirring continued for 4 hours. The toluene layer was separated and concentrated.
Purif.'catuon,;: iO2, ethyl ac,-.tate:isohexane 1:3 as elvant) aftoraecl the subtitle compound (G.41g), MI's i:.1':~l)'i47 (aV1+H ,IOtJ%) C) -=pA(Y,2 f"..-I lMtl Iiihy t;;1";XY-w_[(y_if_~'3..
phen'yl: yeloornls,yl)amin~]-5-(propylthio)-3H=1,'2,3-triazoto[4,5-d]pyrimidin-3-yl-cyc:rupent-1-y.) oxy] acetic acid The ;'lliJtlzt: -.')iT1p0L1ntiI waS prt",T)urt.'Cl ~.cCordLln to T.r.C
ITlettlod Oi' P,.:~~tZli ~~P 2, StF'J) ( b).
Niu 'c:l'F;,I) 501 (10.+I7 ,lOl)7o) d} -I?ris=[;.a,2(j,:~~,4c.(1.S",2.~,*}];-?,3-I~ihtidrax~-4-[?-[(2-~hei~g~i'ca r4py1)amino]-5.(f;

:-:1;0. v -71:tUf JC ~:_ki1II1piE 16 v.s?rsg'_h:; pIOd'LK'i lA
(t iE''-C ,N )~=aFak"' C18 ;olumn, 0.1 ,o aqueous ammonium .:cetz:te:acetonitrile, 6:3.3"

WO 9919:i143 I'C'1"1SE98/01393 40 MS (APCI) 501 (M-t-H+,100%) NMR EEI (d6-DMSO) 9.35 (1H, d), 7.33-7.16 (7H, m), 5.20 (2H, br m), 5.00-4.90 (1H, q), 4.55 (lH, m), 4.05 (lH, br s), 3.85 (2H, s), 3.80 (IH, m), 3.20 (1H, br m), 3.15 (IH, m), 3.00-2.90 (lH, m), 1.91 (1L, m), 1.51 (3H, m), 1.31 (1H, m), 0,31 (3H, t).
Exadx:ph-24 ~,2~,3(3,40~.(1~*,2~~*)]]-'4-[7-[[2-(3-Methoxyphen~rl)cycld}~ropyl]arninoj-5-(propylthia)-'3 11-=1,.",,3-triazolo[4,,!-alJp3irimidin-3,=yll-cyclopentane-1,2,3--triol a) f3aR==(3aa,4a,6a,6aa))-6-Amino-tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-ti., hy droclilor;de The nroduct from example 19, step (b) (17.37g) in 6M
HCI (100m1) and rnethanol (500rn1) was stir- d for 18 hours. The mixture was evaporated and then azeotroped with toluene (4 x 2',,lnrr,l1 .'? ~.'=/~ a ro!'?".r'FsF p')v/:iel' "S.'S r~P.') T}?ls sC,iO
was su$D<'.=rj.d?d 'J1 rC'tc'ne (250m1) is conta;nir? 2,2 -,l:me'! -)n yrroranf, a.Pf~ ,-onc. HCl (0.2m1) thPn. h ~.tcd ~7-1('er reflux for 2'r.Jurs.1'he r:,ixture was cooled, evaporated and azeotroped with toluene (3 x 200rn1).
The res)duc wa.s dissolved i.n :20 io aqueous acetic acid and stirred for 2 hours. The mixture was evaporated and azeuaoped with toluene (4 x 200m1) to afford the subtitle compound (1t,.ig).
2o 1V~i.4 174 (M-t-I.-1", 100%) b) o-d-niti=c,-2-(l~ycap~'lti~io)-pyri_uij.:i, -;--ylj aminol-telii'~.i? ~ 4~ x' U-.G,Z-a:ir.~ tn j 1wl~Ca ~~~ ~IJjb4 yl - i,:i. l1ioX131-~-~ C
A solution or the product from step (a) (10.0g) and N,.N diisopropylethyianune (35m1) in 25 TH~ fs' )(tznl N vras stire-j' for :hot r. ''' ie rrtixt:re was :".,.i.ter,.-d and the sc),utior was added over ihonr to a solution of 4,6-dichloro-5-nitro-2-(propylthio)-pyrimidine (prepared as descr;be4 in WO 9701084) (25.57g) in THF (1000rn1) and stirred for a. f'urtber 2hour. The solvent voltime was reducUd in vacuo and ethyl acetate was added (1000m1). The mixture wa,.; wa.shed with war r ancl the orq?nic layers were dried (MgSO4), evaporatf-e and 30 purtaeci i;SiOz, iso:h.e.Yar.e-ethyl ar,etqte as eluant) to afiord the sub-title comonun.d (=1L='~''_', MS 40 ? 00%) WO 99/0:. 143 PCT/SE98/01393 c) [3a.R-(3aa,4a,6a,6aa)]-6-[[5-Amino-6-chloro-2-propylthiopyrimidin-4-yl]aminoJ-tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-d ioxol-4-ol The subtitle compouj:id was prepared according to the method of example 12, step (b) using the product of step (b).
MS (A.'PCI) 375 (M+H+, 100%) d) [3aR-(3aa,4a,6a,6aa)J-6-[7-Chloro-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]-pyrimidin-3-ylJ-tetra hydro-2,2-dimethyl-4H-cyclo penta-1,3-dioxol-4-01 The suetitle compouna was prepared according to ttie rriethod of exampie 12, sLep (c) using ia the product of step (c).
MS (Al'Cl) 386 (M+}i+, 100%) e) ('i.t: ..ra?rs)-2-(3-Me.hoxyphenyl)cyclopropanamine hydrochloride The subtitle compound was prepared according to the method of example 19, step (i) using (lh-trans)-2-(3-methoxyphenyl)-cyclopropanEcarboxylic acid(Prepareci as described by Va1,g?ar(-,a eta!. T. Cheni. 's'oc.,. Perkin '1'rans.. 1, 1994, 461-70). The product was taken up in 2N HCi ard freeze dried to afford the hydrochloricle sa!.t.
MS (Ai:'i.':!) 164 (iV1+H').

f) [LS'-[3a,2P,3P;4!x(3 S*, 2.R*)JJ-4-[7-[[2-(3-1Vlethoxyphenyl)cyclopropyl]amino]-5-(propygtttio)-3H-1,2,3-triazaio (4,5-ef) pyrimiriin-3-yl)-cyclopentane-1,2,3-triol To a suspension of the eroduct ,~rom sten (d) (0.40g) and. s*.ep (e) (0.28g) in dichio.*omethanP (20m1) was adderl N, rV=diisorropytethylam:,ne (0.89mi!, the resulting . . , .
sollli,UCi wi:..S ttit~r.i st;.rrec;. at~ raom tc~rr:reratuYc; fo~,1 huurs.
The reaction ulixI,.;r! was concentrate;o and tiie residue taken up in iiiett,ariol (45rn1)/2N HCl (5m1), this solution was then at. .ra.l, a room tr,mpc:atu;re for 16 hours. The reaction mixture was concentrated and the residue partitionea between water (50m1) and dichloromethane (50m1), the organics we3 e 1-1e.3 (MgS.:)1l-), i3':terctd, and con(xntrated. '['be product was purif'ie:c; (lil'LC, Novdlti~;kl' c~:18 colurr,n, (r.1 ,/o aqueous ainmonium aceta.te:acetonitrile, a0:50) to afford the M1"; 1:.;].) 47 :j (1Vlr~t 1C) 13%) Nivtt: o11(dF-a~tVi~~Ci j9.3) (it-f., d, J=,',.tl hz). "i.23-ti 81(411, m), 5.1'i-4.:+i (4H, m), 4.74-4.' ~- (1f-l, tn), 4.00 (."di, br s), 3.84 (IH, br s), 3.79 (31i[, br s), 3.29-3.26 (1H, m), 3.06-2.87 (2ii, m), 2.69-2.61 (lfi, ra),1.19-2.14 (1H, m), 2.00-1.94 (1H, m), 1.76-1.51 (3H, m), 1.4:,.- 1. 29 ('Ji, -n), 0.87 and 1.05 (3H, t. .1=7.6 k-Iz).

WO 99/051.43 PCT/SE98/01393 Examlrit 25 [1 r'- [1 ~~?[i,3(3,4a(1S~, 2R*)]]-4-[7-[[2-(3-Methylphenyl)cyclopropyl]aimino]-5-(propyl~tihi.a)-3H==1,2,3-traazolo [4,5-c1] pyrimidin-3-yI]-cyclopentane-i,2,3-trkol a) (1 R-frans)- 2;(3-Methylphenyl)cyclopropane carboxylic acid Prepared acec,rding to the method of Example 20, step a) using 1-ethenyl-3-methyl-benzene.
MS (APCI) 175 (M-H}', 100%) to b) (l~t-~raras)-2-(3-tdiethyipinenyl)c~~ topropanamaaie, ~X-(~t*,1~")]-2, ~n dihydroxybutanedioate (1:1) Prepared according to the method of Example 20, step b) using the product of step a).
NPvi~;. !4l(d6-D&1SU) 7. i'/ (1l-i, t), 6.98 ( i Fi, d), 6.93-6.89 (2H, m), 3.93 (2I3, i), 2.70-2.66 (1H, m), 2.2 J (3H, s), 2.13-1.08 (1H, m), 1.24-1.19 (iH, m), 1.19-1.09 (iH, m) ts c) [1S-! I oc,2(3,3p,4a(1S*, 2R*)]]-4-[7-[[2-(3-Methylphenyl)cyclopropyl]amino]-5-{pro.py"t'iio;~-:iH-1.2,~-tri,iTolo[4,5-d]pyrirnidin-3-~r1]-cyclopentane-~
2.34riol The ~itlr; ~c r:~poL7nd ~r: sir,~;pareJ. oc,=crrrf;ng to the nyQrhud of exampie ':4, step (f) using the products af step (t)) and exampie 24, step (d).
20 MS (.~.f C11457 (r:'!-I'1', l0E) 1o) NM'R 6ri (a5-DiViSGj 9.33 () H, s), 7.19-7.14 (1H, m). 7.04-6.96 (3H, m), 5.12-5.10 (1H, m), 5. i i3-4.9 i(1 ri, m), 4.94-4.92 ( i H, ni), 4.92-4.90 ( i H, m), 4.69-4.64 ( i ti, ni), 3.94-3.92 (1H, m., 3.78 (1H, s), 3.20-3.17 (iH, m), 2.97-2.85 (2H, m), 2.62-2.58 (1H, m), 2.29 (3H, s), (iH, m), i.97-i.83 (1H, m), 1.54-t.4i (2H, rri), 0.84-039 (311, t).
Ex.az-,1?,,.
2R*)]]-4-[7=.[~z.-(3-C'hlorophen,y1)cyclopropyl]aru:inol-5-lpt ,2r3..ti krsli:~fYj4,5-L )py I'iLClltilln..3. 4-evL'i'4bnentane-31.7,3 .":ItO

a) 13a.4-[1(E),3aa,6a97a5]]-1-[3-(3-Chlorophenyl)-i-oxo-2-propenyl]-hexahydro-8,8-ditlserb~ I_3 ~'-3a,6-nr c~tt~aa:v 2,1~ .benz isflthiazole=2,2-ciioxirie The sutrt.l.e compoun:-l,ws nrepzrPd according to the Tnethod of example 19, step (f) using 3-(~
NI:: (APt ;-o; 1.53 (100%) WO 99,105143 PCTlSF98/01393 b) a3:i F, ..[1(hS*,2i *>yJaa76a,7a~) j-i-[[:?..(.3-Chloropheny1)cyclopropyl]
carbonyl]-hexahydro-8,8-dimethyl-3H-3a,6-methano-2,l-benzisothiazole-2,2-dioxide The subtitle compound was preparee accordiiig to the method of example 19, step (g) using th: p: ccilzct of step (a).
M~: ") 3961394 (M-+-1~'"), 41 l. (100%) c) (11,'-=i.-ans)-7-i;:3.-Cihlorophenyl)-cyclopropane carboxylic acid The suf tiile compouncl was prepared according to the method' of example 19, step (h) using the pruduct of step (o).
MS (APC:1) i95i iyi (M-ri' ), 195 (1OU ro) d) [l.k-=traras]-2-(3-i::Yiloropbenyl)cyclopropylaminc:, [R-(R*,R*)1-2,3-dinydroxybutanedioate (!:1) The subtitle compound was prepared according to t:ie method of example 20, step (b) using the product of step (c;.
NM~ ~+ (J5-:aMSO) 1. s 1.23 (2"ri, rri), 2.10-2.20 (?k-i. m), 2.70-2.74 (?H, m1, 3.95 (2H, s), i .08-'i.32 (4h, m ) e) (1,'Z-[l a.2,~õ3(3;4a(1S*,2R*)]]-4-[7-[[2-(3-Chlorophenyl)cyclopropyl]amino]-5-zo (pmopvythio)-3R=1,,.:.3-trr2izolo[4,5-=dlpyrimidin-3-yl]-cyclopentane-1,2q3-triol The title compound was prepared according to the method of example 24, step (f) using the p,r.od~ crc ot step ,d) and ex.arnple 1,4, step (d).
MS (A)'(_'() 477/4"79 (,I"/f+JE.+), 477 (100%) NM'k<. (4;1, iri;, 5.(;:7-4.93 m), 4.68-4.65 3.94 (1H, br b.c .5'õ :3.20 1.H, ~r s;, 4 .9?-2. ;'y (211, :zi), 2.64-2.56 (1'"tI, y..;, 2.26-2.13 (1H, m;, 1.92-1.38 (IH, -.y), 1.70-1.40 (4:1, ni), 0.99 (3H, ,~, J--7.2 Hz), [18-I'lc+,,:1~3,"~,t,4a(1 S*, ].j -4-(-7-[12-13-Nitroprenyl)cycloprovrvlinoj-5-(p~=<~l~y:r:;:ia) 3!~ [4,S-ujpy6midin-3-y 11-cyclopentane-1,2,3-triol a) (1,f' ;:, arz. )-..-',3-'~itrophenyl)-cyclopropane carboxylic acid Preparea according to the method of exarnple 20, step (a) using 3-nitrostyrene.
MS ( A1'CI) 206 (nl-H ", 100%) WO 99,165143 PCTISE98/01393 b) (1R-truns)-2-(3-Nitrophenyl)cyclopropanamine [R-(R*,R*)]-2,3-dih~,drrirybutanedioate (1:1) Prepared according to the method of Example 20, step (b) using the product of step (a).
NN1R 8H!d6-DMS ) 8.06-7.98 (2H, m), 7.62-7.53 (2H, m), 4.00 (2H, s;, 2.84-2.77 (1H, rn). 2..41-2.34 (11-1, m), 1.41-32 (1H, m), 1.32-1.23 (1H, m).

c) [3aR-[3aa,4a,6a(iR*, 2S*),6aa]]-6-[7-[2-[(3-Nitrophenyl)cyclopropyl]amino]-(propl,lthio)-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yl]-tetrahydro-2,2-dimethyl-4H-cyclopentan-1,3-dioxul-4-o1 -o PrelZõred according to tr_e rr.Ã:tr.od of Example 1, step (a) using the product of step (b) and Exampie 24, step (b).

d) ri5'-i1a,2[3,3~,4a(1Si , 2R%)]]-4-[i-[[2-(3-iVitrophenyl)cyclopropyl]ar.liloj-5-(propylthio)-3H-1,2,3-tri;tzolo [4,5-d] pyrimidin-3-yl]-cyclopentane-1,2,3-triol -s Prepared accoraing to the method of r,xarriple i, step (o) using the proGact of step (c).
m.p.
MS 4M (M-!-iH ' , l W%) NN:#, orl (d6-13Ivr01-0) 9.43 (iH, e.), 8.08-6.01(ZH, ra), 7.'70-7.56 ( lE-I, m), 5.13-4.87 (4H, m), ,.6'-:-4.60 (IH, m), 3.97-3.76 (2H, m), 3.31-3 04 (1H, m), 2.93-2.17 (2H, r.-z) 2.54-2.51 20 (IH, m), 2.3F-2.28 (1.H, m.) 1.97-1.88 (2H, m.), 1.63-1.38 (3H, m), 0.76 (3H, t).

Exam~le 28 2k*)]]-4-[7-rt2-(4-P'henoxyp!hsnyMlR.yclopropyl2ain-iTiol-5-(pl'fr!I!'1'~.~;1=.iot-3~?=E..2,3-rk .;~zo9o[4,:i-d}l;yrtitrr~diu-3-yl]-cyclopenlaLzv-1,2,3-triol a) ()..6'-tr=a.,zs}-2-(4-F'henoxyphenyl)cyclopropane carboxylic acid Prepared accorrting to tne metnod of F;xarriple 20, step (a) using 1-etlienyl-4-piienoxy-bccz~:.,;.

b) i:.;1 ar ar ?-2 ( t Fl~r~.~o,.Yl~hexgYlit j r.loprc i~analtaiy-; e, [~;
.(1?' ~.*)i diity c' k ";X1' : atanec'.oatõ 1.1:1y Fr(.pse::a r.othe ;:,.E-tnc,d of 1/xample 20, step b) usir,g tne product of step a).
c) henoxilph.envl)cyclopropyl'amino]-5-3s (propyltbio~-3H~-iL,2,.3-triazolo[4,5-djpv,rimiclin=-3-3,1]-cyclopentane-1,*.~,,?-triol Pr-t;~arF,i a:=orciin:~; to :lie ;nethod of Example 2~ti, step (f) using the pro.iuct from step (b) and the product from Example 24, step (d).
MS (A.PCT), 534 (M+H+, 1Co0%) NMR 8H (d6-DMSO) 9.35 (1H, d), 7.41-7.35 (2H, m). 7.25-7.22 (2H, m), 7.14-7.09 (1H, 5 m), 6.99-6.94 (4j;i, m), 5.12-5.11(1 H, m), 5.04-5.01(1 H, m), 4.94-4.91 (~.H. m), 4.67-4.64 (1H, m), 3.94-3.92 (1H, m), 3.80 (1H, s), 3.20-3.17 (1H, m), 2.99-2.87 (2H, s), 2.62-2.57 (1H, m),'L.19-2.10 (1H, m), 1.99-1.90 (1H, m), 1.56-1.49 (2H, m), 1.32-1.30 (1H, m), 0.85 (3H, '~-=

io Example 29 [1S=[1cx,2(3,3P,4ct(iS*, 2l2*)]1-4-[7-[[2-(3-Phenoxyphenyl)cyclopropyl]amino] -(propylthio)-3.6f 1;1,3-tri;azolo[4,5-djpyrimidin-3-yl]-cyciopentane-1,2,3-triol a)1-1.,tixenyl-3-Phenoxy-benzene A s=i, pe,r:sion of trinhe=Iti-lFnet~ylnho~,phoniurri bromide (25.23g) and pot.assiurn tert-butoy,id (IM soiutior in *.etr.ahydrofuran) (75.67m1) was stirred at 0 C for 0.5h. A
so'uLI.C,n cr 3=phercxy-benzal.rlehyde (10.0g) in THF (10 ml) was added to the mixture and the r..a+:ron mixture st :rr~ ~i at 1!'C fci 4h. Arnmcni?:m chlorid:, solu'rion wus a&ed and the mixf,iextracted with methyl e-.her. 'Ahe organic extracts were com.bine~, wasned with water, dried and concentrated. Purification (SiO2, isohexane:ethyl acetate 4:1as eluant) gave thy subtitle co*npc,und (7.12g).
NMF SH (CL'C13) 7.78-7.65 (1H, m), 7.58-7.41 (1H, m), 7.36-7.26 (3H, m), 7.16-7.06 (2ti., (2h,;7z.), 6.92-6.3~ (11~, rti), 6.72-6.62 (1h, m), 535 (141, ti), 5.27 (1H, m ~.

b) (1~-'-n.r~al-2-;3-Phen~r.xyl~~,cL:y1)r~;~:woprcF~ aane carbox,=lrc acid Prepared according to the method of Exampie 20, step a) using ihe procit:cc froi~i step (a).
1VC;i ( ~~-'CTZ 253 (M-H'" ll)U%) c) (l.~t-tran.s)-2--(3-phe~?,xyln-her,),l)cvrlopropadnami-le~, dtnynroxyb7,tanedl.oane "'d.,ii) Pr~,~,l*P,: z,.,ordinp to the meth.od of Example 20, s*ep b) using the pr.oduct of step b).
I~N I Z sill (d 1? :1';, -J) 7.4: (2 F1 tn), 7.3 ?.7.2 5 (191, r.,i), 7. i6-7.?.1 ; iI=T 7.00-6.96 6.'3 t-6; 1". i1~1, .4 94 (Z H, s}, 2 -2.66 rn) 2.14-2.11 (1H, rn ', 1.26-1.10 (1 H, m), 1.15-1.11 (1 iEi, m).

*rB

WO 99105143 i'C'.'/5E98/01393 d) [1S-[1cu,2[3,3(3,4a(1S'*, 2R*)]]-4-[ -[[2-(3-1PhenoxyphenyI)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yi]-cyclopentane-1,2,3-triol Prepared according to ' he method of Example 24, step (f) using the product from step (c) and ibe ~Produc4 fr,r:~. Example 2,4, step (d).
MS (A.'PCI) 534 (M+I-I+, 100%) NMR SH (d6-DMSO) 9.35 (IH, d), 7.41-7.36 (2H, m), 7.32-7.27(1H, t), 7.15-7.10 (1H, m), 7.01-6.95 (3H, m), 6.90 (1H, m), 6.82-6.79 (1H, m), 5.12-5.10 (1H, m), 5.03-5.01 (1H, m), 4.93-4.91 (211, m), 4.68-4.64 (1H, m), 3.94-3.92 (I.H, m), 3.78 (1H, s), 3.20 (1H, m), 2.97-2.8.5 (211, m), 2.6i-2.57 (il-i, m), 2.18-2.13 (1H, m), 1.96-1.92 (iH, in) 1.i5-1.4'/ (2H, m), 1.35-1.31 (1*fJ, m), 0.83 (3l-i, t).

Exana.raie 30 [l:~ u,2p,3(3,4a(1 S*, 2R*)]-4-[7-[[2-(3-Aminophenyl)cyclopropyt]a:,nitaoj ~
=S=-(p ro pylthio)-3H-1,2,3-triazolo [4,5-d] pyrimislin-3-yl]-cyclop entane-1,2,3-triol A sUSne:nSier, o* S% pailadi,.im. on cha-coaY (40rng) and the producr from example 27, step (d) ( t, )4.r-,g) in ethanc: l (1 t)znl) was stir-red under two atmospheres nressure of hydrogen for rioi.ir4,. 'i ne rrtixrure wAs t7ltfre,i and purified (Si02, isohexane:acetone, 1:1 as eluent) to giva *bc title c;om-noaxr..d (7 i rng).
20 m.o.ir.,:~-7 C' M.S ;A?C:{) 458 (M+Hi, NM'E: 6H (a f-D.MSOj 9.2'r ~ l h, ai, 6.91 (1H, *.), 6.39-6.29 (314, m), 5.16-5.0'1 (1 H, m), 5.06-4.~?8 (SH, m), 4.70-4.59 (1H, m), 3.95-3.90 (1H, m), 3.84-3.75 (1H, m), 3.21-2.83 (311, aS -2.53 (i.li, m', ~.01-1.Si (2}1, ra), 1(4H, rn; G.i;':Jffi, .).
Ex~>cupie 31 [1~S'-~"~.:x,:jo.;?~, i~i)] 3-,;'-{;3utylam:.t:o) -{propyltlnio}-3,F~ 1,2,3-tri.azolo[4,5-alic~; r r .nir';r-3-y3]-5-("3-:,~ :lr~~~yp.-cp~r_~)-cyclopst~tane-1,2 diol.

a) IWr#3utyl-(2,4-dimethoxyphenyl)methanamine Th~ s~*6krle .:-ornpounO. war nrepvreAd accordi.ng to bp rnethod cf exampie .(Z, s.ep (d) Us?I'.r; 7.wtV~F1.",'?IPP, M/ R ST-? ;ICL7tv13) 0.90 (311, t, J=7.2 Hz), 1.33 (2H, sextet, J=7.2 Hz), 1.48 (2H, m), 2.57 (2:ti, nil)õ 3.71 (2H .*n), 3.30 (3H, s), 3.81 (3H, s), 6.41-6.46 (2H, m), 7.12 (1H, d, J=8.1 ft~ ).

b) (1S-cis)-4-[7-[N-Butyl-[(2,4-dimethoxyphenyl)methyl]amino]-5-(propylthio)-1,2,3-triazolo[4,5-r1]pyrYmidin-3-yl]-2-cyclopentene-l-ol The suUtitle compound was prepared according to the method of example 12, step (e) using the products of step (a) and example 12, step c).
MS (APCI) 499 AM+II+,100%) c) [3a.1R-(3aa,4a,6a,6aa)]-6-[7-[1V Butyl-[(2,4-dimethoxyphenyl)methyl]amino]-(propylthio)-3H-1,2.;3-triazolo [4,5-d] pyrimidin-3.-yl]-tetrahyd.ro-2,2-d.
imethyl-4H-cyclopenta- l,3-uioxoi-4-a4 io TnE subtitie cornpourid was prepared according to the method of example 15, step (c) using the procuct of step ;b).
MS (APCI) 573 (ivi+H"., 100%) d) [3aS-=(3aa,4a,6(x,6aa)1-1V=Butyl-lW-[2,4-(dimethoxyphenyl)methyl]-3-[[[(tetrahydro-is 2B.-pyran-2-yl)oxy]propyljoxyj-2,2-dimEthyl-4lt'-cyclopenta-I,3-dioxoi-4-yi] -5-(prQ1R=y) t1h.ro)-:3.q- 1,1,_;-tr,azoloj4.5-d-;)yrxmid in-'/-amine.
Tr_e suhntie :;cmround was prepored according to the method of example 13, step (a) using the prorI+J.Ct of srFp (C) sIld ?-(3-brom.opropo;:~.)-2H-r.etrahydrop,,ran, ea cept Yhat the rea.ction was aliowed to proceed. foT 18 hours at reflux temperature.
20 MS (.A.Pra ) 715 e) ta,:3ji,5~i)1 -,~-~'1-(Butylarnino)-5=(Fromylthiul-3~1-1,2,3-tri~zclo[~t,5-djp:vx imadin-3-vl j-5-(.i-G;laJ roxF pror- oxy)-cy clopeni:ane-l,l-dio1.
ThF :.i 1(; cv-rY:pou~d ~V ".s pr'e:pared accr,;=ding to tlie methoc. of e:carrrole 2, ste;}) ;oj using the 25 pror3 Ac+ -..

NM'r'; i;rl (ci6-f3MS(J) J.9:. (.IH, ~, J=7.5 Hz), 0.99 (:il-i, t, J=7.5 Hz), 1.34 (2H, sextet, J=').2 :i4'*z), 1.38-1.74 (6H, in), 2.02 (1H, m), 2.62 (1H, m), 3.08 (2H, m), 3.44=?.56 (6H, m), 3.70 (1H m), 3.91 (111, m). 4.40 11 I-:, t, J: :5.1 Hz), 4.54-4.59 (1Ny m), 4.95 (1 H, q, (Is-I, d. J=-3 ') -Hz), 5.~i~ (11=t, ~., J=-5."s ~z), 8.-)7 aTu; &.6:. ( tl-i, t, .1=5.4 Hz).

WO 9105143 F'CT1Sk.98/01393 Example 32 [1S-j 1 ec,2a,3 (3,5(3(1 S*,2R*)]]-3-(2-Hydroxyethoxy)-5-[7-[(2-pheny' cyclopropwl)amino1 -5- (prop, vlth io)-3H-1,2,,3=-triazolo [4,5-d] p,=r imidin-3-yl]-cycCopentane-1,2-diol.
a)1'V-[2,4-(Dirnethoxyphenyl)methyl]-N-(2-phenylcyclopropyl)-3-[[3aS-[3aa,4a(1S ;2R*),6a,6aa)]-[[[(tetrahydro-2H-pyran-2-yl)oxy]ethyl]oxy]-2,2-dimethyl-4H-cyciopenta-1,3-dioxol-4-y1]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-7-amine.
to The suotitie compound was prepare,i axording to tr,e rnethod ut exalril;lF;
31, step (d) using the product of exampie 23, step (a) and 2-(2-bromoethoxy)-2H-tetrahydropyran (prepared ac;,u~aing zo the method of K. F. Bernady etal. J. Org. Chem. , 1979, 44, i4:;.8.) MS (r1E'la) i61 (iVl+F-i',i00'ro) b) [lti+-[la "a,3(~,5~(1S*,Z1{*)j]-3-{'Z-~ydroxyethoxyj-5-['7-[{Z-phen-licyclopropyl)amirt-]-5-(pr-op-7lthio)-3+l'I-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclemE"t ene-1,2-.clioa.
The title c.ompound was prepared acco.ding to the metiiod ot exampie 2, step (b) using the product of step (a).
M-'~! "Ai't_), 487 (lvl+klX)0~I~) NMR 6H (+JVSO-db) 9.36 (1H, d, 4.0Hz), 7.31-7.27 (2H, m), 7.20-7.16 (3H, m), 5.13 (1 H. d. ,'=F.41-!z), 5.06 (1 H,d, J=4.OHz), 4.97 (1 H, q J=9.2Hz ), 4 63-4.55 (2H, m), 3.94 (11-:, i;r), ,;."; 5(1H, m), 3.52-3.47 (4fi, m), 3.21 (IH, m), 2.96-2.93 (1H, m), 2.85-2.82 (1H, m),1.5~-~.?U ;ii-i, rn), ::.13 (::Fi, m), 2.03 (lt:, in), 1.54-1.4L6 (3ri, m), 1.36-1.31 (1H, m), Wsi. ( :t-Id-Exs mY)l:'. 73 [1-i" I: J. ~l,i.~,.Y ~~,J~~_~i~ k.y~i.~. -3..( ~q Vllroxyn7l!~th~' l)-,-[7-[
2-(4-3o mctuexg,pl:er.S~i)cy~;lepro~'yljain'_i_nJa] ..S'-(propyif:isio)-3h=1,:2,3--triazalo[=1,5-dJpyrimidin-3-.y~

a) ~:~~~?-f3a!x,4a,6r(l R*,:Sx),6aa]-'1'etrahydro-ti-[7-([2-(4-merh.: yp5;~r+.y;i)t,3rg:~iar ~~~-.,y~~~.z~~Yx~z~i-5= =c"l:yrimidin-3-.I,i.}-.2,,2-di-methyl-4 K-eyeiopenr:a-1,3-dioxo[e-4-m~thanol WO 49.'06143 PCT1SE98/01393 Prepared according to the raethod of Example 1, step a) using the product of Example 20, step (b).
MS (APCI) 527 (M+W, 100%).

b) "? ~-(1r,2a,3p.,5p("1S*,2R*)]]-3-(Hydroxymethyl)-5-[7-[[2-(4-me+=iri, ~ypifaearyl)cyclopropyl] amino]-5-(prr~ylthio)-3H-1,2,3-triazolo [4,5-d]pyrimidin-3-yl]..(.yclop,eniaue-i,2-ciiol Prepared according to the method of Exampl 1, step b) using'the proauct of step a).
M'y 1,R.?CI) 4b7 (iv1+'tl', C'_J0%) to Nivklw:,&"tI (d6-DMSO) 9.28 (1H, d), 7.14 (4H, d), 6.85 (2H, d), 5.00-4.95 (2H, m), 4.75-4.68 (2H, rn), 4.47-4.40 (It-i, m), 3.88 (1H, q), 3.73 (3H, s), 3.50-3.40 (2H, m), 3.13-2.80 (3H, m), 2. 27-2.02 (3H, n1), 1.90-1.77 ( I H, m), 1.60-1.40 (3H, )m?, 1.28.=
1.20 (1H, m), 0.85 (:>I3, 1).

Example 34 [11?-(1 a,2a,3lb(1.R4,xS*),5b)]-i-(7-[ [(-i4-~;;liloroQjaenyl)cyclo~propyt)pamino j-5-(pr~)rjyithzo)-3H=1,2,3-triazoio [4,5-d] pyrimidin-3-yl]-5-(hydrox,ymethyl)-cyclopentane-1,:?.drol 2o a,a[:#aK [{ac.;4a,!,r(~ ~*,2.~'*),6a~]-~ [7.-f[2-(4-l:'htoroptrea.yf)r.lc.lopropyl]anaino]-5-(prsrPvtthin?-W-1,2,.3-triazo).of4.54Jpyrimidin-3-yl]-tetrahydro-2,2-dimet#~.,yl-4H-c,yc.y,,)f+enta-l,3-dioxAp-,' *nethanol Prenared accor~s.n.g to th.e rnethod. of Fxarap!,~ 1, ster a) using the product of Example 22, stez~ il) ano !.+-d:.cx.ane Gs s,)Iverlt.
53 t(M+N', PJ09,)) h rvfi~. ~,J{ (C-_XI:3) 7.3?. -7. 13 (4H, m), 5.28-5.15 (2H, m), 4.72-4.69 (1 H, m), 3.82-3.65 3.06-3.01 (211, m1, 2.62--2.45 (2H, m.), 2.45-2.28 (l.H, rn), 2.21-2.07 (l.H, m), 2.01-2.1;'~ 1.~'8- .60 (l +:f, rn), 1.53 i":;fl, rn), 1.33 (:3Yi, s),_ 0.94 (3H, t) 3o b) [ ~..~ =~i.~:~a,3i~(i1:R,c.~ ),5b]]-3-[7-[[(2-(4-Chlorophenyl)cyclopropyl))amino]-5-l's~r o}~~ttl~i~ }~~ fi'- ~~,3 tri:rz~~xo i t5-~~h~"'at~if~n:~-.'~==yl~ ~~-( ~~~ E~rti:u cr.,~~ ar~t,ts3,ae-14-di0"9 PrR: ,:are I according to the rriethod of Example 1, step b), using the product of step b).
MS (F~1%;:1) 491 ~M+H+, 100%) lNMR3141 11-t:, ci). 7.35-7.2i 4.4, :id'), 5.00-4.9 ,2fi, ;:n). z~~.'i =~-4.70 (2H, nn), 1.4:3-4 ,r0 "q, in), 3.88-3 8 i(', H, m:), 3.4,5 (2I-I, r.), 3.N.5-3.05 (1H, c~-0, 3.00-2.80 (2H, WO 99'FJ5k4,; PCT/SE98/01393 (1H, .n), 2.17- 2.00 (211, m), 1.90-.1AG (;.H, 171), 1.60-1.46 (41i, m), 1.40-130 (1H, m), 0.82 (3H, t).

Ex,ananle :TS
5 [1.R-1 w cx.:lcx. 3p(l;i*,2F" 1),5pj]-y-[7-[[2-(3-Chlorophenyl)cyclopropyl]amino}-5-(propylthio)-3bT 1,2,3-tria.zol!)(4,5-djpyrimidin-3-ylJ-5-(hydroxymethyl)-cyclopentane-1,2,.3iol a)E3a.Ps-[3aa.,4a,6a(Yll",zy'"),6aaJ-6-f7-[[2-(3-Chlorophenyl)cyr,loprolryljamino]-5-io (propylthio)-3H-Y,'L,3-triazolo[4,5-d]pyrimidin-3-yl]-tetrahydro-2,2-dimethyl-4H-cycl cpenta-".,3-cYioxole-4-methanol PreparA according to the :neth.od of Example 1, stez-: a) using tr.(..
pracl'!.r,~t of E:.ample 26, step 1 ,)a:-i 1,4-aroxane us solvenc.
MS (~PC1) 331 (M+LT, lut)%).

b) ji".R (1S*2dt*),53]]-3-['?-[[2-(3-C'hloMcphenyl) cycloja;ropyllaroaneJ-5-(p,-op:i1,'ia;o4.-:3lH,-?,,2,'-4-triazolo [4,5-d] ipyrimidin-3-yl j=-S-(hydrGa.ymeth.yi)-cyc.iopentane-1,2-droi Prepare:d according to the memod of Example 1, step b) using the product of step a).
20 Ml;~ !:~~Cl) ~"r', Nivak. tsti (d~-1~~NdtiCo) 9.34, (1H, d.), 7.28-7.10 (4H, m), 5,05-4.93 (2H, m), 4.78-4.71 (2H, m), 4.48-4.40 (IH, m), 3.86-3.80 (1H, m), 4.50-4.40 (2H, m), 3.24-3. ]. 8(1 H, m), 3.00-2.80 (2H, ni), 2.34-2.21 (1 H, m), 2.20-2.00 (2H, m), 1.90-1.80 (1H, m), 1.60-1.38 (4H, m), OF}~:;11.~' Examu'1e:36 [1~ r~ rt,2o:, Y f~,5~~~:15*~Z~*)tt ?-{Me 6axamettnyl)-~+-['7-[(2-pbP~r~
Xr.vr.l~pr ~p~~)aminoJ-5 '.~.~ ~ . 1.

a) [3ati'-[3aa,4a,6a(1.R*,2,5*),6aaJ-6-(7-[(2,4-Aimethox,yphenyl)tnethyl-(2-pr~3e~~rt,,'{~,A~lil'U~yj/~)d~,~11i10 :i ~r~9tU][~~lt~

tetrabyrlr)-:41-elimethyl-4H-qclopF.nfa-lz3-dioxole-4-rsethanol Pi -.cor3i.ng to the method of Example 1, step a) using the product of Example 12, Ste-r, M

b) [3aS-j3aa,4a(1S*- 2R*),fia,6aa]]-1V [(2,4-Dimethoxyphenyl)methyl]-3-[6-(methoxymethyl)-2,2-dimethyl-tetrahydro-4S-cyc.lopenta-1,;l-dioxolan-4-yl]-N-(2-pherylcyclopropyl)-5-(p ropylthio)-3H-1,2,3-triazolo [4,5-d] pyrimidr ne-?-amine Sodium hydride (:i 1mg, 60% in oil) was added to a solution of the product from step (a) (0.26I;'; and rnetl~j,l iodide (1).15ml; ix,KIN-dimrthylfor-rnamide (1.5rYii) aaTid ::l-,e resultant mixture was stirred for 2 hours. Water was added and the mixture was extracted with ethyl acetate 3nd the extracts washed with water, dried, concentrated and purified (Si02, ethyl ischexane:acetone, 4:1 as eluant) to afford the subtitie compound (C.12g).
MS (HPl::-) 66i c) jli-+.ta,zu,3N,S~(ilS;,lA*)11-s-(NTethoxymethyi)-5-j7-[(2-phenylcyclopropyr)aLnin o)-5-(propylthio)-3i':1=1,'l,3-triazoio [4,5-dr pyrimidin-3-yl]-cy;..x di.j ifti~.ne-1,l-diol Prepar;;d according to the nZethod of Example 2, step b) using tne product of step b).
M.P. i41-150"C.
M.~ fA'F(--T) 471 04-+H+. llHo%).
NNIR E~.-i ;dfi-UD:4S(?) 9.33 (1 1E-T, cl), 7.20 (5H, rn), 5.02 (1H, rn), 4.SI
(I1-I. rn), 4.41 (1H, m), 3.85 (1 H m), 3.40 (2H. m), 3.28 (3H, m), 3.20 (1HT m), 2.90 (2H, m), 2.25 (2H, m), 2.11 (1 .H, rr?, ?..86 (i.F), m;. 1.52 (?.H., m.), ".49-i.32 (2H, m). 0.83 (31:, t. J-- 7Hz).
Exan-pl~ 3't [1.'-! ;t oc.2cr.,3~,5(3(1S*,2.t2*)] ]-3-(Hyd roxym.eth,yl)-5-(5-(methyitliio)-7-M (2-phi-raylcyc).opropyi)aminol-3N-1,2,3==triazolo [4õ5==cP] pyrimidin=3-vl]-eyclopentane-1,2-dioi a) phr~~.a';,y~aa,~~r'a~p~~l;:3a~~ir~oj-5-lprop~.=t~: ~a~idin-3-yl]-.

Pr.7at,-.c, a.c=cc-.'ini7 ro 'i:hP z:,L :had of T-"Xa.rr I?';: Stt-I (3,) uS}.J ; ; r.~d~z,~t of :Example 1, Ste*' M-~', i1'ii.''....i.~ L,=:~-~ tiv44i.J~~-{, ~1~t,)'ilOl b) [~S=-[loc.,2oc,3p,5[i(1S*,2R*)]]-3-(Hydroxymethyl)-5-[5-(methylthio)-7-[(2-phenytcyc-cpropyl)amino]-3H-1,2,3-triazolo[4,5-d'Jpyrimidin-3-yl]-cyclapentane-l,2-dial Prepared according to the method of Example 17, step (b) using the product of step (a).
MS (APCI) 429 f M+H+, 100%) NMR SH (d6-DIv9-SO) 9.33 (1 H, d), 7.3 i-7.1 5 (5H, m), 5.03-4.91(2H , m), 4.74-4.71 (2H, m), 4.4 ;-4.4i3 (114, m), 3.91-3.878 (1H, m), 3.51-3.46 (2H, m), 3.19-3.18 (1H, m), 2.33 (3I-I. s), 2.29-2.24 (1 H, m), 2.14-2.10 (2H, m), 1.92-1.80 ( l I-i, m l, 1.51-1.47 (IH,m), 1.35-1.32 (lYi, ni).
Example 38 [1.S-[la,2a,3p,5(3(IS*,2X*)]]-3-(Hydroxymethyl)-5-[7-[(Z-ptienyleyclopropyl)amino]-5-; (I==nt r,-; iiylethyi)thio]-3I'i=1,2,3-triazolo[4,5-dj ipyrimidin-3-,v1]-cyclo,-er.fi:ane-1,2-diol The vAti~: compound was prepared according to the method of Example 4, step b) using the proc t ct of Fxarr p]e 3%, step ?) anc'. l-methylet.han.ethiol.
MS (Al'C1) 4.57 (VI-44+, 100%) NN1R 611 (d6-DMSO) 9.35 (IH, s), 7.26-7.19 (5H, m), 5.00-4.97 (2H, m), 4.72 (2H, s), 4.4a (iH., s), 3.87 (1H, a), 3.60-3.64 (1H, m), 3.47 (2H, s), 3.17 (IH, s), 2.23-2.27 (1H, m), 2.09 (2y, s), 1.83. 1.85 (1:H, a1), 1.53-1.55 (1H, rii), i.23-1.36 (IH, m), 1.15 (3H, d), 1.09 (3:.', d ", Ex:inlj)ic 31) ciopropyl)amino]-5-0 r+.) ~,-z-rayltlria}-1xt-a, :;=-triazoio[4,:"s-rljpyrirc,ieLln-3.,y t].
;ym:lop ea taii,1,2..diol a) ;J-3.~l.y~iroxymethy!)-5-[7..[(2..
pEi,,~r*wt~ya Io-~.r,3p,yl) atnin a1-: -(prop-2-enylthio?.- 3.H-1.,2,3-triaz,ilo [4,5-dipv*'imidin-3-yl )-cyciopentane-1,.2-diol T~.(t s'fs, t orttooarid. was prepared. accordin.g to the raiFthod ofEx.amplh~
J, wtep (b) using the pr%): w.t o' :xarao]P ?',', ~tep (a) ar.d 2-;.rope:rae-l-tttiot.
M, ". ~"A":' cJ. y MV.+Y-T' , 1011 MbY.9. ll~Lll (C.h-DNP.: i(J) 9.001 7.36-7.16, (SN:, *x,.), 5.9y-5.80, !1';.{., r.r..;, 5.22 (iH, d), (2H, m), 4.67 (1H., d), 4.47-4.38 (3I-I, m), 3.91 (IH.. q), ''.75-3.55 (2H, m), 3.55-3.fi' (2. ~:, F..),1, 3ll l,!l (:~I , rn), 1,93 l.~ati t' 1l, :ut, 1.50...45 ,"' 1:~, ~Y:~), 1.34-! .?8 (1H, m).

Exailxiple 40 [lS, -[1 ot,2c,3p,50(1S*,'R*)]]-3-(Hydro-xymethyl)-5-j5-(4-methylphenylthin)=-7-[(2-phec{ylcyclLpropyl)auiino]-3H-1,2,3-triazolo[4,5-dJpyrimidin-3-yl]-cyclopentane-l,2-dicl Pre:pav.:cl accordirà to the rnethod of Example 4, step (b) using the product of Example 37, step (a) and p--thiccr: sU1.
MS (t'~1'Cl) 505 (M.+'rl+, 1,30%) Nivitc 5ii (db-Dl~/iSO) 9.23 (11-1, d), 7.48-7.44 (2H, m), 7.32-7.11 (711, rri), 4.94-4.88 (2H, to m),. 4.64-4.60 (21ri, m), 4.32-4.27 C111, m), 3.30-3.20 (2H, ni), ;li-i, r.a), 2.34 (3H, s), 2.22-2.15 (2h, rri), 2.02-1.98 (1H, m), 1.70-1.60 ( l H, m), 1.42-1.38(1 ri,.n), 1.20 -1.15 (irl, rn).

Exaninle 41 [1'&-[Yo.,za,3[3,5[3(l.i'*,2R*)])-3-(Hydroxymethyl)-5-[7-[[2-(4-metlrvlr)he .ryl)c.yciopropyl]arminoJ-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl] cyclopertane-1,'?-s!'ev a) 1 3aR-[3aa,4a,6a(illt*,2S'*),6aa]-Tetrahydro-2,2-dimethyl-6-[7-[[2-(4-methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-ytl-4.~./-cyclf)pe.uta-1;3-,rlioxnle-4-methanol Prr-par d accord:V,2, to rhe method of E;cample 1, stetD a) using the product of Example 21, stc~) bl,azci 1,4 dioxa~e as :olvent.

b) ~i,5[l(1.5'' ,2RY )]]-3-!Hy~draxYmetlryl)-5-[~t.[[2..~4-n. :hylphenyl)cyclopropy 1 J amino]-5-(propylthio)-3R=1,2,3-tria.zolo l4,5-d]pyrimidin-3-ytl = WF, cl+)pentane-l,d'.-diot acc:;: u:rl;; tci the ..~:,:nod ai '.ExampYe 1, ste a b) using tlle pr:;duct of step a).
9.30';11-1, d). 7 0A (4H, s) 5.03-4.92 (2H, rr,), ,!..7i (2H, s). 4.42-4.36 3t-~a 'x.i, s,, : 51,j-3.4i (2H, rrl), 3.2J.-3.10 ;1H, rn), 3.00-2.60 (2H, rn), 2.27 (3H, s), 2.25-2.20 (11i, m), 2.1:i-2.05 (21K, m;, 1.89-1.81 (1rI, m), 1.60-1.40 (3H, ni), 1.28 (1H, dd', (04 (.3ri, t).

W C) 99/05 t 43 PCT/SE98/01393 Exalr.l'fe 42 [1S-(1oy,2cx,:3(3,(R*),5P(lS*,2R*)] ]-3-(1-~Hydroxyctiiyl)-5-[7-1('2-phenylryclopropyl)amino]-5-(propylthio)-31"-d-1,2,3-triazolor4,5.=alpyrimidin-3 yl]-cy,cl o peatane-1,2-dio [
SJdiurra borohydride 11'0.50g) was added to a solution of the product of example 8(2.lOg) in metharol (100m1). The mixture was stirred for 1 hour then poured into water (300m1).
The nii,:ture was extracted wiih diethyl ether, washed with water, ctrie,d and ccncentrated.
Puriiication (HPLC, Chiralpak AD, isohexane:ethanol, 8:2 as eiuarit) afforded the title to eorn.poufia (0.16g). Secondary alcohol stereochertustry aetermirced by the method of B
Trost etal J. Org. Criem., 1986, 51, 2370.
MS (,kPC:1) 471 (1VI-%uh+. 100%) Nld/,i: ;'ltl (d6-DMSO) 9.31 (1H, d), 7.31-7.15 (5H, m), 4.91 (2H, m), 4.62 (:H, ca), 4.57 (1H, d), 4.3"7 (1H, m), 3.84 (1H, m), 3.74 (lIk, m), 3.18 (1H, m), 2.96-2.81 (2H, m), 2.11 is (3rf, rn), 1.96 ( il-l, m), 1.54 (:SH, m), 1.35 (1H, m), i.01 (3H, d), 0.79 (311, t).

Example ai-1 [l~~'-? ~.;x;2a.~~3;.r.: k),S~ifl,~ *,2R*)1)-3-(i..1Hyd~r~xye*.f;y~--S-~'1-i '?-pheravlcveloprirpyl)aminol-5-(propyYthio)-3 "H-1,2,3-triazolo[4,5-rY]pyrimidin-3-yl]-2o cycicspentane-Y,Z-dior Pr pared =r.ccorr_ing tl- the method of Example 42, further elution (H)?'LC.
Chiralpak AD, isoilex.tne:er:hanot, 8=2) af.'ordPd the title compound (0.18g). Seronaary a)cohol ste-e deter:rnire ? by the method of B Trost. etal J. Or?. Chem., 1986, 51, 2370.
25 bf':i:-rt_a)~~i~
Ni..:, 6r.E d), 7.16 (:ifi, zn),,i.95 ,211, t,Z;, 4.63 t:11, iY1), 4.62 (.i.;.i, Y.:>(l1-i, ni. ;, 4.02 (111, m), 3.62 (1H, m), 3.21 (1H, m), 2.96-2.82 (2H, m), 2.13 (: -.; _..89 (2H, m), 1.48 (3I-i, m), 1.33 (1H, m), 1.15 (3H, e), 0.82 (311, t). -WQ 991051143 PC7i/SE98101393 Exa,wplie 44 [1.R-[1 a,2oc,3(3(L'Z*,2S*),5(3 ) ]-3-[5-(Ethylthio)-7-[ [2-phenylcyclopropyl]
amino]-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yl]-5-(hydroxymethyl)-cyciopentane-1,2-dio l s a? [3z R-[3act,4aõ6a(1R*,2S*),6aa]-6-[5-(Ethylthio)-7-[[2-phenyleyclcTMrrp,!llamino]-3H-1,2,,3-triazolo[4,5-d]pyrimidin-3-yl]-tetk .thydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxole-4-m ethaanol Prz_?ara-:i accordiiig to the Tned.iod of E,:anple 4, stela (b) using ~.Je product of Example 37, stel -, t,,-,? anct,:;thanetrio1.
10 NlIS 1 48" (?Vl-rri+, iC0,3o) b) [1R-[1tx,2oc,3P (1R*,2S*),5(3]]-3-[5-(Ethylthio)-7-[[2-phenylcyciopropylI
amino]-3,H-1;Z,3-z. idzok,[4,3-d)pyrimidin-3-yl]-5-(hyciroxymethy-)-cyc-apeniane-i;2-+:iui Prepared accoraing to tnF; inetnod of Exampie i, step (o) using tine product ot scep (a).
15 1viJ (AYC i) 443 IjYi-t:;-r*, 100%) Nlv:k &.-10 5-L)ivi"20) 9.34 ~ i i i, a), 73 i= 7.15 (.ih, )cn), 5.G i-4.97 i 2ti, rn), 4.'i j-4.70 (2H, m;. ' it', r..) 3.SQ (111, c), 3.51-3.45 (2H, r-t), 3.21-3.17 (1H, m). 2.90-2.86 (2H, m;, -.2.23 ;?.Y, m): 2, i 1-2.08 (2H, rn.;. 1.90-1.82 f lH, m), '..54-1.51 (1F., m), 1.35-1.30 (1H, m), 1.09 (3H, t).
Exa-npYe 45 [l.iQ-(;.r~,?cx.3(i(1R*.,2S*),5(3] 1-3-[7-[12-[(1,1'-Bipheny1)-4-y1]cyclopropyl]amino]-5-(pronylthio)-~ff-1 2,,3-rrigzcr"o[4,,5-d'hvrimidin-3-,ir1.]-5-(hydrnYym,ethyl)-cy,rlopentane-,., zs a) (Y~i-tr~rasj-::-[(1,1_+,i~ipi~c~ylj-4-yl~cyclaprop~~;~ car.box}lic acid Prepare:l a.ccrsrc'.i.ng to the me*.rod. of Exarn.-ole 20, st p (a) iisinQ 1-ethenyl-4-pheny-be*_~
Ni A',t .5'y-i ~ -'fiO,z ) 7,5C,..?,3C (7K tn). 7.19 : ?? --, ;';+ 2.70-2.60 ;
.; Ti rr _), 1 '.?3 (1H, m), :.::+;, 1+~~ ~r.), 1.47-1.41 .1H, m).

b; 1-2-f1, l%BiAeny1)-4-y1] wycloi pxopanamine., [R-(Iw di ~tvu.=r,xybatprii,,cli(,ut:-, ;1:1) Pr-.paxed accor.d?tlg to the method of Example 20, step (b) using the product of step (a).
Ni'~ (t1f'C:;~; 2l0 (Ivi-rH"% iUt?'lo).

c)[3aR-(,3aoa,4a,6a(1R*,2S*),6aa]-6-[7-[ [i-[(Y,1'-Biphenyl)-4-y-1]c,yclopropytj amino]-5-(propylthio)==31I 1,2,3-triazoloj4,5-d] pyrimidin-3-yl]-tetrahy dro-2,2-dimethyl-4H-cyclopen ta-1,3-dioxole-4-methanol Prepored according to the method of Example 1, step (a) using tne product of step (b) and ~e as solve;~it.
MS (APCI) 573 (Iv14-H'% 100%).

d) [1R-[1.a,2oc,3(3(IR*,2S*),5{3J]-3-j7-[[2-[(1,1'-Biphenyl)-4=y1)cycYopropyl]amino]-5-(propNlthio )-31Y-1,2,3-triazc+l oi4,3-d)pyjrimidin-3-y~j-5-(hydr(,xylnethyi)-cyclopentane-io 1;2-6ioi Pre;pared according to the metnod of Example 1, step (b) using the product of step (c).
MS (AYCi) 433 (ivl+H, 100(k) N:vL;< 6:i ;dr,-DMS(); 9.38 (1H, d), 7 64 (2H, d), 7.59 (2H, d), 7 46 (2H, t;, 7.33 (1H, t), 7.27 (2H, d), 5.'0-5.00 (2H, m), 4.78 (2H, s), 4.47-4.40 (1H, m), 3.92-3.83 (IH, m), 3.50-3.40 (2H, m), 3.27-3.20 (1H, m), 3.00-2.80 (2H, m), 2.35-2.04 (3H, m), 1.89-1.80 (1H, m), (4fl, nz), 0.79 (3H, t).

Exnirnp-e 46 j1.R.-1 ia,l(x,3(i,56})=3-[ i-(Bntyiamir~-3)-S-(c,ycialaeiitylthio)-31:+'-1,2.:3-triazoloj4,5-2o dl,,3wrian%(t:iin-3-v1]-5-rhydroxymethyl)-cyclopentane-1,2-dioi Preparecl accoraing to the niethod of Example 4, step (b) using the product of Example 4, ster (a) ~and cvclope~t.an.ethici, followed by the rnethod of Exam.nte 2, step (b) MS 4S7 (IA+H-', I 00%) 4.98-4.96 (2H, dd), 4.73-4.69 (2H, m), 4,46-4.39 (1H, (1V. m), 3.~', (111q, br s;, 3.52-3.43 (4:a, .n), 2.25-:.2t3 ~1711, ni;, 0.91 (3H, t).
Exo;r,~ ,)1e 4,7 [18-1 1:~õ2a,:3~3,5~~15*,2R*)1!-3-(Hyclroxymethul)-5-["i-!(2-lhenyir..yclopropyl)amino]-5--Q tc='r11u ~a or~tth~ h~ phf ny 1iLiaiu]-3i~' 1~2,5 tr.a~;~'~o(ai,5-klpyi ins.lin-3-yr;~
c~~ c:izpeyi t~arie-;i,2 -diol INIre:ct accnrdng to thp methad of ?~xamt9l;: 4, steth (b' using the p~;rritix;t ry;' Exannt<<< slw~ a) ar. d 4-(triftEioronoetnyl)thiopiti nol.
M. p. 10U-1a2 C

. - ~_~--- _--W4 w)9/GSi43 T'CTlSE98/01393 MS (APCI) 559 (M+H+, 100%) NMR 5H (d6-DIW1S ) 9.44 (IH, d), 7.83 (2H, d), 7.61 (2H, d), 7.29 ".08 (5H, m), 4.90 (211.. :n), 4.62 (2i-i, rn), 4.3:21 (1H, m), 3.75 (IH, m), :3.39-3.27 {2.H, m), 3.06 (,H, m), 2.21 (2--1, rn), 2.01 (lF., m), 1.72 (1H, m). 1.40 (1H, m). 1.19 (1H, m).
Example 48 [l, [1 ,~<F2a,3 [i,5R(1.Sx,2R ,'')i ]-3-(Hydroxymethyl)-5-[7-[ [2-(4-phen oxyph enyl)cyclopropyl] amino]-5-(propylthio)-3H-1,2;3-triazolo [4,5-d]
pyrimidin-3-yl]-c,yctopentane-1,2-d'rol a) I Y,6.-t.' a,2(x,:#0.,5[i)1-3-['7-Chioro-5-(propylthio)-3t1=1,:L,3-triazolo[4.,5-a7pyrimidin-3-yi]-5==(hydroxymethyY)-cyclopentane-1,x-dioY
A of [3ar.R-(3aa,4a,Ca,6a(x)1-6-[7-chloro-5-(propylthic,)-3H-1,2.2-ta,.:~,c',o[4,5-d],-yrlinidin-3-yl]-tetrahydro-2,2-dimethyl-4fH-cyciopenta-1,3-dioxole-4-methanol (0.50 g) is in acytc;i.itrale (20 n7i) was stirred with howex 50WX8-200 (1-l+-foxm) ion-exchange resin ((,.49 g; :.t 60 C ftar'l houc: then at room ternperature overrught. 'The resin was removed by -;,Itrazior: and the filr,rate concentra.ted.. The crude product wus pur;fied b"
chr.)l:.la.to;r~-:phy (Si(3,, cd~-.yl acetate as e?uant) to afrord the subti,.le cornpoisna" as a g).
MS 360 (ivl+Ff ', ; VO 'io).
(l~a~-l1~t~1~~~=~~3,5~t"~'~',"~~')]]-:~-(]flyd~roxymethyl)-5-[7-[~2-(4-b) pfieenoxyphPnv!)cy0oorony1] amino?-5-(provylthio)-3H-!,2,3-iriazol.o ~a,5-0~
pyrimidin-3.,.a~a.~,ba~ls~roes~~.anc:
Frepared decordir,g to the tnet:lod of Example 1, step (a) using the products c' step (a) and Ex=amv!e zldõ stel, ard :...ceto:zit:ile. as solvent MS 1Ui '0).
NW ~14 (d(.-DMSC)) 9.33 (1H, d), 7.42-7.34 (2H, m~), 7.27-7.17 (2H., m). 7.1 ?
(lH, t), (4H, .m), 5.06-4.95 (2H, m), 4.75-4.68 (2H, m), 4.48-4.38 ;1H. m), 3.91-3.85 (1tt ,~,. , 3.~u ~.~~- ('.H, 111), 3.21 3.1 3 iLi, ra), 5-2.83 113, rn;, 2.32-2.19 (1H, m), 2.1 ',../L,.,._ ~;.1t, .ri; 1 a.'~'3 C;itf, m), i.e1-1.46 (iH; m), 1.36-4.2 ;;11-(: ir), j_;s'i (3H, t).

C' ~4 E.camplP 49 [lR-[Ia,2a,3(3(1S"*,2R*),5(3]1-3-[7-[[2-(2-Chlorophenyl)cyclrpr=opyl] amino]=-(propylth io)-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-difrl a) ~'1R-tx=anh)-2-(2--Cb.loro;3llenylT)-s:vclopro~ane carboxylic acid Prepared according to the method of Example 20, step (a) using 2-chloro-l-ethenyl-benzene.
MS (t5.it'CI) 195 (M-H, 100%) io b) (lki--t,,ans=)-2-(2-i,'hlorophenyl)cyclopropanamiiie, [R-(Rx,rfx)]-'l,3-dihyairoxybutanedimate (1:1) Prc.~~"uecs Lccording to the method of Example 20, step (b) using the qroduct c: scep a).
Ni;'; (.~ ~ C:i ) i 6ci ~;A t H,? i1i%c}
c)':i ak-132.rv,4a,6a(IR*,IS*),6aaJ-6-[7-[[2-(2-Chlorophenyl)cyclopropyl]amino]-5-(p~-ogylthio,-3.R=1,2,:4-?ria..olo [4,5-cf; pyriffi idin-3-y1)-tetrabvdro-2,Z-dxmethyl-4H-cvr.loprv?xa-1,3.-dio,.-ole-4-methanol F'rQpared according to the rrietthod of Ex mpie 1, step (a) using the product of step (b) and 1,4-ciioxane as sotvent.
M:i ('J'CD 53 4{:~1 1(10 Io).

d) !iR-i 1a,2a,3(3(1S*,2R*),50]]-3-[7-[[2-(2-Chlorophenyl)cyclopropyl]amino]-5-(pR 4;-:i Y-i,2,3-trt~-zoVo[4,3-dJpyrimidin-3-yl]-5-(hydroxynxethyl)-cyclopentane-2s F~: ft:re ~:c";+)..irr.g r'tie .r,r!tnoc: of rxunl;a.e l, step (b) usinà Jit-F,:odsct o: s.ep (c).
41'7. lfju 1,)) P1I~~tz ~4-! rd5-1~MS~i- 9.38 (1H, d), 7.43 (1H, d), 7.30-7.22 (3H, m), 5,0?-4 9,F (.2.H, m), 4 1 i 13, 3.91 (III, rr.), 3.52 3.10 (2H, m), 3.00-2.80 (2I-7L, (3PI, m;, 2.13-2.,02 '1H, m), 1.93-1.81 (II-I, rr.), 1.70-1.33 (=11I, m), 0.80 WO 99103143 t'CT/St?98/01393 Exani,.,le 50 [1S'-[1 cx;,:2a,3 [3,50(I5'~ ,2R*)] ]-3-(2-Hydroxyethoxymethyl)-5-[7-[(2-phenylc),clop ropyl)amino]-5-(propylthio)-3hl 1,2,3-triazolo [4,5-d] pyrimidin-3-y1]-cyclopentane-1,2-=diol a) ["al~:-[3aa,4tx,6a(1R*,2S*),6aa]-N-[(2,4-I)imethoxyphenyl)methyl?-3-[6-[[2-[(1,1-dimethylethyl)dimethylsilyl]oxy]ethoxymethyl]-tetrahydro-2,2-dimethyl-a1~=
cyclopenta-1,3-dioxol-4-yl]-N-(2-phenylcyclopropyl)-5-(propylthio)-3H-1,2,3-triazol o [4,5-d] pyrimid ine-7==amine Sodium llydrlae t35m;, 60% dispersion in oil) and (2-bromoethoxy)-tart-butytciimetnyisilane (0.2m1) were added to a solution of the product from example 36, step (b) (31'1.r.g) in toluene (3m1) and the reaction mixture heated at 65 C for 6h thc~. at 100 C
for ia licur<.,. rurtrr.er sodium hydride (33mg) anct silane ((1.2m1) were added and the 1s mixture heated for 6lnours. Amrrionium chioride solution was adctea and trre maxture was ext=act=~r1 w;.th ethyl acetate. :'he organic extracts wefe dried, curicentrated and purified (SiCa,,. ,,i.~rol:eii,e.r 2:1 and ~e'rol:ethyl acetate 4:1 as eluantl to give the subtitle compound (77.r NMR SH (C.:UC'13) 7 2';-7.12 (6H, m), 6.40-6.28 (2H, m), 5.37-5.17 (3H, m), 3.79 (1H, m), 3.78-3.73 (5H, m), 3.6-3.51 (7H, m), 3.1-2.95 (2H, rn), 2.6-2.1 (2H, m), 1.68-1.61 (2H, m), 1.59= l i7;6H, m). 1AR-1.41 ( i kif, m), 1 3()-1. 21(S:! i, m), 0.94 OH, t), 0.86 (yN., s), 0.06 (6H, b) 1 ~1?~-t1-3-(2-hydroxyethoxymethyi)-5-17-1(2-phc-t3=i--j=clcprof-),i)azn:noi-='S-(propyitiiio)-3f1'-Y,2,3-triazolo[.:i,5-ci~pyrimidin-3-yl]~: taaalerit:ta~~-1,~!-E~i:ol Pre:p,irvõ' ,~ :~rcizng to ~re method of example 2., sten (b) using the product of step (a).
Purification (iriPLC N'ovapaic"' C18 column, 0.1% aqueous ammoniurr~
ac,eJra*P:,ac;etonitrile, isoc:,,t r_1-~eCN o1e'. 30 n1i :u.tes; :f;=oru:.d tl.e title c(-rriroo.- d (.:~R71;).
MS (Ea_a _.: ' 50 1 1 ; : ,: r,U%) NNIFt 5P. (d<WrMiC't 9.35 11-7, s), 7.:741-7.05 (511. r.r. 5.09-4.9 _. (: 1=1, cr ), 4.f,1. (1 H, d), :3.90-384 (1H, rn), 3.6-3.3 (8H, rrm), 3.24-3.16 (1H, m), 3.01-2.'7y (214, m), 2.35-2.08 (3H, m), 1.90-1. 7t1(1H, m), 1.56-1.44 (2H, m), 1.37-1.27 (1_:t., rn} 0.80 1! .3H, t;.

WO,)<*105143 PC1'/S1:98101393 Eaample 51 [1R. -[ 1 cx,2(3,3 p,4a(1R*,2S*)] ]-3-Hydroxy-2-methoxy-4-[7-[(2-phenylcyclopropyl)amino]-5-(propylthio)-3,H=1,2,3-triazolo [4,5-aipyrimidin-3-yl]-cycl pentanemethanol (a) jiR= [la,2a,:$b(!R'*,2S*),5kr]] -3-[7-[lU=(2,dr-Dimethoxyphenylmethyl)-(2-phenylcyclop ropyl)amino] -5-(propylthio)-3H-1,2,3-triazolo [4,5-dJ pyrimidin-3-yl]-5-(hydroxyme thyl)-cyclopentane-1,2-diol A solution of the product from Example 36, step (a) (1.39g) in trifluoroacetic acid ro (1.:iriu)/methanol (15mi) was stirred for two days. Ethyl acetate was added and the mixture was concentrateu. Sodium hydroger, carboriate solution was added and the mixture was extractea witn ethyl acetate. The organic extracts were dried, concentrated alld purified ,-'aml:acetone 1:1 as eluant) to give the subtitle compound (1.11g).
Ms (~,~~.1) bui (iV1+i-I-" i00%) 15 (b) ;1'i ~h~(:'1,~1-Dimethoxyphenylmethyl)-[{2-phw~~yl+:yclupr~'pS'i)aminn,y=5-(p"~ol y9tlzio)-?.fi' 1j2.,3-tri.r;-ulo[4,5..,~p:
[[[(1,~1-di~~t;~~hylethyC)~r1~:ph~;:aylsilyil] c~x.yjmeth~l]-:
yctcrpet~~t~ne...ly2..di~.~l A soWtioa :.,i tlie pi7oduct ui s..-p (a) iail:-la::vl~; (441 ; nlg;
butyl:,rsorudipheliyls-Aaile (0.75 m?) en dry 1:-J!1F (42ns) w?s stirreu ior _S ) hours. "Yi'ater was 20 ad~: i.r ;' :ie mixture was ext2=---:Led wif;r eihyl acetate. Th;: organic extracts v~:ac dried, cor.cciitiatpc...nd l;u-ified (5i02, petrol:acetone 3:1 as eluant) to give the subtitle compound (1.16g).
Ntv!_ t ()'.f (1oH, ni), 6.44-6.30 (2H, m), S.6:3-5.63 (2H, rn), 5.45-5.31 (11-1, rn), 5.0= -4.'18 (),4, -n), 4.50-4.4(1(1H, m), 4.3-2-4.27 (1H, rn), 3.b0-3.51(8H, In), 25 3.D-9.63 (4H, rr2), 2..53-2. t7 (3H, m), 1.79-1.40 (4,q, m), 1.01. (9H, s), U 97 '"H, t).

(c) 'ilS-[]ta,2oc,30,50(1S*,zlt*))1-5-[7-[1V (2,4-Dimethoxyphenylmethyl)-[(2-pher y~cyc)opropu~)a:i~riz~c~ll-~-(;propyrthio)=3fi-1;Z,3-triazolrrl4.,5-dlpyrirnidin-3-y1]-3-[[l(),1-clrnietnylethvt)P.iiphenylsilR 11 oxy]metlryl]=2-mpthnxy-cyciog zntan.ol 30 Sod-;Y,,z t,vdrirte (5~.3rnL )v,s.s addPd to a sa'u ion of the diol from stPo (b) (J .23g) and rrc...t i -. )+~d~ci.e ((1 ~?m1,1 in !~?~i~~ (4m_() ?_nd the mixture was sti-rM, for "h. Ammonium ch)._)r:aa sei?Itiori was ad 1Fri<<w.'. the -:-~ixt.;:+re was s. ,=arted with etnyl ~~~tate. '::'ne organic ex(rEar,t7 ix,ere ~~ried, ecnc;r-?rated and pLirified nci T),:u:jl:ethyl ac,~t. rf 7:1 rj~ givc the stibtitle ccmnou.r.d. (676m;;) as a].:2.5 mix*?:re;
with the .35 reJi~ ~sorreric ro,,2cx.:s~3,5~~(l.~?",2:i*)~.!-3_[%_~;hr_r2,/~--d'tmett~nxyr.hf ryt t,e''~vl)-(2-Wr;') 99/05! 43 1'C'r+SE98101393 6i phr:ny.tcyc~:sprop:,'1',a171.i~no]j-5-p.opylthic-3H-'.,2,3-triazo'o[4,5 cjyay.~'in-jdi.n :z di~i-iethyleth:yl)cliphenylsilyl]oh y;riethyl j-2-m(,thoxY~ cyclope:;,t:ino1 cc;rn,,_;ouad.
NMR 31-1 (CDC? 317.5 -7.0 ~ 1 il-I, rn), 6.43-6.31(211, in), 5.84-.4.6C (41, rn), 4.:35-4.27 (1 H, m),. 332-3. 1-:2 (1 l. H, rr.) 9 3.15-2.85 (2H, m.), 2.64-2.58 (1 H, m), 2.53-?- .97 (29, m), 1.77-1.221,5H"', l.Q l (9H, s), ~).97 (3H, t).

(d) [1R-[1a,2(3,3(3,4cc(1R*,2S*)]J-3-Hydroxy-2-methoxy-4-[7-[(2-ph~ny l -.yclapropyi)amino]-5-(propylthio)-3H-1,2,:3-triazolo [4,5-d]
pyrimidin-3-yl,j cyc lvpe[nt.anemethanoi A solution of the mixture of coinpounus from step (,.;) (b"76mg) in triftuaroacetic acid -water (9:1) (3m1) was stirred for 20 hours. 'I'he solvent was removed in vacuo and the residue was :yissoved in il-iF (lml) ana treated with tetrabutyia.mmoriuni fiaoride in THF
(.'. -c.;:, i: oiution) and stirred for 4nours. The solvent was rem,3'red i 4 u;ina the residue purified (Si02, petrol:acetone 2: 1, dicl=:loromethane:methanol 29:1 and petrol:ethyl ace;ta~e 1:2 as eiuants) to give twc, fractions:-F'~'~:avt ~.~]-3-l~yiir~~xy-2=rrretlx~,~v-4-['1-[~'?-pk~e r~~,r.~clooro~y~arrxzn.~a:~-5-(r,ronv(rhic~)-3~I 1.,2,3-tr~azo~.of4,5-d'lpyrier,idi.r-3-yt~c; c Per.ta.7:,m t;13noe.
Fracti(ir- 2, 330mg, 1iR-[1a,2~,3fi,4Ãx( iR*,2,fi*).11-2-hydroxv-3-rnetnoxy-4-17-[(2-ph nys,c inpropyl)arnino j-5-propylthio-3F1-1,2,3-triazoio[4,5-d~pyrim.zd;n-:s-yi jcyclopentanemettranol; further punfied in example 52.

Furche ' r}urificatiorr of fraction ](HPII.,(~. Nova.pak C l8 colurnr_ 0.1 610 aqueous aj;1n.t;;;zlani ;,;: eta isociatic e'tutior. 45 sc itiieCIN ovcr 40 Iliilluw.s) afforded the tl:.l; ..C1I[UJGu 1G

Ni'/i~;. 6H ;,aF 1)v.: b;y), '7.341-7.13 (SH, :~.60-4.49 (1H, m -'1. ;7 tl, s), 2.32-2.0-7 (3H, m), 1.92-1 Kii ~' jF, xj, i.;C?-.?.47 (3H, m' ,:' .38-i .?.~ "th, m), 0.80 9 1-i, t).

6:7, Exazndle 52 c~:,2p,3(3,~4ct(1j!Z*,2S*)]] y2-Hydroxy-3-methoxy-4-[7'-[(1~-ph;enylc.yclopro pyl)amin o]-5-(propylthio)-3H-1,2,3-triazolo [4,5-dJ
pyrimidin-3-yl]-cyclopentanemethanol Purification of fraction 2 from Example 51 (HPLC, Novapak C 18 column, 0,1%
aqueous ammonium acetate:acetonitrile, isocratic elution 45% MeCN over 40 minutes) afforded the title compound (133.5mg).
MS 1t?.i'Cl) 471 (M+H+,100%) NlviKAti (d6-L' NiSU) 9.35 (1 i-1, s), 7. 34- 7.13 (5 fi, m), 5.14 (1'rl, q), 4.79 (1H, s), 4.23-4.05 (2ri, in), 3.5'-3.25 (5H, m), 3.2:i-3.18 (1H, m), 3.04-2.79 (2fi, m),1..s7-2.G6 (3H, m), 1.9~, ~.BU (iH, m;, 1.60-1.47 (3H, m), 1.38-1.28 (1H, m), 0.83 (3H, t).
Example 53 is [1~>.(I~t,Lcx,3~3(~),5~(t.5*,~X*)]]-3-(3-l~ydroxy-prop-l-enyl)-S-[7-[(l-ph,, rNvieyc'(;'Nprop yI)arnino]-5-,(propylthio)-3H-1,2,"1-triazolo[4,5-dlpyrim:irlin-3-yl]-c!/

a) 3-ti.3a.FC-,13sa,4x{.F;,6cx(1R*,2Sx),6aa]]-6-r7-[(C'yclopropyl)amiino]-5-(propylthio)-3I,1-1,2,3-triazoio [4,5-d]pyrimidin-3-yl]-tetraihy dra-2,2-dimethy--WH-cyclopenta-1,3-a.cid, meth.yl ester A soiut.ion of the product of Example 1, step (a) (1.6g) in d:methylsuiphoxide ;15m1) was treated with pyridirzf. 0 :75g) followed by trifluoruacetic aciii (0.1 3g).
'fo this mixture was ( l.y9g). After sdrring ior 5 nouis at the reaction :,i ,,,1tL1 (, .72g) ani then sti:rc : for a 12 ';.au:-s. T2;; :iii.xtu;Nc wa3 paiz ,PC+ Into ethyl a;;e:
f:: (':)Ci';nil.', and tre.3:u: ,::itlfl ;xtt,i, rc :(1.5S+g). .3fter stirring for 30 minutes the mixture was fiitered and the eth: t acetate solutior, was washed with dilute aqueous sodium bicarhuna,e and then witri c5: ~te .,:queous b:t7ne, before being dried and coricentrated.
PurificdtLon (SiJ2, ethyl !:,! ai e1'1c.I?.t) aii0rac;'j tlie Ãl+bdtl., ccm.pouni' N+.u= t.1;.:'C1:1 55l (M+?i *, 100%) b) 3-([tR-[1or,(E),1P,3P,4oc(1R *,2S *)J1-2,3-llihydroxy-4-[7-[(2-phen3rlcyclopropyl)aminol-5-(propylthio)-3H-1,2,3-triazolo[4,5-dijpyriniidin.-3-y1]-cyclopentyl]-2-propenoic acid, methyl ester Prepaa.ed according to the method of Example 2, step (b) using the product of step (a).
s MS ',',17'MO 511 (M+hr', 100%) c) [1S-[1a.,2a,3[i(-E),5[3(1S*,2R*)1]-3-(3-Hydroxyprop-l-enyl)-S-[7-[(2-phcnylcyclapropyl),).nnino]-5-(propylthio)-3H-1,2,3-triazolo [4,5-d]pyriznidin-3-yl]-cyciol3entune-x,2.-ciiol io A sor.rtron of the ~roduct from step t;b) (0..7g) in tetra'tiydrofurai ~'25n-.l) at -i8 L was treated wiyh Di1y.AL-ri" (1.5 iVi solution in toiuene, 8.2m1). The rnixture was then stirred at 0 i; for 1 hour before being quenched with methanol (1mi) and tnen poured into dilute aqueous sodaum hydroxide (50m1). This mixture was extracted with ethyl acetate (200m1), the extract was dried and concentrated. Purificatiori (Si02, ethyl acetate as eluant) afforded is the titlc: compound (0.2g).

NNirL fxH f~,,-1*t~iS4:1i 9.34 1H, d;, 7.31-7.15 (5H, -,r), 5,.80-5.70 (114, m). 5.65 --5-58 (1H, m), S.09 (lfll, a), 4.83 11H, ci), 4.67 (1I-I, t), 4.33 (ilz, q), 3.93 (2H, t), 3.84 (114, q). 322-3.1 S 3.00-2.80 (214, m), 2.65-2-6() (11-1, rr ). 2.42=-2.38 ; a Jt1. m), 2.15-20 2.10 ( t:1., *n',, 2.00-t.85 (lri, *n),1.55-1.47 (3H, m), 1.35-1.30 (lti, n:,:), 0.85-0.80 (3H, m).
Exztnpie 51 ~'*,'uR*)~1-3-(3-Hyd.roxyprop;l;-5-[7-[(2-pi~Era~~lc~rcl_~Fero1~~,'.'y.~:~inQ;_5 (pr pyif;r~io)-31~'-X,2,:i-:riazolo[1,5-d1pyrimidin-3-ylJ-25 cy0t!;f1i:1A'a:,C i;1 4171.1 A SJ:It'=.ior, of tl?F' o'O'~'.1CL of E7i:~rn?~.Je :oJ, .StP.p ((%) (44.' 2g) and.
tr?lsc~~~~r,.yp.,/-',henzenesutohonylkrydrazide (0.3g) in tetrahydrofuran ( lOm1) ti-as ~eated at 70"C for 4 hours. The mixttare was then purified (SiO2, ethyl acetate as elua.nt) to afford 30 thF ti .l(~ c.O-,1c.o_jn,', (r.:! 3g).

D~~.,,. .~)U-4.~~~ 1~2rn'~'.~~:~ Ql1f d), 4.4:-) -!.'r= rni. Y'= i3 ('.11, q), ~s 41 (''.ri, (1I1, m) 2.93-2.E;3 m), 2.37-2.:; :)' t111, .,=;, 2.1 J~--::=' 1(1H 1=95-1.85 (1I-?~~:., rs'), 1.7 7--?..31 (1)II, r:a). O.Q3 i311,t).

WO 99/05143 PCZ'/ ' )E98/01393 Examilv'e 55 1-[ [1S-[1a,2(3,3p,4a(1S*,2R*)]]-2,3-Dihydroxy-4-[7-[(2-phenylcyclopropyl)aminol-5-(propylthio)-3H-1,2,3-triazolo [4,5-dJpyrianidin-3-yl]-cyclopentyll-2-methoxyethanone Bortin trirluoridq, etherate (1.0 ml) was added to a solution of the diazok *cme. prepared as described in Example 8(0.60g) in methanol (50 ml), and the so'ution heated at 50 C for 1 hour. The reaction mixture was extracted into ethyl acetate and t,le extracts washed with water then dried and concentrated. Purification (Si02, ethyl acetate:dichloromethane 2:3 as eluant) atforded the title compound (0.16g).
MJ (11PL1) 499 (IV1l+if , 100%) NMR dH (a6-ilMS0j 9.36 (1H, a), 7.3i-7.16 (5H, ni), 5.25 (2H, n), 4.99 (li-i, sn), 4.30 (1H, rn), 4.24 (2H, m), 4.13 (1H, m), 3.21 (3H, s), 3.19 (1H, m), 3..13 (1H, m), 2.96-2.83 (21H, (2H, m), 2.14 (1Fi, m), 1.5i (3H, mi), 134 (ihi, m), U.bi (3r:, c}..

Example 56 [1S'-=11 (x;2r,.'s~,S(i)1-.3-(1'rlydroxymetiryr)-5-[7-[l(trans)-L-(3,4-mexhv ie-iedl-,)xyph.eMv!3cyclopropyljaminn]-..5-(propylthio)-3N 1,2.3-triazolo[4,5-dipyrimid'rn-3-y1J -cyclouentanp4,2-diol a)[3ak==i'3asx,4a;6cc,,6afil-T'etrahydro-x,:'-ciimetk-vl--6-[7-[[(tratrs)-2-(:3,4-methylPr.edi7.x<Tp'herryl)cy~loapropyllnminol=.5-(pronylthio)-3.Fi.-1,:.,3-trAazotca [4,5-dJ pyrir7 idix--3-y1]-4.Fl=c,yclopenta-a ,3-dioxale-4-methanol Prepared according to the method of Example 1, steO (a) using (trans)-2-(3,4-met , i:;n ci: ?xYp}~~ n~ileycloprc,nana nine hydraehloride.
M:.y IrJI.:1' 44' (N. Fõ+, b) j1.S (1a,:;a.,3[i ,5(3)]-3-Hydrexymethyl-5-[7-[[(tr ans)-2-(3,4-m~~:;1r.:.r.:.r,~xy~t~eny4jcytlcll"oPyljar~in~ss-~-(l~ropylthic)-3~~1 lik4,5-djpyz in.lttin-.~-y:j -cyc:lopen tune-1,2-aiol Pr::,jarerl a c<~arc:ing et.e mcthod oi'Lxample 1, step (b} using tt.c:
p.cduct of st--,p a).
M:i ~~+=~.::- fv ) i -6-:AA "W>>
NlVx<. o1-i (OF, ") (2H, m), 6.71-6.69 (1111, -n), 5.96, (2H, s), 5.014.~4'7 !.?ri. in), 4 11-4. % 1 1 ?'H, m), 4.44-4.40 (1H, m), 3.87 (1H, q), 3.51-3.44 (2H, m), 3.1U-.3.G7(lri, in), 3.00-2.90 (lH, m), 2.27-2.23 (lff, m), 2.08-2.05 (2H, rri), 1.86-1.83 (lE, L-';.

Example 57 [1S -[l. ct,? a, 3~i,5~3('~S*;2I: *)~ J-3-(H ~dro acymethyl).5-[7 .[[2 -(3-.
methoxyph eqyl jcyclopropyi] amino j-5-+propyii:hio;l-3'H-1,2,.3-tria:colo j 4,5-djpyrimidin-3-yl]-cyclopentane-1,2-diol a) (3aR-[3aa,4a,6a(1R"",2S' ),6aa]-Tetrahydro-6-[7-[[2-(3-methoxyphenyl)cyci.oprop~tl]amino]-5-(propylthio )-3H-1,2,3-triazolo[4,5-dlpyrimidin-3-yl]-2,2-darnethyi-4H-cyclopenta-l,3-dioxole-4-methanol Prepared according to the method of Example 1, step (a) using the product of Example 24, 10 step ie MS (faFCI) 527 (nd+H', lUOvo).

b) (.tS-=jlcx,2a,3p,5(3(iS*,2R*)11-3-(Hydroxymethyl)-5-[7-[[2-(3-met:nox),pnetryl)cyclQpropyljamirno j-5-(prupyithiu)-:Y'lZ'-1,2,3-triazoloj4,5-dJpyrimidin-15 3-yij-ws=c,opentane-i,'-dio:
A s{JW: cn ~r' the product fror.7 step (b) (0.29 g j in 8U~io aqueous acetic acid (10 ml) was hence-i at 8t; fo- " hol7r. '? '-.e sohjt?nn was cor:centrv1r.ed in -ca.-uo and puriried'oy chmni,ttagTaphy (:tiK2, meth: nci1 : (?ich!crnmeth-3ne. 3:95 as . ,1,;:ant) ro cnide pro~uci. FGirther Durif:cation (HPLC, NovapaVC18 column, 0.1% aqueous ammonium 2o acetate:a.cetonitrile, isoclratic elution 45% MeCN over 15 minutes) afforded the title corcpc;;r.cd, as a coiouriPss s-li(j (0.19 g).

M~j'(A}'C'[) 48'7 (1v1+1-f', 10011/o) NIv?:3,1 i,li ic1F-1~'vl,ti~; 9."'52 (1H, d), 7.19 (1H, t), 6.78-6.72 (3H, m), 5.04-4.95 (2H, m), 4.I:i-4,69- 4.47-4.38 (1fi, m), 3.91-3.84 (1H:, m), 3.75 (3H, s). 3.55-3.41 (2H, m), 25 3.24-.s.i ,!,1Y:, ld-), 3,by-2.91 (?l.i, :i,õ 2.~0 ~.i;~ til1~v 1T1;, 2.3 1-2.19 (17:1, m), 2.i4-2.04 0,6:i Ex:a-~:rr~~ 5'~

30 h3=tlrc c}c ;srap; 11:~1a~1L1u1-S-~1~LC~l1~~Itllyc;-3:';
3=yi~- ~=,:1~+,-i;:.+~sr,,E--1,'r=,ir:~T

a) '1 iK.,.erar+,1.,-1 I..i-':vcirox=ypbenyr,~=ryrlopropanam~~ne, hvdr.'a'~?roraicif!
A ? :r.e trFe rf t1=ioc!uct: fro;-n i;xanal:-le 20, ster, (b), (300rnlg~ i.n 47%
35 aqueo2::s hvdrobromic acicl (9 ml) was he4ted at 100 C for 2 hours. Tbe rea.ction mixture wa? con.":n:.ratedzncl the rey;d'",e a.Neotroped witl=, tuluene (3 x 30 lnl).
The residue was WO 94/014p PCT/SE98/01393 thei~ tar.e-a ir Ãc, eth.ar.0: ''7 :.nl) 4Lad itae p~:oducr precipita.ted by the slow aLditi ;r. of ether (100 rru;i to Lfford th:, subtitle c.otnp3und (290 mg).
N11"N bE (D.,J) 6.98 (:%,H, ni)õ 6.74;IH, m), 2.68 (1H, m), 2.25 (IH, m), 1.25 (1H, m), 1.14(1I1,m).
b) [3alr-[3acc,4a,6a(1R*,2S*),6aa]-Tetrah~Tdro-6,-[7-[[2-(4-hyda-ex rphenyl)cyclopropyl]anaino]=-5-(propylthio)-3H-1,2,3-triazcrlo[4,5-d]pyrimidin-3-y?']-7.;2- 3iL:.~eth1 F-~i~ ~ cyclopenta- .,3-dioxole-4-me thanol Prepared accoraing to tt-e method of Exampie 1, step (a) using the product of step (a) and tetra'-iv*ofu;,an as solvent.
MS (A?C:1) 513 (I1~i=+Ii , 1000:).

c) l'k)]]=3-(Hydroxymethyl)-5-[7-((2-{4-hydroxyphenyl)cyclopropyl]amino]-5-(prvpylthio)-3H-1,'L,3-tr=razolo[4,5-r1]pyrimidin-is 3-ytj-c}rclopentane1;2-ctiol Prenared r:ccordi~Ifr to ttie: mPtnod of E.xampie i7. strn (h) using thL
product of stec- (b).
MS (A ''+Cl) 473 (:M1l E1T': 100%l.
N1O:r;. ?.-i .(~ =t~?~~~') 9.25 (1H, d), 7.05 (2H, dd), 6.59 (2H, dd), i.62 (4H, rr), 5 00 (1H, m), 4.4 1 ( i i::, m), :'s.8 7 (1ti, m), 3.45 (2H, m), 3.05 (1H, m), 2.95 (2H, m), 2.27 (IH, m), 2.06 (2'R, na), 1.86 (1H, m), 1.54 (2H, m), 1.39 (iH, m), 1.20 (IH,m), 0.87 (3t1, t).

Exn,mp"e S9 [L'i.j1~~:.Zrc,.~t~,5~>(1,'3 :yZit*1]]-i-(Hyd.~-oxymeth;~l)-5-[7-t[2 (3-me~::~wElylre,~~~1)cys;,~~}~i~.ax~yi~~.ra~tl.r,] -(prcopyltiai~)=;~~i~=1,2,3-triazUi4,?4,,~ -a']h3rrirnidin-3-zs y1]- + : .~~va ,r~t ~txf: ];i;-cJaai a) 1:3a.Z-'t3auy4cx,6(c(iA*,2S*),6aa]-7 etrahydro-6-[7-[[2-(3-met4~-0r henul)cyrlo~ rapyi'r rainfl) = S-(pro_fly)thi r3)-3F-1,2,3 -txrazoio(4 ,5-t1lpyrimidin-3-y1] 2.,2_~l ~z:~a~~,hy-i-~J~1=c~cl~,pex~#a41,:3-rliaxa~.:1-rnt;~ ~auc.l Pre,-,aj e# a;:,. yrc;inlj :7 :.e of Exar_:pie steC) ;u; using tl.e piouuct of :=;:cGrnple 25, ste,r.(r ;.
MS <<\'Ir::i.) : 1 !. o/,',-1;':', 'b!.

WO 99/05143 PCT/.iE98/01393 b) [1S= '[l a,2a,3(3,5(3(1,S*,2R*)]1-3-(Hydroxy-nethyi)-5-[7-[f2-(3-methy}:phenyl)cyr.lopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo [4,5-d]
pyrimidin-3-yll -c;yelopentane-1,2-diol Pre-oare:d accordinn to the rnethod of Example 57, step (b) using the product of step (a).
MS:'':'A) 47 fM+f~ , 1CrO%',. NMR E__i (d6-OMSO) 9.31 (1H, d), 7.17 (1H, t), 7.07-6.93 (3H, m), 5.06-4.94 (2H, m), 4.76-4.68 (2H, m). 4.48-4.38 (IH, m), 3.91-3.81 (1H, m), 3.56-3.40 (2H, m), 3.21-3.13 (1H:, m), 3.03-2.8'. (2H, m), 2.29 (3H, s), 2.27-2.18 (11-1., m), 2.16-2.02 (2H, rrm), 1.92-1.78 (lf-:, ar: j, l.ou-i.43 rs,) 1..'7-1.26 k'iI3, n7;, 0..84 1"31-I, t).
Exaan.~rle tiu jl~-~~a,2a,31~,5b11S'*,21~~~1] J-3-(riydroxylnethyi)-.S-Ji-[(i-(3-phenoxypnercyl)cycloproPyijamino]-5-(propylthio)-3H 1,2,3-triazoloJ4,S-djpyrimidin-3-y! j-c,yclopentane-1,2-diol a) ~*):~aa]~'~'etrahydro-'Z.2rdimetl~yl-~-[7-[[c-(3-pheno ryplr, enaJ)cyclonrol;l,l]amilloa-y-(propy Ithi6;-3f{ 1,?,3-triazolo[4,5==d(pyrimidin-3-y11-4V-cvcloneitt4-1,3-,Jioxole-4-methanoi Prerwf:4~ arw.c,rd,~ha, to the m.ethod. nf'I~xamnle 1., step (a) usirg the product of Example 29, stP'S (c;

LVI.~ ~,A.PCI) 5i.i4 (M+W, 100%).

[1.S-~1cx.,~:x,3~i,5~ir1S*,2R*)]'-3 (llydraxymet4~yl)-5-[7-[[2-(3-b) p~.,,r.~;."rp r:'.e ~'A~C'~'~~e'2r4*~',y'1+ q~ritTli i'-'J-(pIYI'If;'_tIt} D~
25 Pr~ r?r ,:: d~ ~:~r~ ing to t= method of Example 57, step (b) using the product o=' step (a).

M' i-,1T, N.)i',' 'JI 9.32; iII, d), 7.41-7.38 (2H; m), 7.30 (1I-I, t), 7.01-6.1~5 ;"I-i; m), 6.9:5 (,I-i, s'-, f;.&C i 1H, dci), 5.C,1-4.96 (2H, r.1), 4.73-4.70 (2H, m), 4.45-4.38 (1H, m), 3.51-3.45 (2I-I, rr;, 3.10-3.18 (IH, .7i;, 3.33-2.81 (211, m), 2.31-2.22 (lri, rn;, 2.15-2.06 (2H, m), 1.8:'-11.9 1 ( t.1i, n.',, 9 (3 H, sa),. 1.33-1.";() (1F', r~)" 034 (:~H, t).

WO 99/0;143 PCT/SE98/01393 ExaYriple 61 [1R ;~S*),55]]-3-[7-[[2-(4-Fluorophenyl)cyclopropyl]aminol-5-(prr: _=y1tF'Iicy-3I-1=1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxynuethyl)-cyclopentane-1,2==dia::
a) [a ad'-[3aa,4a,6a(1R*,2S*),6aa]-6-[7-[[2-(4-Fluorophenyl)cyclopropyljamino]-(propylthio)=-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yl]-tetrahyd ro-2,2-dimethyl-4H-cyclopenta-l,3-dioxole-4-methailo:1 Prepared according to the method of Example 1, step (a) using the product of Example 19, step t;i).
MS (kPO) 5 1.5 (M+{-f', lUo Io).

b) ~1.1.=~,"I.c,:,.2a.,3p(1R*,2S*),5[i]1-3-[7-[[2-(4-Fluorophenyl)cyclopropylianiiriol-"r (pr oipylthio)-3H=i1,2,3-triazolo(4E,5-d)pyrirnvilin-3-yr]-3-(ilydroxymethyi)-cyclopentane-ts 1,2-ciot Prepared aceording to the rnetriod of Example 57, step (b) using the product of step (a).
MS Arc:
NMP ;'"'' (0_-DMSO) 933 (1H, 6)., 7.19-7.17 (2H, m.), 7.17-7.07 (2H, m", 5.0f_a.95 (2H, m), 4."16-4.66 (2H, rn), 4.48-4.38 (1H, m), 3.92-3.84 (1H, m), 3.55-3.41 (2H, ni), 3.18-3.05 2o (1H., m), 3.01-2..81 (2H, m), 2.31-2.19 (1H, m), 2.18-2.04 (2H, r.z), 1.91-1.79 (1H, m), 1.53-t 4c; (:3f-I. rt), 1.36-i.2t, (i'H, tn), 0.83 (3H, t).
Ex~mnle 62 [1S-t1 ~c,~+.x,:~;i,S[i~:1S*,2R*1~~-=3-(H~droxymethyl)-~-[7-[[2-{3-nit-c~Fii~anyy)c;yclopropylJa.mina?-5 (~ropylt},aay-3:I
yl]

a) Tetrahydro-2,2-dimethyl-~i-i7-ff2-(3-nitro;ot?.En;h,cytc}~rcpylla~n~rk~'_:_i.propy't~mo)-3fI-1,2.,:1-triaaola,~=;,r;-crp~~a ipr~:idin-3-3o yl] -'.~~ ey~c1 rpenta-l,3-di~ixole-4 me kha nol Prehvi,,,,_ tt, " :he r=oth,):' Exa.rnn!e 1, step (a'using thc product of Example 27, stec u;.
1VIS SA:) b) [1.S-[l.oc,2a,3(3,5(3(1S*,2.R*)]]-3-(Hydroxymethyl)-5-[7-[[2-(3-nitr olzli(,nyl)cyyclopropyl]amino)-5-(propyfthio)=-3.H-1,2,3-triazolo [4,5-d]pyrimidin-3-yl] -c:yeacpercd-ar-e-1,2-diol Prepareci ar.ccsr?.ing to the method of Example 57, step (b) using the product of' step (a).
MS !AP(:P 502 (rM+H+, 100%).
NiVIR :3I=i (d~-DP!IS 0' 8.10-S.00 (2H, m), 7.71 =.7.55 (2I-i, m;, 5.06-4.92 (2H, m), 4.82-4.64 (2H., hr), 4.47-4.3) i~(ll~, m;t, 3.91=3.83 (1H, rn), 3.55-3.41 (2H, rn), 3 28-3.20 2.97-' 2.?2 (2H, m.), 2,37-2.17 (2H, m), 2.16-2.03 (1H, m), 1.92-1.77 (1H, m), 1.74-1.60 (lI-x.., rrlj, i.59_i.39 (3H, m;, 0.'15 (311, t).
Exarr,ple 63 11R-[lc4,2o:,30,50 (1X*,2S*)]1-3-[7-[12-(3-Aminophenyl)cyclopropyl]amino] -5-(propykt,tpiv)-3H=1,2,3-triazolo[4,5-dlpyrimidin-3-yl]-5-(hydroxymethY;)-cy cYopentane-1,2-4ioi Preprredi by tlne method of Example 30. lasing the prc+duct.of l:xample 62.
MS (i~.'~'+':I) .*71 (M+H+. i.U+, 4k).
NIVII: 89 (d6-I7MSO;~ 6 91 (IH, t), 6.42-6.29 (3H, m), 5.07-4.86 (1H, m), 4.49-4.38 (1H, m), 3. 9l-3. 8 5(l. H., m), 3.56-3 = 40 (2H, m), 3. 23 -3.1. 5(1 H, m), 3. l 4-2. 84 12H, r-i), 2.32-2.18 (IH, m), 2.1'i-'.~.0S (iH, rn)I. :;.G5-1.,6 (IH, m), 1.91-1.78 (IH, in), i.64-i.50 (2H, m), 1.46-t !ti (:.iH, m). i.2K-1.i.3 ~iH, m), 3.87 (3Y, t).
Exarnp?e 6=1 [LS' ~ s 1~-'I. ":"..(3,5-DiL=aeuhc:qphenyl)cyclopropyl]amino]-5-zs (pra~<y~r~ioy-~L~~-L,2,:;-iria~elo[4,a ~';~Yricrei~:.~r ;3.yi]-eyelopewitane-1,2,3-tr~cy acid To a~~,i. t on :~t 3,5 c~imeu~uxyoen~aldehyde (12.5;) +.n pyridine (20 ml,) was.irlciee.
mawn,c ac.lkt (6.61g) a;id piperidme (irnl). ''re resultirig solution was hea,.ed at 100 C for 16 :Lcurs, cc,uied to ro~7.m te.mperature,, pourEd onto ice arid acid:fied u.c:lg ::IC1. The resutr.~o>y ~.reanitat ~us ccliec~t".,?, c,.tract.t,rl ira:o so(liZ im bica:,.bon<<te sc.lut:on aiid washed wlt" J. ,~}.1e ayu~:C ,i paaSl,' was aciciiizect using conc. HCl to yieid a white pre:TAite'vri;_n -,Va.ti filtercd off, v%a51!ea w'.tll K'atP,f an('~i C1rIE:,q to a"fforCl the 8i,lrtlJ..le cora~~, ~,.i:ci.07g).

WO 9S"Nia143 'f'CT/S:,98/01393 b) [3a+S-[1(E),3aa,6ct,7a(3]]-1-[3-(3,5-Dimethoxyphenyl)-1-oxo-2-propenylj-t:exahydro-8,8.-dimethyl-3H-3a,6-methano-2,1-benzisothiazole-2,2-dioxide The subtitle compound was prepared according to the method of' Exaniple 19, step (f) using the l:,rDdu:t trona step (a).
5 W5 ::06 #~~'t-;-:c:i'l Ct;:.%).

c) [.3aS-[1(1S*,2.S*),3aa,6a,7ab]]-1-[[2-(3,5-Dimethoxyphenyl)cyclopropy:]carbonylJ-hex aby d ro-8,li-dimetlay'-3H-3a,6-methano-2, I-benzisothiazole-2,2-dioxide Thc. subticle compound was prepareu according to zhe method of Example i9, step (g) 10 using the product of step (b).
MS (A.NCI) 4i8 (iVt-t1 , tUO lo) d) (h'-,i~.an., t-2-(3,5-liim,etha.ry;pher:yl)-cyclcpropane carboxylic acid The subtitle compound was prepared according to the method of Example 19, step (h) is usirlg the product of step (c).
MS 'A "Ci; 221 (M-:t{'; 101DIA) e) [1.R-twans]-2-(3,5-Dimetlhoxyphenyl)c,yclopropanamine, [R-(It*,I!*1]-2,3-.dihwrlmxvb jtanedioate (1:1) zo Th%,, :y>>TM , C,Orn7eUr. a. v- A~ ~rnpa.red according to the method of Exarnple 20, ,tel- (b) using ttie product: of step (a).
NMl:I 6H (a~-~~-iir;~!".~) 6.:32-6.31 (i'ri, m), 6.26-6.25 (2H, m), 3.92 (2H, s), 3.71 (6H, s), 2.7j-2.a=,6 r,) 2 lU- 2.O1- (!H, m.) 1.23-1.08 (2H, m).

25 f) 'L,1::i-i.1u,,?f.s.t1-4-['7-[[2-(3,5-Dinlethoxypllenyl)cyclopropyl]amino]-5-(p~'opytt:, i,~}.:~h=-1,2,:1-tr-r..~zssfo[t,S d]pyrinn~iclin- ;-yl]-cyciapeniane-1;?,3-tridl The Zit:,: c:;mpouna w-is prepared according to the method of Example 24, step (f), using the pr -.+s )t s,.f~~ :: ~ ar<<i :.xam.o-P '24, step (d) MS W-'Q:'x) ';():i (M+:q 100%) 30 NNr:t-~ 6i:1 (cti-:)mSO.i ti,315-(:.3G (3ri, tri,), 5.10 111, b3}, 5.00-4.9~ in), 4.t,'7-4.63 (1H, m), s'r, ~.7fe 3.i J (1=AA, m), 3.73 t6rI, s), :5.22-3.17 (1I., nz;, 3.01-2.64 2H, m), 2.62-2.6, m), 2.08-2.U'_: tiH, m), 1.91-'..87 (111, m), 1. 53-1.4f; (2r1, m), l.:3'-1.32 s).

Example 65 [1S=- jla.,2a,3b,.5b(1S*,2R*)'].-3-[(2-Hydroxy-2,2-dimethyl)ethoxy]-5-['!-[(2-phptuyleycior)ropyl)aniino] ==5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopent.ane -1,2-clio I.
a) 2"[[r:3aR-j3acx,(1cc(1R*,2S*),6a,6aa]1-6-[7-[1V [(2,4-DimethoxypherAyl)mei, hyl]-2-(pheinylc),ciopratlsyl)aYnkuci]"5-(propylthio)-3H-1,2,3-triazolo [4,5-d]pyrimi 3in-3-yl]-tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3,-dioxol-4-y1]oxy]-1,1.-=dimethyl-ethanol To a suiution of the product from Example 23, step (b) (1.15g) in tetrahydrofuran (25m1) at to 0 ir vas added metnylmagtt: sium bromide 0.43ml, SM soiutlon rri Tiir). i ne reaction was stirred ior i hour trlen duenched with L0% amrnonium chloride sultztion and the reactton maxture partitioned between ethyl acetate and water. The organic phase was sepaxa.ed uried and concentrated. Purification (Si02, ethyl acetate: hexan:
1.3 tl-I as eluent) afford.t,j tn.e suatitic, ,.,ompound (0.80g).
MS (APCI)'ii-5 (M-t-ti , 06 %) b) ;1.~-jla,'~'~,3h,5bj1,~*,?N*)~j-3-((7-.Hvdroxy-2.2-dimetlayl~ethoxa ~-5-i ~
[(2-phera.;vtcyOonropyb)ataainol-5-(propyltltio)-3H-7.,7,3-triazo?o l4,5-d]
pyrimidin-3-yl]-cycP or-entaiae-?.,;i-dio'.
2o The title compouiid was prepared according to the method of Exampie 2, step (b) using the pro~i.ic; of sten (a) MS rAi-~(.t~ -i0S (M-W. 101;010 NMR 6N. (db-iANiS&I 9.35 (1H. t, J-4.5Hz), 7.31-7.27 (2H, m), ~.1-7.15 ~31=I.
.r.n). 5.13 3H7), 5.05 (114. d, J=3.9Hz), 4.98 (1H, q,.1=9.0t.Iz) 4.63-4.56 (1Ti. m.), 3.94 (11., s) (i;.(, ;i, j~> i3.i-'L), s....] ;11=:, n), 2.97-2."ti:. 2.1'~(11-. 2.04 (l.H. m;, 1,5:: (L,-;:, m), ',a ~+., ni), 1.34 (Ia;i, tri;, . i:, 3 F, sy 1.09 ("H, s), 0.81 (3H, t, J=7.5Hz) Exnwp?e y'i met:~yteiliyio~.y)p~~a~yi)cycloprop! 1]aniYLOj-~"(prupYlt,uia)-:s~I 1,~,:1-tirlazJ,Ut4,5-dl~a'rit:.tzcl~,ti-3=vI' a) 1-Et4,myt-44, 1-methyletltoxy)benzene Pre.p%re;d acc:c.:dtng to te TaFti.i?od of Example '429, siq, (a) using ~-(!-rt:,e:th.jIi=ti;:+xy)-,wd~.
ben.e h WO 99/03143 PC y /,QF.98/01393 MS (EI) 162 (M+, 100 Io) h) (1,1t-trans)-2.,[4-(1.-2Vlethyletht)xy)phenyl]-cyelopropane ,: arbr,,K~'lic ai.' .1 Prepared according to the method of Example 20, step (a) the product of step (a).
N18 (APt-:1) 219 (M-11", 100%).

c) (1R-trrens)-:2-[4-(.!-Methylethoxy)phenylJ-cycl:)propanamine Prepared according to ttie method of Example 19, srep i) using the procluct cgr' step (b).
NMR br. (d6-DMSO) .GO (2H, d), 6.76 (2H, d), 4.51 (1H, sept), 2.30-2.25 (1.114, m), 1.67-io 1.61 (1H, m), 1.21 (611, ci), 0.85-0./5 (LH, rrs,).

d) [3a.R-r3.qa,4a,6a(1fl*,2S*),6aaJ-Tetrahydro-2,2-dimethyi-6-[7-[[2-[4-(1-ms:thyleth oxy)ph enyl] cyclop ropyl] amino] -5-(propylthio)-3H-1,2,3-triazolo [4,5-dagrr=rlr:.~3..'~y . ., ,.x. . .. . _ . . .,.. .. ~ ... ..
n-=,. ]
-~~:~) _ ~_'. ~.. .~ . ~ i= t!~'d'.Ia a ~~~~p), e) [~..5'-[la,2a,3~,51~(1J'*,21~*)]1-?-(Hydroxy~methyl)-5-(7-iE2-~~-tl.
rre~"~~i;Etd yNO-:~1:ahcrylJr.~;rlop-rnp~ l~~~nn~~~oJ-S-(p,~ a-~vlthin)-:~l~
1,:',3-.trix;~olo[4,5-2o t11j1-,j,r drraidnn-3-y1J- cyclopentane-1.2-diol Prvpared according to the method of Example 57, step (b) using the product of step (d).
NIv1k oti (06-DIMvv) 9.18 (lri, d), 7.11 (Lti, a), 6.83 m), 5.01-4.97 (2H, m), 4.74-4.10 l'eH, m), 4.55 ( i.H, sept), 4.46-4.39 (tii, m), 3.89-3.85 (iH., rn), ~i.:51-3.45 (2H, m), 3.14-3.0 ('_H, m), 3.321~..2.81. (2H, m), 2.30-2.20 (1H, m), 2.09-2,.06 t21-t, m',, -L.89-1.79 (LH, r2). 1.59-1.49 (1H ~~!.1, 1.47-1-.41 ('.H, m), 1 ..2d. (7H, m), O.99 r?H
t).

WO 99/05143 ?C'r/FE98101393 Example 67 [1S-[1 a,2a,3b,5b(LS*,2R*)]]-3-(3-Hydroxypropoxy)-5-[7-[(2-phenylcyclopropyl)amrnoy-5-(propylthko)-3H-1,2,3-triazolo [4,5-diJpyrimidin-3-y1]-cyclopeutar~e-~,2 dicl S
a) [3aS-[3aa,4a(1S*,2R*),6a,6aaJ]-N-[2,4-=(Dimethoxyphenyl)methyi]-3-[2,2-dimethyl-6-[[[3-(tetrahydro-2H-pyran-2-yl)oxy]propyl] oxy]-4H-cyclopent.a-1,3-dioxol-4-y1]-1V (2-phe,nylcyclopropyl)-5-(propylthio)-3H-1.,2,3-triazolo[4y5-dJ py rimictin-7-amin e.
to The suiutit-e curnl c>uncl was preparea aceordin~ to ttie niezhed o, Example 31, ! tep (d) using t.ae produ.cl: ;.ir Example 2~, st:,p (a) and 2-(3-aromopropox /)-:~'-1-'~etrah;,(iropyran.
Nts ( Ail1',I, i 7:) 1f7U%) b) [1~~-[ia,2a,31b,5b(lS*.21t*)]]-3-(3-Hydro::ypropoxy)-5-[7-[(2-15 pbenylcyclopropyi)amino]-5-(propyltnio)-3 K-1,2,3-triazoto[4,5=rl jpyrimidin-3-yl]-cvclope ntane-1,2-diol Tr?e title com.vollnri,7,a.s n erared ac:ording to the method of Example 2, step (b) using the product of step (s+.).
Mis 11 kp(:'I) 501. (Am J.00%) 20 NMR bH ((i6-hM:iO) 9.34 (1 H, d, J=4.OHz), 7.32-7.25 (2H,. m), 7.22-7.15 (3H, m), 5.11 (1I4,d. 1=33 Hz), 5 04 (?H,d, <I 3.R T-i7), A.97 (1H, q J=9.1 Hz ), 4.62-4.52 (?H, m), 4.40 (1F. ~, 5.21-iz , 3.95-:~.92 H, ITt.). 3.15-3.66 (1 I.EI, rni 3.59-3.41 (4H, m). 3.25-3.14 (1H, m), 3. 13-2. a8 (~':-f, ni), 2."iti- ,2.55 (i t1, Ie), 2.30-i 95 a"21-, mi, ('2I{, :n)., 1.57-1.28 (4* , r~-~,,;.rl ,3H. t,,1='7.5 Hz).
Elna-r,ple [1~ , ..::,.:F,:113;~,... :t,' ~ *3I(-4-[ 1-[12-(3,4-Difluorophenyl)cy6oprdpyl]ainino]-5-(prn;;7,3,rtl7i o)-3H-:i,2,3-triazolo [4,5-dj pyrimidin-3-yl]-cyclopentane-1,:'.,,3-=tMi or a) ~.;~~''-[1{1a1.:-acx,~~cc,i.~~"~]-1-~3-(:y,4-.ili~rA.~kophyu~yi)-1-oxo-2-c"ro,a~~,yli-t ,x~laydro-8,iy-~" ilrtPtlk.vi-:ia~"-3a,S-I~ f:tltranr--'l, Y-ioenZisu thia2ule-2,2-dyo~.ide Ttte sut+ti'lz cOn-.puufld. wa.s prenared. according to the method of Fxamrle 19. step (f) using 1'uc;roF;r,er,.y~)-2-prcpenuic acid.
, /y~17/Dl WO 99!0:.143 i'C't,','?9FA1393 b) [3a.5 -[1(}lS*,25'*),3aa,6a,7ab]]-1-[[2-(3,4-Aifluorophenyl)?:yclopropyl]carbonylj-hexabydro-8y$-d! i methwl-3.K-3a,6-methano-2,1-benzisothiazole-2,2-diexide The subtitle compound was prepared according to the method of Example 19, step (g) using the product of step (a).
MS (.4PC'1') 396 (:~!/1+H",100%) c) (1R-trarzs)-2-(3,4-Difluorophenyl)-cyclopropane carboxylic acid The subtitle compound was nrepared according to the methcd-of Example 19, step (h) usilz; tne; prcciuct cf siep (b).
NMR oiri (C:i;Ci3) '7.b6 (lri, dd, J=i0.0, J=u.S ML), 7.46-1.31 (2ti, m), 3.11-3.u3 (1H, m), 2.37 ( i: i,at, J=8.5, J=4.4 Hz), 2.17 (1 ti,dt, J=9.2, J=4.8 Hz), 1.86 ( i H, ddd, J=8.5, J=6.9, J 5.2 iiz).

d) (1R-trans)-2-(3,4-Laifluorophenyl)cyclopx,opanamine, (R-(R*,R*)1-2,3-dil.ydroxyinatanedioate t,i:i.) The s=ur t:.r.ie r-,rn-pcunc was -.-)r pa.rea accorciin~ to tne method n- r rxamaie 20. step (b) usin:; cne; procruet (~i s*e.,7 (r:), MS (APCI) 1"70 (M+ff,100%n) 2o e) (ld~-i 1~c,2(i,1~i,4cc(l,yS*, 2R*)jj-4-[7-[[2-(3,4-Difluorophenyl)orclopropyljaminoj-5-(propyithio)-3H-1,2,3-triazolo[4,5-dipyrimidin-3-yl]-cyclopentane-:t,2,3-tN=iol Tne ti*iP compot;nd was prepared accortiing to ttie method oi ExamulP 24, step (f) using the produr;ts of step (d;) anct F:xampie 24, step (d).
N!S 4'~9 (Yt+IAr.,1VJ,io) 1r1:, d, J.-.,..2 Ilz), 7.40-7.22 (21x, ni;, 7.10-71 0t' ('tl, m), 5.13-4.90 4.6S-4.60 (1H, nl), 3.97--3.90 (llx, m), 3.92-3.76 (V-I, m), 3.20-?.80 (3H, m), 2.62 2 S'J (1H, m), 2.L2-2.04 (1H, m), 1.96-1.83 (1H, m), 1.75-1.36 (4H, m), 0.82 (3H, t, WO 99103143 PCT;SE98/01393 Example 69 [1la-[ 1. cc,2a,3~ (1S*,2 R*),5[31]-3-[7-[[2-(3,4-Difluot*ophenyl)cycAopropyl]arniino]-5-(pro-jylthio)-3H- 1,2,3-triazolo[4,5-d]pyrimidin-3-y:]-5-(hydroxymvthyl)-cyclopentane-1,2-d.iol a) [3at't-[3ssct,4oc,6a(1R*,2S*),6aa1-6-[7-[[2=,(3,4-Difluorophenyl)cyciopropylJamino]-5-(pr,-p3,lthio)-3hd-1,2,3-triazolo [4,5-d] pyrirnidin-3-yl]-tetrahyd ro-2,2-dime .ltyl= 4H-cy t.lo p f.nta-1,3-dioxole-4-tnethanol Prepareci according to the method of Exaniple 1, step (a) using the product of E;xample 68, io step MS (APCI) 533 (M+H'', lUUulo).

b) [1.h-[Yu,2a,3R(1S*,2.R*),5[3]]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropy7ja>tnino]-5-(propylthio)-3,H-1,2,3-triazo'io [4,5-d]pyrimidin-S-yl]-5-(hydroxytuethyl)-cyc-opentane-t5 1,2-riiot Prenared a.ccording to the metnod of Example 57, step (b) using the product ot step (a).
NMR o'rl (d( -17M5O) 9.36 117i, d)., ?.39-7.2 i.27 (rn), i.10-'I.0:i (l.H, m), 5.05-4.95 (2H, rri"); 4.74-4.71 (211, m), 4.46-4,39 (? H, m), 390-3.g6 (1H, m), 3.53-3.41 (2?1. m), 3.18-3.12 ( I H, m'1, 3.00-2.81 (2H, -xa ), 2.31-2.21 (1 H, m), 2.16-2.06 (2H, m), 1.90-1.79 (1 H, m), 20 1.58-1.46 (3H, m), 1.41-1.34 (1H, m), 0.83 (3H, t).
2.R*)11-.4-[7-[[2-(3,5-Difluorophenyl)cyclopropyl]amino]-5-(pr i!rõ,I1'hirs)-tH-1,7.,3-triazolo[Q4,5-dJpyrimidin-3-y1]-cyclopentane-1,2e3-trA.oi a;, [:;~:; =[~ {L;,:sac~,(itx, i a~ ];- ~-[3-~3,5=t:~ifdut~t ophenyl)-1-oxu :2-l;r op~ uy1]-hexa',''~ydro-8,8-cl-methyl-31I 3 a,6-m ethano-2,1-benzisothiazol.e-2,2-dioxide Tn, , :.;L:. e corapcund was p:epa_r-lci accord ing to the method of Examn'e l (f) using 3-=(3,5 -:i;fn.or:,l;;.c iv,11 30 b) [1;~'~~,25'*?,?aa.6.~,7ab]J-1~-([2-(3,~i-1wi;:Xirc~ropt-enyl)~yclap~opyl~.rarbonyl]-~
TI=e ;~:J~+l'~? C:CI .pC~)i?=. w%~S pxenai-el tt=.F. ; tcthpld r.s.'?;xanlple 19, step (g) U; i e? rh,: ~l; Ctc~UC' nf' ,ti .J~ (~,) M:, W 99iDS143 ?C'T/SE98/01393 c) (1.R-trans)-2-(3,5-.Ditluorophenyl)-cyclopropane carboxylic acid The suhtitle conlpound was prepared according to the method of Example 1; , step (h) using the product of step (b).
N'I;', ' 11,.71) 197 (M-1-1+,l(S6c"'o) d) (1.R-(tran.s)]-2-(3,5-Difluorophenyl)cyclopropanamine, [R-(R*,R*))-2:,3 -dihyd:7=ox)Ic;uiaveelioate ~1:1) The s~-j:),itle compouad was prepared according to the method of Example 20, step (b) using the product of step (c).
NiVii-, vH t.db-i,iVlS(:~)'1.0ir-fi.84 (3H, zn), 3.98 (2H, s), 2.75-2.69 t'lri, r.ii, 2.i 6-2.10 (1H, m), 1.28-1.15 (2H, m).

e) [1S-[loc,2p,3(3,4cx(1S*,2R*)]]-4-[7-[[2-(3,J-Difluorophenyl)cyclopropyl]amino]-5-(pr. opyltnio)-3fi-l,Z,3-triazolor4,5-djpyrimiclin-3-ylj-cyclopentane-1,'L,s-triDl '1'he title cornpound was prepared according to the method of Example 24, step (f) using the ducts of step (r!) )nc .l4,xample 24, step (d).
1V.'' S i Fa1'CtI 4'19 ( M+H *.1 00%) . ..
N~~~:tl. t~ri (ctE-..uiVCSt.~) 9.3~ (11H, d, /=4.2 Hz), 7.01-6.95 (3H, m), 5.11-4.91 (4rI, m), 4. -2o 4.64 fFK, *r), :? 9A-:3 91 I-I m), 3.77 (1H, bs), 3.20-2.80 (3H, m), 2.55-2.55 (?.i-I, m), 2.20-2.10 (1H, m), 1.95-1.85 (1H, m), 1.63-1.43 (4I-3, m), 0.81 (3H, t,.T=7.5 Hz).

1r:~' axx~'~r le '1( [.l 2R%w )i-4-['l-[[2-j[Xsl.'-l3iphenvl]-3-y1)cyciopropyl;auiino]-5-2s (p a) kti+;a..i'-[i(E"~)-Irirt,6oc,7a~j]-l-[3-[[1,1'-Biphenyl)-3-y1]-1-oxo-2-propenyl]-hexahydro-8,S=,t]::u.ict:sye-31i' 3a,u-niethano-2,l-benzisothiazole-2,2-dioxide The s,iVtitle corn.pound wa: -irepared accordtr to ;he method ef Jtrxample 19, step (f) using l likC'ol [;11,5~',2.y;~',,laa,~.a,'"~~b])-1-([2-[[1,1'-Bipheayl)-3-y1)cycloP*oPYI]ca.rbonyl]-b) Ar3-3.c1 tIfA~22Yfi 7.1-"3ei121,>ll~hia3~}l2_"~Y ryfrnKi'.if:

(g) WO ':9 051 43 PCT/SE98.101393 MS (APrl) 436 (1V1+H+,100%) c) .2.((l.j.;'.Bi~:i tveyijF.3:,~1j cy-JolJro?F.::.nc carbac;l;.o acir:
T-i:. :ubti l.c: ~or:rpounc' was prel ared acccrding tc tl1c; mLthcd of T;camplt: 1y, s~e~, (h) uIS n,; ':}.c c r oduc;e of s:e P
MS (APCI) 237 (M-H+,10M) d) [1R-(traris)1-2-[[1,1'-Biplaenylj-3-yl]cyclopropanamine, [R-(1t*,R*)]-2,3-dihydrnxybritalneaioate (.i.:!) ro The subtitle compound was prepared according to the method of Example 20, step (b) using trify product oi step (c:).
MS (Atc'l:i) '' iU ~1V1-ti , i(xl:o) e) j1S-l lta,20,3P,4a(iS*, 2..k ")j]-4-[7-[[2-[(1,1'-Biphenyl]-3-y1)cyclopropyljamino]-5-(propylthica )=-3H1,2,3-triazolo[4,5-djpyrimidin-3-yl]-cyclopentane-1,2,3-triol T~e ri*.ie c~m.p(,unc w:ts prepared according to the metnod of Example 24, step (f) using the p.rcciuc;or of step (ct) anu Exarnple 24, step (d).
MS (~P(. :ii NMn: fiP f dF-i~;v1S ~l 93 i' l H. d, .I =4.2 Hz'. 7.70-7.18 (9H, rn). s.. l 2-4.91 (F?=H, rn), 4.67-4.64 0 R, nn?= 3.64-3 93 (1 F, m), 3.78 (1H, bs), 3.28-2.80 (3H, m)., 2.62-2.50 (l H, m), 2.25-2.1'; (1H, rn), 1.95-1.85 (1H, m), 1.59-1.41 (4H, m), 0.75 (3H, t, J 7.5 Hz).

Exs:ronMe 'T2 ,'-"y,~{:,,,-3-['7 [[d-[1,;t'-Biphenylj-3-yl]cyclol,ropyl)amin.oj-5-2s (prupyitbio)-3I<f-ls2;z-triazoln(4,5-d]layrinzidin-3-vlj-5-(hyrlroxynothyl)-~yclopentane-1.~;=r'_.~

aj r~ ~i~ (3~u,4c~,tia(1~~',:::~*),6aa]-ci-['~-[[2-[1,1'-13iphenyi]-3-y1]cyclo;~rc~1 ylj~mino)-5-(prop;i:hic; M-=:..2,3 t iu ~~cin[4,~+-~1p~ rirY,ic!in '3_~11-tetrahydrn-7.2-~limettrWl-4H-3o cYr;nl~sta-l,3==dioxole-4-P.aethanol to ~he f:t1~Y.ori ,:f &,carnp.,_- wt Y !:he r,r.a~ur;i: ef :xumple 71, WO 99/04143 PC't'/SF'98/01393 b) (llr==(1 u,2rx,3p(LR*,2S',,),5(3]]-3-[7-[[2-j1,1'-13iphenyl]-3-yl]cyclopropyllamino]-5-(p.ro pyYthio)-3H-1,2,3-tria:tolo [4,5-d] pyrimidin-3-yl]-5-(hydroxymethyt)-cyclopentane-1,2-dloi Prepared according to the method of Example 57, step (b) using the produc' of step (a).
s N1S 533 (M+H, 100%).
NMR FiH (db-DMSO) 9.35 (1H, d), 7.68 (2H. dd), 7.49-7.44 (4H, m), 7.414.33 (2H, m), 7.19 (1H, d), 6.80 (1H, dd), 5.05-4.95 (2H, m), 4.74-4.71 (2H, m), 4.46-4.39 (IH, m), 3.90-3.87 ('.H, m), 3.51-3.45 (2H, m), 3.27-3.20 (1H, m), 3.00-2.77 (2H, m), 2.30-2.17 (2H, m), 2._.2-2.04: t:t-i, ati), 1..90-1.;9 (iH, m), L.60-1.53 (ih, m), 1.50-i.41 (3t-i, in), O.'I7 (3H, t).
Example 73 N-Ethyl-i[[ l.S-I1 a,2 ji,30,4rx(YS*,zR*)] 1-Z,3-dihydtroxy-4-[7-[(2-phtr< iq c iuprolayi).iciino]-5-(propaylthio)-3;H' 1,2,3-triazolo(4,5.-d]pyrimidsn-3-yl]-cycir:rse~lt~[ joxy].-at~tam:~t~W
a) (14-~tc~, la(t.S'*,~~*)i]-1 [[4 [%-~(2 ~hen~lC~~clonrol*yl?amino]-s-ataror-~lti~io)-3H-I,:y,:3-xriaaoro~a.5 dlpyrimadin-3-41] 2-cvclopentenyl)oxyiacetic aciii Ti:~e y~ar,tstle compound was prepared according to the method of Example 2, step (b) using rbe prujuct of example 13, step (a).
MS 46" (?v,;L +.ii,lr) f:%) b) lv=E=;'iy i .2-[[[IS-(1.a,4a(.aSx,2.R *)]]-4==[7-[(2-pbenyleyclupropyl)amIna]-5 (p~=;~pyl":hio)-3F~ 1,2,3-tr:.uzolo[4.5 ~]pyrimi~lin-3-yt]-2-cyciopentenyl]oxv)-=acetamide.
3'.~: t:aI.e ' onI p or.n:i 'ca. ,;..,1) 3r:,(L ar..ardit;; to c mwt:-csi or i:U.:rly:e tu, u:;ing the Frcn,,:ct oi uep (a) ar,c: 40'16' aqueous :thylaniine.
M y:,A l"C?; 494 (M+l-1+, l00o).

c; j~-x _'~iE, N--.ti[1.C_:~:a.cz,x~i,:~~';,~c~.(iS*,2F*)]]-2,.3-clil~ydroxy-4-[7-[!2-.
plyc~k~)s~vc! p.rd~r~yll~.~r-rnt~+-5-(propylthi )-3.I1-1,t,3-triazolo[5,5-r1]~,yrimi~in-3-yl]-cyerepc:2cy:']oxyj-acetar,nide cr~ :,pc ti~i ~ a c 1-epa; e d ~.c~crc:=. ig, to ttte mpt.hod oi }:-Karap? ,-l'?, s; c-1, ; f) using thtr) ts tt-ph:;

IM:j 1 r1 a(.T )5Zo ( l~+tf , 10u%y NN=" :; ~+E' (ci6-DMS0'; 9.36 ( I)H, m), 7.75-7.68 (1H, m), 7.31-7.26 (2H, m), 7.21-7.15 (3H, n-), :3.2:;-~.}.)i (2R,1: ), 5 G:,- =1.92 (iH, rr,), ~'Y.60-4.51(1H, m.), 4.05-4.01 (1H, m), 3.93-3.78 WO 9fw/65143 PCT/SE98/01393 ")'.24-3.03 ('-'H, m), 2.98-2.90 (1r3, m), 2.87-2.79 (IH, m), 2.69-2.61 ( lH, m), 2.30-106 (2H, in), 1 72-1.4',9 (4H, m), 1.04 (3r.Y, t, J=7.1 Hz), 0.80 (3H, t, J==:'.:22 Hz).
Esxl.rp-r. 74 (1S*, 2.R*)11-4-[7-[[2-(3=-Methoxy-4-methylphenyl)cycloprops 1]ar-nino]-5-(prop},lthio)-3H=1,2,3-triazolo[4,5-d]pyrimidin-3-yl}-cyclopentane-1,2,3-trioI

a) 3-(3-lvlethoxy-4-methyipnenyt)-2-propenoic acid.
to The subtitle compound wa:~; prepared according to the method of Exampie 64, step (a) using (3-methoxy-4-methyl)benzaldehyde.
M;y .L~Nz..I' 191 b- Hexahydro-l-[3-(3-methoxy-4-methylpheqyi)-i-oxo-2-pz-openyitl-!3,$-d;methyl-3H=3a,6-methano-2,1-benzisothiazole-2,2-dioxide T4~5. su",Ltitle ';o*r.pound waW, prepared according to the mPthod of Fxam.plp 1.9, step (f) using tt:P prcn_ tict of step (2).
MS (Ai'i.;:i) 39U (iVl+rl+,liJr)'Io) c') CS i~. '}~:'u"t.l ~;::url}ri1~,, L[ 1 '3-ilh',;1etlly.l.- .~~-. ~,~,-ia.t+'ti~te(- ~s~ ~[1C;lx:,'rflt~Ii'sl/C~: <i.~-dioZide 'l 'e 5! t~t;tl: c==w,i~c l~d prepared arcordi:zg to the method cf Exarrple 19, step (g) :)rot?ucx of ster fr) rA5 40"r (hSYi~~,Y3t) v) d) si~4-to~i,as)-'-(3-Meth!:):ty-4-methylphenyl)cyclopropane carboxylic acid T~,<, su:?otlv, c.olrn~~M;u,z lwas uTepare(l according to the method of Exaniple 19, step (h) using the product of step (c).

3o lsz ey [,1:-(~runs)]-2-(3-Metboxy-4-methylphenyl)cyclopropanamine, [R-(R*,R*)]-2,3-cre~_3-d.?~,ox-,~~,utar~zdioate ~;ko.l) t; r")!',,'3J"?.,11õ c 1" :r,J C, t!"P n1Er'10o tiep (b) ,. .~~

MS (APC.:P 178 (M+H+,100%) f) 2R*)11-4-[7-112-(3-iViethoxy-4-methylphenyl) cy clopropyl] aniinci]-5-(plr- opylthio)-3h=1,2.3-tria:zolo [4,5-d] pyrimidin-3-yl]-5 cycl:,iz.rtane-1~2,3-triol 711e. ~:itie compound was p:.upared according to the method of Example 24, step (f) using th:: prcducts of step (e) and 'Ex.ample 24, step (d).
1VdS (APCI) 487 (M-.-14+,wi)%) N,wt:='ti ;PF' ;;aS.Div:':+b:j? 9 .3 L'li-;:, d, .1=4.2 Hz), 7.03 (1H, d, J--7.7 Hz), 6,77 (1H, m), 6.64 io (IH, d d., ,I-='?.7, J= l.2 Hz). 5.12-4.89 (4H, m), 4.70-4.62 (1H, m), 3.97-3.89 (1 H, m), 3.80 (3I1, s), 3.8i-3.7O (iH, m), 3.12-2.86(3ki, in), 2.64-2.53 (ifI, in), 2.iti (3H, s), 2.27-2.06 (1H, i:1)., 11.~16-i.8i(1H, 1.i3-1.27 (4h, nb), 0.82 (3H, t,.i-i.5 riz).

Example 75 [11~-[ltx,2a,3j~(Yt~*,.z5'*),5~~l-3-[7-[[2-(4-~~;1V-Dime*rwtam inoptrer.y")r.ycl.apropyl]amino ]-5-(propylthio)-31Y-1,2,3-triazolo[4,5-d~,pytriraYi dr.n-3-yi3-5- hydruxymethyl-cyclopentane-1,2-diol a) :D~metlhylaminort~benyll-l-oxo-2-propenyl]-2o bf!,K;t)iv4irr--:3,8-cairaetihyl-3hl'-3a,6-methano-2,l-benzisothiazole-2,2-dxoxide P:-enarQd acrord.ing to thP meth.od of Example 19, step (f) using (E)-3-(-'-..N,N-CitnetYkyta_rr~inophen,ya)-2-',--tr~penoyl chloride (Prepared by the method of K.Venkataraman er cil., '~ zrar ~d: on U:~tt., ;YI?, 32, 337).
1.S'y.3lol].1..[;~
1'i~:t~ ~.i~ y a;~i.:;, y;~,~rrql) l,~~r~y~y i]e~~rk~or7 i; t~~_ti:z'tzvdl o.
t~. ~.,li=~~~ tl n~u~Il wj-'L' b.e zzisaLiazoie-Z,2-c[ioxiite tO Lit, infttxodl cf Lxample 19, step (g) usic7g citc producc of step (a).
)i, =. ' 1"_r.r" , , ~ i i ~ ~-~ ,.~+ ~ C ) a..' ~a . s.., ..

c' ~1:~ p.Y~r,i --:c-(1-1'/..~~l~ir~~:thW)~+min~-~-'nFAyk~-r.yctoprn{aane, earboxylic acid Prepa::;d acccxd.ilzg :o the r,:xethod of Example 19, step (h) using the product of step (b).
h {: P U,:.',') 205 ,:M+tl' ,l'.'crN) WC 99 /t} "91. 43 PCT/SE98/01393 d) (lE':-trQn.sJ-2-(4-AIN-Dir.neth.ylamino-phenyl)cyclopropanan:iini.~, [R-(R*,R*)1-2,3-dihydroxybutanedioate (1:1) Prepared accordinn to the method of Example 20, step (b) using the product of step (c).
NMR 81F1('6-DIviSO) 6.95 (21-1, d), 6.64 (2H, d), 3.91 (2H, s), 2.84 (6H, s), 2.61-2.56 (iH, m;!,. 2.17-7.35 (1~3, ni), 1.2 1-i.14 (1H, m), 1.06-0.98 (1H, m).

e) [3aR==[3aa,4cx,6a(:LR*,2S*),6aoc]-6-[7-[[2-(4-N,N-Dimethylaminophenyl )cycYoprohli',]arnino]=-5-(proplrlthif))-3H-1.,2,'d'-tria2;cao[4,5-dtpyri:ni'din-3-yxj-tetr,Mtr;~~~lrEi-:2,z-anx me,-hyr-4f]-cyclopenx,a-1,3-dioxole-4-n.ethanor Pre:p~Lccl accorciin; to ttie rr..ctnod of _xan7ple 1, step (a) using the product of step (d).
MS (.~ '~:1) j40 (Ivk-t=,W, IOC:,L'lo ) f} 1 11,, dimethylaminophen,yl)cyclopropyij amino 1-5-(propylthio)-3H-1,2,3-triazcylo[4,5-is d]pyrim-ciin-3-yij-g-hydroxymethyt-cyclopentane-1,2-diol Pre-par:d. a,~,.;c.rclin; to trYe raet:;c)ci of rxamole t, sten i b) using tr.e n,-ociuet o', step (e).
Ma (r4dk:.1.) SOii ~Nl'+ t~',1{)t}i~l NNk 61-~ (6E-D&i;,O) 9.25 ( it-i, d), 7.04 (21i, d}, 6.67 (21y., d), 5.ili-4.v'6 (ZH, m), 4.73-4.'iOr2:1 n.), 4 46-4.41 (1ih, ni), 3.88 (IH, :;), 3.51-3.44 (2Hõ m), 3.10-2.90 (3H, m), 2.85 (6H, s), 2.?'-.2..23 (1H, m), 2.O8-2.01 (2H, r.n), 1.87-1-82 (1H, m), 1.60-1.53 (7.H, m), 1.40-1.3 %(1A, rn), l..21 i-1.1tS (11K, -,n), J.~ri t3H, t).
Example 76 mEV-f.: 'r elril3tory-t .3.mino'-5-(;)ropiylthio)-3H-1,2,3-tripzoltr '4,5--diryrimidin-3-~'t1 ._ ;'a~'d'~'~*:3'r-"'et'-yii-c, ~,.~per.iaa~ i,2-t3io:

a) 'T:>n ti!{ .;) ; ~ 7,5<x,'la~~;? A-["-(3 =, I~:cro.~4 7ncthox~phenyY)-1-oxo-2-prol enyY]-he~cak~yri.~o-)3.,fc-~limetlx=~l-:~~l-?la.,~-rserYaano-2;1-!hP~azisnfihiazo!e-','-dio~;ide Pre"p:,-.=cl :o 'kte -n~Yrk.,r,~ci ci'T~~sarrnl I.'?, ~tep (c) fiuo.o-4-W:

wp 046 A? PCT.'SE98/01393 b) (3a3-[1(1S*,2SI ),3aa,5:a,"abl]-1-[[2-(3-Fluoro-4-methoxy ~h~aayl?.:yc,~,p~upylJcar=be~~yl)-h,ea:a.hydre3-8,8-clirnethyl-3H-3a,6-ra~~eth;
benzisothiazole-2,2-dioxide s F:=epaL%:d uc(;,.)rding to tl*.e aYAet;r,od of Example 19, step (g) using th,-, product o~'step (a).
%) MS (APCI) 408 (lYi+1-1+,100 c) (1 Flv, nro-4-:nothoxJ~ tl-r.yr.loprnp:~ee carboxylic acid Prepared a4:~ording to the method of Example 19, step (h) using the product of step (b).
NIV1R SH (: I7C1;) 6.91-6.81 (SH, rn), 3.87 (3H, s), 2.58-2.51 (1H, m), 1.86-1.80 (1H, m), 1.66-1.60 (ltli, m), 1.37-1.25 (1H, m).

d;i [:l R-(.tpan: ~)1-'2-(3-Fluorc -4-methoxyphei-~,I=1)cyclopropanatnine, r1:-(R*',llx)1-2,3-dimydr)Yybutanedio ate (1:1) Prepared according to the method of Example 20, step (b) using the product of step (c).
Nhik 1 (:Sii, ra1, (31-i, s), 2.6'1-2.62 (1H, m), 2.1' '; '13 ~;, l 1' i.115 (.'riõ n11. e) [3a]t-(3aa,4cc,6a(iK*,2S*),6aa)-6-17-[[2-(3-Fluoro-4-erryl)cyclopror)yllanAinol--S-(propylthio)-3H-1,2,3-triaizlo1e i4,G=,:'Jl.~urimidin-3=.!ij- t.t:ahw ,:;.2-dairarei-,-,yi-4H-cyc:opetz~a-1,3-dioxote4-metloanoi Prepared according to tne metnod of Example 1, step (a) using the product of step (d).

MS (.A PC:() 5c 5 M +:K', lOi-*) f) me+hfyl_y pli i.ziy1)cyf 1c,prLpyl j.+-,nina1-5-(propylithio)-3H-1,2,3-triazolo [4,5-d)pyrimidin-3-y! q-5-(iiy rl roxym ettryl)-cyclopentane-1,Z-ciioi P'i"l:T- 21'C is at;,7_iL .1;; L0 lbE of '"-Xatill']t ;.. F.tt'J3 (b) US1.ll.g fhe PrCli"Ucl: t;1Y .,,!'t'p (e).

NNik 6t-I ((16-llNtS'0) 9.30 ( iR, d), 7 11-h.98 (3H, m),'.04-4.97 (' :H. m).
4.73-4.70 (2H, 3,81 ; 3H, 1-3.45 ;2D., :xi), :'..1-3.09 (1H, m., r.), '.2"2:? ; 01?-..,.06 (2H, rn), 1.9C~ 1.f13 '111, 1.57-1.47 (31i, n:), E4campie '77 j1 (1S*,2R*)11-3-(Hydroxymethyl)-5-[7-[12-(4-methoxy-3-rnethylph en 1, I)cyclopropy1; arnino?-5-(propylthio)-3FI-1,2,3-tri.azolo 14,541 pyrimidin-3-yl]-cyclopentane-1,2-diol a) ;3a.;'- [1(1;),3 aa,6a,7apj j-1-[3-(4-NlethoxFT==3-methylphenyl)-1-oxcj=-2-propenyl]-hexa.hydre-$,8-dimethyl-3H-3a,6-rnethano-2,l-benzisothiazole-2,2-dioxide Prepareci accordin; to the raethnd c>f Examplu- 19, step (f) usir.~iÃ; (E-?;-'=1-mctlioxy-3-mP:tnyAphe~~.yl)-2-proflen,~-i,'I acid.
to 1VI.S 390 ~iVl+ff',id0'7o) b) [3a..~-(i(ltS'-,2,Sx),3aa,tia,7ab]]-1-[[2-(4-Methoxy-3-n:eti~nyiphieYlyl)cyclapropyl]carbonr7l)-hexahydro-8,8-dimethyi-3H=3a,S-methano-2,1-beuzisothiasaoie-'r,z-deoxt.L"e Prepared according to the method or' Example 19, step (g) using the product of step (a).
IV1f S (A PC)', 404 (b-1-+=H ',.1 Jt)~,b ) c) ttM-transji-!-(4=!1,!Iethnx:7 -3-methylphenyl)-cyclopropane rarboa~vlic acirl Prepared according to the method of Bxample 19, step (h) using the product of step (b).
NNiR b1=: ('_'uCi1) 6.~4-6.89 (irl, m), 6.74 (lri, d), 3.81 (3H, s), 2.57-2.51 (1H, m), 2.19 (<la~, s?, ?.~: 1.'i'~ (lii, nl)1..5 -1.~r (li-f m), 1.38-3. 32 (iH, m).

di {~~-rra,r~s,+-> (4-i~!lethowy-~ mertivlp-~eo~rl)cycio~+rnpar~an inc, ! ft ~~2X.~ ~-:e-2,3-d.,,*~'!~i'11;~~1131"an~i~i~~te zs tc the me+hod of Example 20._ step (b) usinb thaYr;auct of step (c).
6.'.';.3 - '.~C- Gtj, rYi) , ii.j 3-5.30 in), 3.92 i(3H, s), 2.fN4-2.LO(_' 2.13-2 07 !4T~., m),'..2,2:-?.l6 (1H., ra), 1.08-1.01 (1H, m).

e) 4-l~let,tY~tx~T-3-m7~r ~pMl.hkrM~l~cyclc-pi ;ar+yi;s~mx~~,]._~ ti1-~~o~.vytt.:io}-:~.i~~
yl[-'tc~e':' Pr:.par_,d according tt- the rnetnod of Example 1, step (a) using the product of step (d).
Ni-', ; ( ~r~'1! 541 (?'~1+t1',10~~~i~) WO 4-9/tt"s14:- IPCT/SE98/01393 f) [IS-[1a,1,ot,.3p,5(3(1S*,2at*)~]-3-(Hydraxymefhyl)-5-[7-=[[2-=(4-methoxy-3-methylphenyl)cyclopropyl] am in o]-5-(propylthio)-3H-1,2,3-triazolo [4,5-d]
pyrimidin-3-yl]-cycl.opentane 1,~-dinl Prcp, e:a. a cor~i<..; v.~ the -nF,thod of Example 1, step (b) using the product of step (e).
Mr (ATIf'T) 501 (M+I-?{,1100 79) NMR bli (d6-DIv1a(}) 9.27 (1H, d), 7.04-6.98 (2H, in), 6.83 (11-1, d), 5.01-4.9 1 (2H, m), 4.73-4.71 (2H, rn), 4.46-4.42 (1H, m), 3.88 (1H, q), 3.75 (3H, s), 3.51-3.45 (2H, m), 3.09-3.06 (1 H, m), 3.02-2.99 (1 H, m), 2.91-2.88 (1 H, m), 2.27-2.24 (1H, m), 2.14 (3H, s), 2.13-2.6~ ~2K, .n;-. i.90-i.8i (lt-i, rr.), i.59-1.53 (2H, in), i.43-i.4i (1Fi, rn'), 1.25-1.22 (IH, m), 0.85 t3.ti, r;

Exar:n ~-e f ~
:.L.;:;~1,:yb(YD',1,2S*),5i,.]I-:3-[7-[[2-(3,4-DichlorophenyI)cycloprop,,it]au-.k:no)-5-(propylthio)-3H=1,1,3-triazolo [4,5-d] pyrimidin-3-yi]-5-(hydroxymethyl)-cyclopentane-is 1,2-dia'1 a;+ (:3a,Y-~ 1.1,~,'1,'3aoc,6cY,7a f~ j]-1-M3-(3,d-Dic.hiorophenyl)-1-oxo-2-propenyl]-laexahydro-8,8-dimeth,%1l-3N 3a.6-methano-2,l-benzisothiazole-2,2-diox4de Prepared atcoording to the method of Example 19, step (f), using (,E)-3-(3,4-di~71oz'~,n'~,~r~ t) ~'-prorenf,.r. acid.
ir.. p . I :-k-' MS (AP(II) 414 (M+W,yt.N)%) b) L~ic';rlo~-ali~.en~ljcycrapxopy!lcu.rbonyl)-hc .~;~~ j..r~, ,~,~-atmethyi f~I 3 a,t; irre~tl~anc+-?,l-;~znzisotlriazolc-2;
$-~!itx; : ~
F'repareZl ~c ; rdicig t) tiie :method rif Example 19, step (g) using xhe product of step (a).
rr. :~= t.

c) rophenyl)-cyclopropane carboxylic acid Pr,:pared a:;cording to the method of Example 19, step (h) using the product of step (b).
NiQ.!2 m). ;.20 (11-i, a), h.yt -5.)3 (17,3 , dd), (IH, m), 1.1:2!.rt,i Csla; m), (i.V. m).

d) (.t:.w-trf,.wr,~)-?-(3,4-Dirhloroplrenyl)cyclopropanamine, [R-(R*,R*)1-2,3-ddhul'.4,.~~~

WO 5'S/c,~.; 143 PCT/SE98/01393 Pr:~parcd according to the method o: Example 20, step (b) using the product of step (c).
NMR 511(d6-IIMSO) 7.53-7.51 (1H, d), 7.41-7.40 (1H, d), 7.14-7.11 (1H, dd) 3.77 (2H, s), 2.73-2.58 (1I-Ã, m), 2.16-2.1 0 (1H, m), 1.27-1.14 (2H, m).

s e) [3~,??-[?au.,4=iy~5a(1.R*,')-~S*),6aa?-6-[7-[[2-(3,4-Dichlorophenyl)r.3,clopra-i.1,1]a,pninol-te+rahydro 2,2-dim ethyl-5-(propylthio)-31f-.1,2,3-triazolo [4,5-d;~
pyrianidir--3-y1]-4H-cyclopemt.v-1,.3-dioxole-4-methanol Prc;pare:. according to the method of Example 1, step (a) using the product ot'step (d).
N1J (Al-'l:l) :)65 (NI+HA,iUO Io) io NMR ii (c,L)C13) 7.40-7.33 (2H, m), 7.20-7.01 (IH, m), 5.21-5.15 (2H, m), 4.73-4.70 (1H, m), 3.80-3.%5 (2tT, m), 3.20-3.00 (3H, m), 2.61-2.34 (4H, m), 2.21-2.09 (1H, m), 2.03-1.93 (1ki, m), 1.75-1.61 (1H, m), 1.58 (3H, s), 1.45-1.35 (2H, m), 1.28 (3H, s), 1.05-0.3.I~

15 f) [1.1't-[1a,la,3b(iIc*,2S*),Sb] i-3-[i-[[2-(3,4-Dichlorophenyl)cyelopropyl].i.anino]-5-(p. i~p~~lth: ~a+-~.r~-1,2..3-tri~zolo(4,5-rtOpy~rir-nAdi~c-3-~1]-S-(lxvdrorymexbvl)-r.~ clupentane-1.
Pr t ared acc rd_ing tc the methcc' of Example 1õ st p (b) using the product of step (e).
IVrj (At'CS) j25 (?VI+H,10U~o) 20 NIvi1'c ~H I;ciF-D'MSO; 9.38-9.36 (1H. d). 7.5527.52 (2H, m). 7.12-7.19 Ilil. dd).. 5.01-4.70 (2R, m). 4.72-4.70 (2H, m). 4.42-4.A0 (1H, r .), 3.90-3.85 (1H, m), 3.50-3.A0 (2H, m), 3.20-3.7 5OH, zn;, 3.02-2.70 (?H, 2.71-2.43 (1H, m), 2.14==2.09 (1I-1, m), 2.18-2.03 ~..;s . (1I-i, rnl, 1.z! li(4Ea., rm), 0.80 (3fl, t).
25 7f, 1.9-~Ifx,2c~,:;': .~~, ~ ~S* ::~*)y ::1-~(: :-~~,min )et[~oa.~=]-~s-[ 7 -(2-ptAen~~lF~ycioprop3~1)annino]-5-pro~yithio-,1~ f 1,2,3}-=triaizo(o[h,5-d]pyrimidin-3-,l1]-cyclopentar_e-1.2-dia).

Tc a ,-;d;:ti~j: of ':i:; pro:zuc" froin ExLx.}:le 2:: (0.50g) ir:
tet=ydrefura:i (2U:r~~;i) was added 30 Fc:tkt ~~ts ii,. Itl~~).'i'he rear.'.i.c,n was r-flirx d far I nour, -nc]Pd and mr tt-u~~;} ('zyxi.) .~.u~ed. 'I'he sc!veTit was e-.apcr_ate4 ~n,-1 rhe rvsid-E; diss,)(ved in methanol (25nr)l)/coric. hydrocnioric acid (0.50m1) then heated at reflux for 1 hour.
The solvent was evz :~oi .: ci anc', the residue pur}fir.d (HPI.C, Nova-pkz C18 co1l: znn, 0.1 % acueous tr: uor,;.~~ er:c .zc:~a rr,:;tha ,? 50:50) to give tne title cumpound (1 y3mg;.
35 MS (Al-4r85 (N 1+I-i ,10 ~T
'~n) WO 39,Yl5 14a }"MSF98/01393 NiA?; tia: %d,;-Diti1SO1 :.37 '1H, d,,I'=4.2Hz), 7.83 (3H, s), 7.29 (2H, m), 7.16 (3H, m), 4.96 (1:I. 4.5'11-4.51 (1H, m), 4.00 (iH, m), 3.66 (2H, m), 3-.u1 (1H, ni), 3.03 (2H, m), 3.01-3.92 (2H, m), 2.82 (1H, m), 2.10 (1H, m), 2.05 (1H, m), 1.55-1.44 (3H, m), 1.32 (1H, p, .1=7.t,Hz). 0.80 (3H, t, J=7.5Hz).
Ex3wrple !10 [1P-(1 ay2c.;c,3(3(l.R*,2S*),5(3)]-3-[7-[[2-(3,4-Dimethylphenyl)cyclopropyl]amino]-5-(propylthio)-3-11-5.,2,3-tria.zol0.[4,5-d]pyrimidin-3-yIJ-5-(hydroxy'methyl)-cycltapentane-1,2 =daol a) 3-(3,,4-Dirnethylphenyl)-prop-2-enoic acid Prehw.'j.d accnrcbizie to the rter.hod (Df example 64, step (a), using 3.4-d.imethyl-be,a::.,..;;E':'.', ~:.
M:I'~a.'rCl; 175 Nt-H+, 100%) b; I~rolR.unyl~-;~exahydro-8,rs- dtatrtNy:':l~d-~?a,6-tn~ f: ~ at~o-2,l-ltenaisothiazol -2,2-d.ioxide The subtitle comaound was prepared according to the method of Example 19, step (f) using the product rrom st, p (a)..
MS (APCi) i4 (h,i+i-1+, i00%).

c) 3a.y'-I f ( (,"'*,23'*),3,-.a,6ct,'7ati)j-1-[,f2-(3,4-DimPth-rlphenal)cv w1opropyl)carbonyl]-hexzihy-,.ro-8,fis= rii n tla-*Tl--3 V-3a,6-methano-2,1-benzisothiazole-2,2-rlioxide Th-.- ..i citlt co:,npound was prepared according to the method of Example ly, step (g) usi:C.n t:.7e (}ioduct of step (t,*.

d) (I,i?-"n7tnst-2-(3,4-Dimethylpheqyl)-cyclapropanecarboxylic acid Tti,: ~y~c;-:t;,. c, ~=:iT~ a7d was nrepared accordir.~g to the method of Example 19, step (h) U1s::;]c~ P.'C?dU: Ui step (c;.

e) ("iR-rra,7s)-2-(3,4-Dilnetbvlnhenyllcyclopropanamine, [R-(:K*.,R*)1-2,3-d'ah~~+rc.a:~t~;~cat~et~it~o:tt (l::ly 3s T?t': s.b*.;t:e, c}njvjr<jc: a i~ a; ?3ep'd:re3 aeccrl:ng io t;rie, method cY Exarzl ic 2(, step (b) usiiig i:,; pf;d.ac~: cf step (d).

we I?g Y; V, EC'r I5E98/01393 N?'v;R (';H (:d f,--?JWISO) 7,03= ?.01 (1H, m), 6.88 (1H, s), 6.84-6.81 (1H, m), 3.92 (2H, s), 2.:i7-2.61( l:a, m), 2. ]. 8(31-:, s), 2.16 (3H, s), 2.13-2.06 (1 H, rr. ), 1.24- i. i 7;1H, m), 1.10-1.03 (11-1, mj.

f) !':'?-fln,~ ,oc,3R(1R*92S*'i,5p)]-3-[7-[[2-(3,4-Dimethylphenyl)cycloprnF-~1'.~,.ri-,av]-5-(proprrithio)-.?1:~'-:,2,3-triazolo[4,5-d]pyrin?idin-3-yl]-5-(hydroxw-metbyl)-.cyclopentane-1,'l-diol The title compound was prepared according to the method of Example 1, step (a), using the products of step (e), followed by the method of example 1 step (b).
MS (.yP'C:11485 (1v1+1-14, tt}o%) NASviR 8H d,,-DMSO) 9.29-9.28 (1H, d), 7.04-7.01 (2H, m), 6.91-6.88 (1H, m), 5.01 (2H, m), 4.73-4 713 (2H., m), 4.43-4.41 (1H, m), 3.88-3.86 (1H, m), 3.51-3.45 (2H, rii), 3.13-3.11 m', 22.1.6 -2.21 (i.H, in), :2.26 s), 'L. i'i (2H, i.~i-1.81 f 1f1, m), i.S3-i.42 (2h, ir~), 1.'i-1.23 (1H, m), u.ts i-U.rsu (:3ii, s).

Dimethylnhenyl)cyclau+rcpy?]amino]-5-(p. ti3B=1,2,3-txiazoio[4,5-d]pyrimidin-3 yl]-cyclopentane-1,2,3-triol a) (3-.R-[3a,x=4~:,6oc(.1R*, 7S*),6ax'I)-6-1.7-[2-=[(3,4-rJ-icaaethylphenyl)cyclonrouylJamino]-5-(~rpcr_=~4~tl~~o'=?.~=:'.,",3= r=ia,~opo[~+q.i dlpy~arni~lixr-3-vl"-tc~tr~~h~~imn-r,2-ciinRethyl-4H-cy~Ic7enta.-1,:3=-dioxo1-4-o!
The stlbtitle compound was nrepared according to the method of example 1. ctep (a) using thw fnoo.ucl. z=rc=~tz7 :;xa.mpic 24-st.ep (d) and the product of example 80, step (e).

b) (1.S-[lcs,2,R,3~,4a(1S*,2R*)]]-4-[7-[[2-(3,4-Dirnethylphenyl)cyclocrop;yl]aruinoJ-S-(1''. ~j F ~.~, ; 'l~' l.,Gy:3=~:14 : 1~~R~fa,.5 l]'~?y'rlai"yililE .~
S'i"~(;~i'llOlt~f~.A~l9c :. f t....
he . .~, C;l:p.:L I13 ~'Us r:r tEe r i.l;~f . , p -:r,,," using the prudu::, of step (a).

0~2+:4 , li.+OS"c) Nr/111,. TF F,IE ..?~I;;~-; 9.2,) t,.H, d).. 7.0:3-6.87 (3H, m.), 5.091, 1H, dl, 5.02 1H,d). 4.95 (1H, d), 4.93 (Ili, d), 4.68 (1H, m), 3.93 (1H, m), 3.7'1(1H, m), 3.13 (1H,m) 3.01-2.81 (2H, m), 2.6 1 1 Y-A, ra :. ~.'~ (=~~~] ~ , ;),'~.i~i~ ,'sH, s ) :i..9i) ~; '11-~, ei'i m ) r~ i, i, 2.06 (il-i, rr l. -l.. t .~?. , , WO 1gM~14:a PCT/SE98/01393 Ea.ample 32 [1R-(ta,2a,3~,5p) ]-3-[7-(Cyclopropylamino)-5-[[4-(trifluoromethyl)phenylJthio]-3H-1,2,3-triazolo[4,5-d1 pyr. itnidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol a)_13aR-(3aa:,4rx,Ooc,6aoc))-6-;7-(Cyclopropyp:amino)-5-(propylsulf4nyl)-3Ll 1,:1,3-triazof o j 4, 55-d[ pyrimidin-3-yY)-tetrahydro-2,2-dimethyl-4H=cyclopenta-1,3-dioxole-4-methanol Pre;prirerl by ;'ie method of exa:nple 4, step (a) using the product of Fx~,;,aple,1 s:.ep (a).
to M,i (M+f-I+, 100%) b; i3aR-(3ac4,,9.oc,6(x,daa)j-6-i"i-(Cyclopropylamino)-5-[[4-=
(tr+i~~:~ :0:,_Z!tBlrhy1;1; h~enyl]Shiol-3H-1,2,3-triazolo[4,5-dlpyrimidin-3-ylj-tct=u'rrydro-2,2-diruetnyi-4#i-cti,cy.olyenta-1,3-=clioxoye-4-mefiianol Preparl-d. ry the inethod of exampie 4, step (b) using the product of step (a).
114: ; (A y'i?) ';23 (INI+'rl', 100%) c) (Cyclo~nropylamin~*)-5-[[4-(trifluoromethyl)phenyl]thio]-3F. -1,2.3-triar,elo[4,5-d[pyrimidin-3-yl1-5-(hydroxymethyl)-cyclopentane-l,2-diol Prepared by tne method ai' example i, step (b) using the product of step (b).
M~ (~ ~s.:i~ u:~;: (',~:+=~=, 1~3~~,:., NNtk =ik'i (76-Uwi ",Gl 6_23 a), i.90 121r1, d),7.70 (2H, (1), 4.95-4.90 (2H, n). 4.67-4.60 (2H. rrr), 4.32-4.30 (1E=I, m), 3.72-3.70 (1H, m), 3.32 (2H, m), 2.81-2.75 (1H, m), 2.22-2.16 (1H,, n.~, 7 Ll';-2.(k! (tf-I rn.).1.81)-1.60 (1Hf, rm),1.00-0.60 (M., in).
ExacnplZ 33 [1~7i" ,~;~ "'~~ ~l~r ~~=_:;~ t~~)~J.)_~~-[~2-(3,5-n_~{chl~rap"aenf~l}cycYopr.a~yl)amy,~oJ-S-(T r'.i ".'w~h'.,~ -3d~-~ 'v.:3-r~-'r~z~lo[t,5-~JpEri~midin-:~-=,y"]-r.vclnpQ~atan~~-i, :,,3-".r=~ol aj_~x,;.e =;lr::s}:ia~x.t~~}:,'7a~i3i-14 3-;.f,~-I)ec~lc~ophwY~y-.i-l-ox~-2-prt~~c.~~;l]-hexahydro-8,1 y+-3H 39,6-me.y,x.no-2,1 -benzisothiazole-2,2-dioxide Tsut;i_e:t.;:;;rr.pounc; was prc;~ared acccrcirg to -h;; nnetriod ofex,.crat le 19, St:,p (f) using 3-(3,',.;z:..i.,:r acid.
lFr":'~ 4[4/4?6/41? (M--H153 (100%) WO ~I!~/C~14:~ PCT/SE98/01393 b)_}3a:~-~'1('S* 2SMA,3~1 r, 5a;7a(3]]-1-[[2-(3,5-lL~ichlorophenyl)c~
~lopMopyllFarbonyl]-hea;ataydro-8,8-dienet;h3r1-3H-3a,6-methano-.2,1-benzisothiazole-2,2-dioxide The siabtitl ! compound Nvas prepared according to the method of exam -Ae 19, step (g) using the prciducr of step (a).
MS (fo.PL:') 428/G30/432 (Tv1+H+), 364 (100%) c) (1R-tr,7ns;)-2-i3,5-l)ichloropkienyl)-cyclopropanecarboxyla=2 acid The subtitle compour,d was prepared according to the method of example 19, step (h) using the pi=educ;r ozstep io i..5-1.4% (1~i, rn), l.b:i-i.;L (1r:, ni), i.69-i.95 (ih, m), 2.51-2.58 (1 i-i, ra.), 6.49 ~2ii, d, J=1.8 liz' ), I..L~ (1 rq, t, d'=1.8 t-iz) d; (11~ t;=:+,rs;-2-("3,5-Dichiorophenyl)cyclopropanamine, [R-(R*,R*)]-~,3-dihydroxybiYtanedioate (1:1) 1s The su'btitle compourd was prepared according to the methoa of example 20, step (b) using the Y iC ,11(-t ::~ Stnl, f'+
NrAk ori (dE-I-1v1SU) I. i 9-1.29 (2H, m), 2.13-2 20 ( lr(. m), 2.7 t-2.81 c.1H. m), 4.00 (2H, (Z.; t, d. ,/=1.K Hz), i.40 (1H:, t, Hz) 20 e) 11S=-[! a.?a(I.S*,2 R*)]]-4--,7-[[2-(3,5-Dichlorophenyl)cyclopropyl]amino]-5-(Pi,.oPyl.thio; --.3,H=1,,2,3-trzazolo [4,6-d=l Pyrin::.idfin-3-vl j-cyclopentane-l.,l,3-tri.ol TnF taie cnrr:p~~vr,d was prepared according to the method of example 24, sten (f) using the prodiic-.s c?t step (d) and exar.anle 24, step (d).

25 N Y;, d, J= 1.8 Hz;, 1; ~ ~' i ; :~ ,., :r.;; ~, 3 =. ';1 (:.r1, M), I=:: ~-r s;, 3.'1~} (Yl~, !~ ~), 3.? J (1H, br s), 2.:9-: .7f3 (2:I, 2.64-2.54 (1H, m), 2.17-2.10 (1H, m), 1.95-1.85 (1H, m), 1.62-1.45 (411 . 0.;; ;

30 E:t:.3zjr+.le fiw ~:wi,3(S,~~cjJ-I'J-[3-~2-[[3-f'l,?,4-'Irihylroxy-c;fclope~~tyl)..5-(l~"~;~~y".~,:zi~;- tlis~zol=ta[4,~-c~jpvrinridin-7-;~:1J~imit~ojcycl~~1""o'PY1jPh'~'nYli..
35 a) (!k-;'rure~:,,..= .r ~-s ~-1~Titrprs~f,?:l~rl)Cyr.~~lpr~73lj-c~rhan~.ar acid, : 1-rimeth~,!et~yl ester WO !.5,'O:it4?~ 12(.;V~;E98r01393 A solutior_ oI the acid from example 27 step (a) (1.72g), diphenylphosphoryl azide (2.lml) and triet:'hylarni;le (1.41Yd) in tert-butanol (15n-LI) and toluene (35m]) vv;ts heat,:~cl at 85 C for 5 hours. Wa!'er was added and the mixture was extracted with ether. The organic layers were dried, evaporated and purified (SiOh2, petrol:etner 1:1 as eluent) to give the subtitle 5 corar~ imd P-s a :;plourless solid (1.91g).
NMR 6I-I (CUC~3) 8.03 (11I, d), 7.98-7.95 (11-1., m), 7.55-7.50 (1H, m), 7.43 (1H, t), 4.83 (1H, s), 2.78-2.75 (1H, m), 2.21-2.12 (1H, m), 1.46 (9H, s), 1.29-1.23 (2H, m).

b) (Al:-+ran.;).-iv-12-(3-Arniuophenyi)cycl~.rpropyi]-carbaffiic acid, 1,1-dimethylethyl to ester A suspension of piatinum on charcoal (5%, 3'74mg) and the product from step (a) (1.90g) in ethanol (40m1) was stirred under 1.1 atmospheres pressure of hydrogen for 4 hours. The ~k.s fiicered and pr}ritied (Si02, isohexane:ether, 1:3 as elt'rerrt:) :.) g:'vL~ ta: subtitle compound (1.60g).
Is NNaR SH (C;1:iC13) 7.04 (IH, t), 6.53-6.45 (3i-'i, m), 4.81 (1H, s), 3.61.
(2,'rt, s), 2.72-2.70 (1H, m), 1.9 -1.97. (1H. m', 146 (9H, s), 1 19-1.06 (2H, m).

c) ()_R-tran.v'--N-[2-[3-[(1Vteth),lsnlforavl)anxinol-plaenwl)cyclopronyY)==carb:~~Miic acid, 1,l-riiznexfiyXethwi ester 2o A soiutioin of the r,ro(iuct from step (b) (592mg), methanesulfonyi cnloLide (0.225m1) and pyx ~:r, !(a.~~;rlli.; ii r;ich,c>romethanc was stirred ior 3 hours. Water ~lvas added and the rriixtur: extracted with dichlorozrlethane. The organic layers wAre dr.ed, evaporated and purifieci (SiU2, isohexane:ether, 1:3 as eluent) to give the subtitle compound (724mg).
NtS (~ i;,r;;t d) (i1,-(,-Amiriocycioprup-y1)phtnwij-metfialaesiuitoc4axnit,tc, 2s:3-ctiby tli.ril?.ryt,rntatxedic,a.tc (11.~ 1) A s-~~ ~:: t.;ic: :,mcuct trorn. step (722m.;) in trifluoroacetu; a.cid (,::~?!11' ; ~ stirred for 3 1}c=:~rs. so;v,.m=v/as ,e.ncveci in vacuo a::t, the residue uasitled -vrith sodiu.zl bic<T'G()rd:ltt'- cc ;iltioi2 3"c e'!tracted w1th e;:hyl ac: t;3tt. l'ile o~ganic l.yer~E we;re dried and evaporate,j. '.,'hP rc~sutting amine was dissolved in ethanol (lUml) and a solution of L-taI'['ctil:: aXl.t 1,.731g1 111 -~tililIl3: k-2'3iT:l) kv3$ adiyt,',d The SolvE;it w3s r:r.l'-veC1iY. vacLlO to giti',; the silbri.t.l~- comPculnl (867m.,;).

I~TIv1_~: d:l. td,; ;~i~~ti~ -~ i.:;l+-c~,i~i (4l'i, r.:l), 4.05 (2H, s;, 2.97 (3H, ,), 2.i4-2.70 (111, rn), :n~, ?..~>4 (.:~"t ;'el 1, (t.H, m'.

WO N/0:7143 PCT!SE98/01393 q?
e; [3aS-[3.aa,4cx('R'' , 2S'';P,6a,6aa]-N-[3-[2-[[3-(2,2-Dimethyl-6-hydroxy-tetrahydro-4H-cyclUpenta-1,3-dioxol-4-yl)-5-(propylthio)-3H-1,2,3-triazolo [4,5 -d] pya imidin-7-y1] amin.o]cyclopropyl]-ph enyt]-methanesailfonamide ThP sa:y?ititie compound was prepared according to the method of Exampl.P 1, s e.n (a) using the products of step (b) and Example 24, step (d).
MS (APCI) 576 (M+H+, 100%), f) (?iR-[1a(].,g*, ?R*),2p,3[i,4a]]-N-[3-[2-[[3-(2,3,4-:1'rihydroxy-cyclopentyl)-5-1o tpr-copyl4.hxo;- 311-~1,',3--~ri.izolo[4,5==al]pyrimidin-'1-y1]am-no]cyclopropya]kitl.enyl]-methanesulfonamide Prepared according to thz method of Example i, step (o) using the proc.uct of step (e) m.-~.
MS (AI'ti.;s) 5:36 (i~i+Fi , IU(a%), is NMR $li td,6-i7hiSU) 9.67 (1H, s), 9.34 (1H, d), 7.25 (1H, t), 7.06-6.98 (2H, m), 6.92 (1H, d), 5.11 ( I H, d), 5.04-4.98 (1 H, m), 4.94-4.91 (2H, m), 4.68-4.61 (1 H, .ai), 3.95-3.90 (1H, rr.).. 's N3-; m), '! (3 H. z,), ,.98 (3I!., s), 2.9'i-2.85 m). 2.41-2.57 (1H, ni)., ~.18-1.06 (IH, in), 111f'-l, ro). 'i.54-1.22 (4H, m), O.u:: (2i-I, 0, 20 Examr~)e 235 [1S-[1 ry,,2 (i~3 B.4a(1.S*.,2R*)]]-4-[7-[[2-(,3,4-Dimethoxyphenyl)cyclopropyl]affiino]-5-(p ropy; thi~.o) W3 U=1.2,1-triazolo i4,5-d[pyrimidin-3-yl]-eyclopentane-1,2õ3-triol a) F3aS-[1(F. ?,3act,6c.,7,a(i1]-1.-I 3..(3,4-DirnPt'hoxyphenyl)-1-oxo-2-propenv(]==hexahydro-25 8,8 c+ etlM,=;?~.'"a,u=~rethak.~a=~?,".-1~rr~zi;~~at(ria.~.o9e=1,<Z-tlaoxidT;l~: ;lt;-)tAt1f:: ';~1 T?I)na.;;u -v/as prepared ucCOrding ;:o the m.ethod cf e:k~i:I1pIL -'9, S"-p(f) USing a"]A
M:; (n;- 21,;'~~ 153 (100c,10) 30 b) phenyt)cyeft)prapycarbonyl]-hexahydro-8.g-din.leth,17l-3H-3a; 6-me:thano -2,!,-be,qzisothiazole.'.,?-rlaoXidf' t,.') t.~ i,e rlrt z"yc.ci ~. _r' Th.: a. .i.,c r;:rm;~.unr. ~=~ z.: r_e,;;~recl u~ eor:~i,~;, . uzp (g) using r' , j =
Ni0, c) f'i k-6 crtis 3_L-(3,,4-Di.nethax~vphen-,71) cyc3o propanecarboxylic aeld WO 99/051.4; PCT/SE98/01393 The subtitle c,ompound was prepared according tci the method of examnle 19.
step (h) using the prodt ct (.1 i step (b).
NMR EH. (CDC-1;.) i.:14-1.41 (iH, rn), 1.60-1.66 (1H, m), 1.83-,.38 (1H, m), 2.54-2.61 (aH, rr.j, :,.f~ 5 "3ai, ;;, 3.88 (3H, s), 6.65-6.67 (2H, m), 6.79 (1H, d, J8.7 Hz) d) (Y:"~t==;'rayY-)-2..(3,4-Di.mer:hox3.pbenyl)cycl.~*)ropa.namirAe, [.R-(R*,T+'*)]-2W3P-dihydroxybutanedioate (1:1) The subtitle compound was prepared according to the method'of example 20, step (b) using the product ot step (c).
to Niv1k dri (df;-UN1SU; 1.03-1.22 (2H, m), 2.08-2.14 (1H, rn), 2.63-2.68 (1H, rn), 3.70 (3H, s), 3.74 (3H, s), 3.91 (7R, s), 6.23 (1H, dd, J=8.1 Hz, J'=1.8 Hz), 6.70 ( iH, d, J=1.8 Hz), 6.84 (1i-1, 0., J 8.:l Hz) e) iUiuietnoxypt7enyY)cy~loy~rol-yljamino]-5-is (propyTthio)-:3B-1,2,3-triazoio[4,5-d]pyrimidin-3-ylJ-cyclopentane-1,2,3-triol The tit'e cornpound was prepared according to the method of example "1.4, step (f i using the products of mn (d) and exarnple 24, step (d).

MS 1~ j'Ar.tR r11 (c(:..t.)MSC3) 9.28 i? *1, ci, .i =4.5 Hz), 6.36 i; I;tl, d, .i=8.-'t Hz), 6.31 (1 ri, d, .i=2.1 20 Hz';, 6."10 ( l1-H, d-~,j--&4 Hz, .J'-2.1 1-iz), 5.10-4.90 (4H, m), 4.68-4.64 (1 H, m), 3.93 (1H, s), 1761,:3H, :,;, '?.74 ' ~.H, s'. 171 (3H, s), 3.13-3.10 (1H, m), 3.05-2.81 (21?:, -n), 2.65-2.55 (lTi, m), 2. i Ci-t.00 (1.1=i, m~, (iH, in), 1.56-1.27 (4H, m), 0.82 (3H, c, j='i.2 Hz).
ra~'c~~ii7iylf tF' ihfb .

25 [I:3 s1:t,.':1j, .',='t:;(?.~'' .,21~"~ll.=~?-i.'7-~[:~-(4WI/~!'~~ok;~..~., niew-iy'~-; ~ ~yt)c~ c1,~l~ropyljapnanoj.:_(ln-olayltlxio)-31'~ 1.,?..,3 yi~-c,~r.tci,~w~7.r~ra~ 3,~~:,.3-triol a,i 1".':rah ' ~;-;~ ~~-~'"_'2=-'r4- at~b:ti .nR; , ,1_ 30 n~inoJ-S-(pro~-yrthic)-3.~t=1,2,3-tri3~o1o~4,5-tl~;?yTimidin-3-yl,}-2,?,=dim~t~y_~1-4~I cycloperzta-1,3-4litixol-~l-c+l The -orapound was prepared according to the method of example 1, step (a) using tl,:: l r~ -u:=i z :, rr. exG r.:pie ''. ,:;tcp (idl and example 77, step (d).

WO 991051421 PCT/!iE98/01393 b) [1:;f1cc,2j3,3(i,.,~ia(IS*,214*)]y-4-17-[[2-(4-Methvxy-3-mek:wyr~+iu+:.~;yr)cy.::-o;~ro~p~'ijarrrirro]-5-(f,rol:,;~ Ic~iio)-3,5!! 1,2,3-ti=Lazoic~;~~,5-djpyrimidin-3-yij-cyeloperrta:re-=1,2,3-triol The citle compound was prwpared according to the method of example i, step (b) using the pr ""trct: of Stcp (a).
M.P. l 5-i:z6"C
MS (APCI) 487 (M+H+, 100%) NMR 5H (d6-DMSO' 9.28 (1H, d), 7.01-6.80 (3H, m), 5.09(1H, d), 5.01 (1H,d), 4.98 (1H, d), 4.96 (1t-4õ a), 4.66 (iH, m), 191 (111, m), 3.76 (iH., m), 3.73 (3H, s), 3.06 (1H,m) 3.01-to 2.81 (Z11, m), 2.58 (1H:, in), 2.12 (31-i, s), 2.0'1.. (1tT, m) 1.8zs (lri, m), i.~56-1.49 (2H, m,), 1.42 ; iif, rn), 1.23 (1Hi, m) 0.80 (3H, t).

1E:xa'~-.p~~r 37 [li.k-=[ Ia(1S*,2tr'*),2 p,3 (3,,1a] ]-N-[3-[2-[ [3-(2,3,4-Trihydroxy-cyclopentyl)-5-Is (propylthio)- 3H-1,2,3-triazolo[4,5-d]pyrimidin-7-yl]amino]cyclopropyl]phenyl]-aceta m r?I ta a; (J.K-i'r~rr=Fl-i~~~fr (.3-~cetanric~.oplre~;yl)cyciopropyl]-carbamic acid, 1,1-dimethylethyl esrer 20 A solution of rhe product fronn Example 84, step (b) (582mg), acetic anhydride (0.27m1) ann ;n., idin:; c'',35rrils in dichloromethane (5ml) was stirred for 18 houi-s. Water was added anr-i tbe *::;x_t?.,re was e;:trG.ctpd witil dichloromethane. ihe organic layers were dried, evaporatea and p*-r.ifie?. (3i02, isohexarAe:acetone, 2:1 as e.(uent) til gdve )~.e :,u~title c.ornpou.ic.
25 Di1,13 (A.'CI;i :z25 ;;11A'.+.~070) b j k15-trar;.s;-<';, .-=~-[(2-Arninocy'clopropy I);pherryl]..aceitamide, (I1--r)i*,R*)]--2,3-di~~,;~t~nz:;~~fu~a~~~dioate A~.o:tution cr, *r~! pridur.' +rnm ~tep (a) (703rnC) in trifluoroacetic acid ;:iml) was stirred for 30 3 hours. I-he sclvent %xas r:.moved in vacuo and the residue basified with sodinm bi: ~rb~, a1:e solucron theri etJracted with ethyl acetate. 'T'he orga.alc lavers wert dried and evapcrated. 'l.ie aiiiinL was dissolved iri ethanol(10 rAl) and a solut;.ori of L-ta:-taric acid (349r .~'' t]7 Pr?'~c~r,Cl :-) rXl'~' wit5 ada't;!~. ry?P. S 1~\ E',llt w3S
r~L 1(3L'E;~ i?'2 1v,:1!13 -z0 ?iVtthe susiid~ -,ocrrpcun:l (8Z3rng).
35 NMRhri r.i;, 6,6:2 P. d.,, 4.0 (2H, s), l.; )-2.7: (IH, m), i. ~~-:%.'-.'. i t-;, m;, ~.~~a ('_,~}, ;1 1.39= l.'il (Ix-I, r.nl, 1' 8-l .08 (1F1, m), WO 09!05143 PCT/SE98/01393 c) [3a.5-[3ao.,4c4(1R*,2S*),6cc,6aoc]-N-[3-[2-j[3-(2,2-Dimethyl-6-hydroxy-tetr=ahydro-4l=t'-,cyclol.-~ty;nt a-1.,3-dioxol-4-yl)-5-(prop,ylthio)-3i7-1,2,3-triazolo [4,5-c1]pyrimidin-7-yl] ami,no] cyclop ropyl] phenyl]-acetamide s PrePared according to the method of Example 12, step (e) using the procluct of step (b).
d) !,_~'-[I.r'c"iaS''.;lR'~),7,a,.3~,4a]]-N-[3-[2-[[3-('2,3,4-Trihydroxy-cyclopentyl)-5-(propylthio)- H-1,2,3-triazolo[4,5=4]pyrimidin-7-yl]amino]cyclopr.=npyl]phenyl]-acetamide io Prf;parec: accorai,x; to ~ne rnethod ofExarr,plc 1, step (b) using the product oi step (c).
m.p. i4;

1V1.5 (L1tr'l.I) J00 101J"/6;, i'Ih:R 3 :k'd.,;-lliViSU) 9.87 (IH, s), 9.35 (1l-1, d), 7.41-7.34 (2H, m), 7.Ii, (1E1, t;, 6.34 (1H, d), 5.4.9' (41:, in), 4.66-4.61 (1H, m), 3.935-3.91 (1lEi, m), 3.82-3.75 (1H, :r), 3.23-2.78 15 (411, 6 .2.:)- (iI-i, ri), 2,.1 _/-2.08 (IH, rn;, 2.02 (3H, s),. 1.5 -)" -I.8 5 1H, rn), 1.72-1.61 (1H, r~r), l.:i l -.09 (:3r1, m), 0.86 (3lE1, t).

Exarnbple R#t [".,5'-[1rf 2~3 .: 5 t3,4p.(1S*.2R*)]14-i7-~[(2-(3,4-Dichlorophenyl)cyclopropyl]amino]-5-20 (propylthic)-3L?=1,23-triazabo[4,5-d] pyrimidin-3-y1]-cyclopentane-'1,2,3-trioI

z.) 13-n-Y-13'rxeta. 6-f'(1R*,2.S*1.6ac;;1-6-[7-[2-1(:3,4-Dach'iorophenyl)cycloprnpyl]amino]-5-(pr~1T}=i'#~r )-:~'I-1,:~,3-~=ria.znlfll~,5 d)v~yrir+zl~lir,-3-y1[-te~tr~.ihy~3ro-Z.:~-~I?trnethyl-4H-c,ycloPenta-1,3-dioxol-4-ol 25 ':'he wvae n-ji:se;+l acc.orrl.ing tn *he :r.et:icA of .E:;:~rr ~,le ; (a) using the. pr; 24, step (d) zn:. Example 7118, step (d).
';

b) 1S-[1cc,213.34c.~(lS*,?R*)] '-4-[''-[[(2-(3,e -Diclhlorophenyl)cyclolsropyl]amino]-5-30 (n. vi y%1i1:i i,2,'~,..t~r.rz~~i.~j.4,~ ,:34=1o7 t : :'ri.. m~,:t;;rj O':_ EK a.iirr.e s, step (o)' us:t-.b tiic .9tep (a).
n:.p. .-rJ-2C.
ML; ( r~ .yc: ?~ 11 ~a y1+Hi , 1~1(;t1o;,, Nir:Yk oi! 9.4 (1~, Ai),'7.54=1.5(-(<y'rl. rn), 7.I3 (1H, dd.), 5.13-4.91 (4H, m), 35 4.68-4.60 !l'z-:, r1). ::.54-3.90 i" zi, ?n;, 3.78-3 75 (114, ;n), 3 18-3 02 ( IH, rr.), 191-2.76 (2H., 2.:52-::.'>1 (1H, rn), 2.17-2.06 ti1H, :n), 1.94-1.84 (1H, zn), 1õ7Z-=1_.37 IH, m), 0.79 (3H, t) Example 89 5 [1S l.c,, 7;i,,a~3,4fc.(1.S'*,2R*)])-4-[7-[[2-(4-Chloro-3-nitethylphenyi)c3,cS~-arc~bl?:Linino]-5-(propylthio)-3.Ff-1,2.,3-triazolo[4,5-d']pyritnidin-3-yl]-cyclopentane-1,2,3-triol a) 3-(4-Chii~u ro-3-r.nethylpheny9i-2-propenoic acid.

io The s+sbtitle.; eoinpound was prepared ac;eorciing to the inethod of Exar.zple 64, step (a) using (4-chloro-3-methyl)benzaldehyde (prepared according to W(--) 9603387).
MS (Arc:r:) 3 91 (&1-11' ,100%) b) 3a:i-(lx*),3au,6uc,'7a[i]i-ii-[3-(4-Cnloro-3-methylphenyl)-Y-oxo-i-propenyij-is hea:ah-t;-.dre~-8iE-d'.;-neth yl-.3Fi'=3a,6-enethano-2,:l-bcnzisothiazole..2,2-ciroxid.e Tl;e snbti:i(; o:~ao'.axnv vias pr.cg;ar c.. acc;r.)rdir~g -.o ene methe:.~ of Exarnplr 19, ctcp (f) using the product: of step (a).
MS (A!'i::I) '392 (M=tl ,1GG~o) [3a~'-;1(:':~ * 23,r~,$a~.,6t=,'Ia+~;]-1-~[2..(4 ~ ihlorn-3-methylph~~rryl~
20 c) cycloproaylJca:~l~esr.y?] hexahy~ire -3,13-dimet'iiyl-31I-3a,6-methano-1,?~-benzisothiazole-2,2-dioxide Tn- s- o, ti't. t (,orr.p(lur.d was prepar d according to ttie methoci of Example 19, step (g) using th-- p:;dcc. õ~ siep lkb).
25 NMR iir: (C:UO,) '7.22 (1:-1, d,.1=8.?. Hz), 7.(?7 0 H, d. J=1.9 Hz). 6.96 i;lH, dd .1-8.1, J=2.1 tiz), 3 92 () H, dd, .I 7.5, J=5.0 Hz), 3.51 (1 H, d, J=13.8 Hz). 3.M ( l.H, d, J=13.8 H: , f?. s), 2.57-2.a7 !2H, m), 2.20-2.02 (2H, m), 1.98-1.82 (3H, m), 1.79-1.73 (1H, ni), (31i, ~ ~.

30 d) (1>1-tr~.~,,) nhorc-3-r<aethvlnben,yl)cy'cbparopancca.rl,nacylic. areicl ('.'.}) MPt.h(1r (.q) using tnF Y.7orI'0rr. Gi step (c').

NMR upi (ca~C13) '7.24 (1t-:, d, J-=8.3 Hz), 6.97 (lH, ;1, .,T 1,5 Hz), 6.fi6 ;iH, c.:l, J--8.1, 35 kz ), 2.14 r":3N, s). 1 S-6(1 H, crdd, J=9.2, WO 99/05143 PC1'/S1E98101393 J=3.2, J=4.2 Hz 1.65 (ll'it dt, J--9.2, J 4.8 I-iz ), 1.37 (IH, ddd,.i-L
1.:'.;, J=6.7, J=4.8 Hz -)=

e) (1P-tr=an:;)-2-(4-Chloro-:3-rnethylphenyl)cyclopropanamine, [R.-(R",R*)1-2,3-dxhydroxMk,utanedioate (1:1) The suhci.:lv cr~mpou:~d ~~vas prepared accs~rdi:-~;~ to the method of Exa:~~:ple 20, step (b) usini~ i:ize produc:,, ;rf stt.:p (d).
MS (<~-;?(.".1; ', 8'?!i~;4 (i1ilt+t~), 182 (100%) io f) [l.S-[lot,2(~,3~3,4cx(1S*, 2R*)1]-4-17-([2-(4-Chloro-3-methylpherayl) cyclop ropyl; anlA:o)-5-(propylthio)-3H-1,2,3=-tG: iazolo[4,5-a1 pyritrF:.cl:in-3-yli-cyc:lopentanc-1;293-triol 1 he title compound ti-vas prepared according to rhe method of ExarnpJe 24, step (f) using the l,rcducts of ste ) ~e) and Example 24, step (d).
hrtI-: 4Y.1493 (~A+t1.+), 49: (100%) NMR cSH (d6-DMSO) 9.35 (1H, d, .1=3.9 Hz), 7.30 (1H, d, J=8.1 Hz), 7.22 (1H, d, J=2.1 Hz), 7.04 { i.fi. dd, .1=2.1 Hz), 5.11 (iH, ca, ,i=4.2 Iiz), 5.01(111, d, J=6.6 Hz), 4.95 t!v, 4.9~'. (iri, d...1=4.21 i xl, 4 60-4.64 (11E1, 'lY rn), 3.81-3.75 (7?l, ~n-, a'.;'r-2. ~y (':iii rn), 2.62-2.50 (1H, m), 2.31 (3H, s), 2.26-2.03 (1H, rri), 1.97-1.83 (11-1:, m) 1.7i-1 33 (~H, m), 0.80 (3H. t,,1=7..5 Hz), Exanlr,ic '41 [ i.~=Ei cL,l j~,.3;~yb~a(tran~); i- a~-17-i t2 .(i'heuyince, ihyl)cycioprop~~~] ~~m1is u ~-5- tpropylthio)-3~1!==1 "1,3-trr~z.~4r'r~.5r'~p5'r~mi~nr :3 yl) cya~Peart~ne-1,2,.3-trlr?ii)~t.*A~d.s6-.,-!k'~e.~rYr~c:~uy:) cycxopy-Wpaazca:boacylic %ckd nJ ccirdi.rg c) -,.:e r.zethod of Example 20, step (a) using 2-(F' ~e;ri.~~~rr;,~,~.,~ s~:~~~.~o~~zo~-~r_e;cart~oxy ~.it ac:ia, (:t_hyl ,~Ster.
Q" , ' 1 Ot ~a}

1~)~tr~zf~sJ-,~;= (~-Pti{:nyl~n~~?l~yl) ~y~:lolnrog~a~na~m~ine F'repa~cecn r~c,:Y,rcJr,~~ ~z~ tne actnc,i. fji' f;xzrnp''.e: i ;, ,,,a:p tising ttr~:. 1::-o,'.ucx f.ren7 step (a).
N? 11]R SlI '.~t: 'i.55 H.. d , 2.3? =:~:. 13 ".1?. I r 1..G- 96 (1H, m), 0.03-1 ',:;4 :. 11, r: ,; da 4. , I, [1't, ir;.

cl[IS=rla,2!3,3p,,4,rx(xrans)j].4..[=7-[[2.-(Phenylmethyr)cyclopropyl]a. m:
ano]-5=.
(F-ropy;i-;.h"o) =~" 171,2VU -trY:azo1c ~-li~+.; " v:2,3=-V ic l Prt;pa~ rd to i;.;.e, r,:ethod of Example 24, step (f) using the product from step (b) and the product from Example 24, step (d).
N.1rtR. fiH (d(,-BN,iSO) 9.10-9.08 (1H, m), 7.35-7.27 (4H, m), 7.21-7.17 (]N, m), 5.11-5.10 (lH, m), 5 03-5.01 (1H, rn), 4.97-4.91 (2H, m), 4.69-4.64 (1H, m), 3.94 (1H, s), 3.79 (1H, s), 3.20-3,06 (.3H, in),. 2.78-2.76 (1H, m), 2.60-2.52 (2H, m), 1.97-1.92 (1H, rn). 1.76-1.66 (2H, m), 1.37-1.32 ('iH, m), 0.99 (311, t), 0.78-0.76 (1H, m).
Ni5 (APl'::i/ 43; (Ivi+H, itl0%) Examipie 91 [1K-(1a,2c~c,3~~(IIt*,ZS*),5~3]]-3-[7-( 12-(4-Chloro-3-methylphenyl)cyclopropyl]amino]-5-tp: sr-yl,-hao)-3H-1,2y3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyY)=
cy cloptntaYg e-t,Z-diol kk,.:25*'A, 6j(x?-6-('/- I. [2-(.4-Ch I-1 Mo-3-methv!~hr,nyl)c~7~lep~~r-ylla~.~ne]-5 =(nrnpr~lthio)-3H-1,2,3-trx.~zol a-4.5-d1 rn=*imidin-3-yll--es t=;~h~,<~r s. .", 7 -flit Fethyl..4A':-c;yc.nfsonka-=1,3-eioxc?.e-4-methanol Prepar..~tcl a:.cording to the rnethod of Example 1, step (a) using the product of example 89, ster, e;.
MI~, (fr.l''C.i 44.5, 547 I,M+r.':, 545 ()00/.')).

b) [lR-T1rx,''.sx,3p(lP*,2S*),5p])-3--I7-tf.2-(4-CTMnlaro-3-~.):~~;~~=):..;;;~~~,~~, >~--~~~~..:~:.~?~3- ~~.iolu[4~5=~iY~Yrimidin-3-2s 'Lo 'Lite r;1ei.Ilild U1'.LXaII2pIe 1, step (b) using the product o: stt;p (a).
I<1y tf1.PC;.,1 4112:i '~'"/ ("r.'.i -j#:. ~U~ ~ 4~'~~~i).
NNA::. ;iii 9.33 (.H. d), 7.31-7.02 (3H. ir.), 5.00 ;IH, q). 4.4; {1H. j 3 89-3.86 ( a-T, nil).. 3.:i ;-3.42 (2Ii, m), 3.16-3. i 2(1 H, m), 2.98-2.82 (214, m), 2.31 (3H, s), 2.27-3o 2.20 ( i H, ra), 2.10-2.06 (2H, m), 1.89-' .79 ( i H, m), 1.54-1.45 (3H, m), 1.37.-1.3 1(1 H, m), 0.V ('1-l, t).

lE~cazn~-le 97 35 ('a t t)rIig-'.ttilu)-:% A' '.,2,3-tr :az--lcj4,5-rIl'py,rinika3:ii-3-ylj-cyclt~perY:ane- ~~.,',3-triol WO 99/05143 PCT/,QE98/01393 a) (1R-trcarrso--N-j2-(3-Dimethylamin phenyl)cyclopropyll-carbamic acid, 1,1-dimethyieahyl es8er A n-u,ti; re of th: ?Jroduc ot Exainple, S4, step (b) (520mg), 3'1~'I'o aq, for,zalde3lvd.e (0.47n:1), acetic acid (Q.;rri) and sodium triacetoxyborohydride (2.26g) in 1,2-s dir,h1er,rthane (1Om1) was stirred for 3.5 hours. Sodium bicarbonate soL=-,ticn 1v,,).F a1ded and the mixture was extracted with d.ichlorom.-thane. The organic layers were dried, evaporaced arici purified (Si(:12, petrol:ethe., i:l as eluent) tc give the subtitle compound (431mg).
NMR SH k'<:DC13) 7. t3 (iH, t), 6.56 (ilf, dd), 6.43-6.46 (2r-I, m), 4.80 (iii, s), 3.92 (6H, s), 2."iy-2 %ti (li-i, rn), 2.02-1.96 (1H, rn), 1.46 (9H, s). 1.21-1.09 (2H.
m).

b) (iR-trates)-2-(3-tli.methytamino)cyclopropanamine A solution of the product from step (a) (417mg) in tritluoroacetic acid (3m1) was stirred for 3 hours. Th.e solvent was removed in vacuo, ttie residue basified with sodium bicarbonate solution and extracted with ethyl acetate. The organic layers were drie;c., evaporatedand purified (SiC?,, dich)crornethe.ne:ethanol:azn,mon.ia, 150:8:1 as elu,ent) to giv the subtitle compour,cd ("a 08vnn).
Ny.iR. iiki 2 i ir', t), 6.551H, dd), 6.46--6.44 0 H, o.i.~ iH, dd). 2.93 (6H, s), 1.60-2.52. (1.H, rn).. 1.36-1.80 (11 ~, nn), 1.72 (2H, s), 1 04-0.94 (2H, m) c) i3a~-f Dimet6a~~az.a~a;r or~henvI)s;;~clopropyll anninr~l-5-(~roiaylthic~)-3~
1.,;2.:~-triazc:~io(4,5-dJpwrirr. idin==3-yr)-cyclopentau-1,3-dioxol-4-ol PrF.:parE.rl tU (I'; aslnl; ri e;.'. Au;,t nt step (b).
(P.~~'(::) 6 ,ilo 't-Hi', 100%) d) Dnrna,-b;'14w:kitiptienyy)cl:clop"-opy:lami=aarl--s-(l3rop,ylthia)-W-1,2,3-ta=iaz~.1, i-d1l;yrt,nri:Y7i-..;-y;I -ryelcap~t~4a~~Ã 3-rricil Pre,pared according to the method of Example 1, step (h) using the product of step (c).
M.P. i.S (Ar~,f 'C; rt-Y3 "Nl=+-r,, NMR 81-1 (d;-D'11S(a) 9.29-9.25 (?.T-T, m), 7.07 (1 ]", dd). 6.55-6.52 ~2H, m), 6.64 (1H, d), 5.1U (iti, I.i'), 4.96-4.~2 (lli, iii'), 4.93 (1H, d), 4.68-4.62 (1H, m), 3.94-Wp 99/0.5143 t'CT/SE98/01393 3.5 1 (l~:i, , :3.79.-3.75 (1'3, m), 3.25-2.92 (2H, m), 2.87 (6H, s), 2.62-2,.53 (1H, m), 2.10-2.03 (1I-1, n).), 1.96-1.88 (1H, m), 1.53-1.25 (4H, rz), ,0.82 (3H, t).

Example 93 s [1F-r' ~,2r5 3~i 4t (iS'*,Zl~'')j]-4--[7-[[2-(3-Fluoro-4-methoaryphenyl)cyclopropyl]aminol-5-(prr, pylthio)-3H-1,2,3-triazolo [4,5-d]pyrimidin-3-v1)-cy,--lcpent-ane-1,2,3-t,iol a) [3ak-t3a(,,4a,tia(lR*,2S;'),6aajl-6-[7-[[z-(s-FIuoro-4-meti,nxyphenyl)-cyclopropyl]amino]-5-(prapyltheo)-3H=1,%,3-triazofo[4,5-d]pyrimidin-3-yl]-tetrahyd ro-2<2-d rmethyl-4H=cyclopentan-l,:3-d ioxol-4-ol The subtici- compound was prepared according to the method of Example 1, step (a) using the pr;;::;uc ts cf t:xar.Ipi:e <<~ , st e-p ;cl) a,-id Exarrlplc 15, step (d).
MS (AP::I/ 531~~~i~ iG0111.) b) (1S-~'.a. 2~,,3p,4cx(15'*,'.4t*)]]-4-[7-[[2-13-Fluoro-4-methoxvpi*enyll-cy~:: oprr~py- j a m w.no]- ~-=(prepylthio)-,3H-1_, Z..3-triazo!o[~5,5-.~'J
pyrianidin-3-a~1 ]-cyckopen cane-1,1,,3-triol Preparen c.r;= crdir.g to ttie methucl of Example 1, step (b) using the product of step (a).
m.,j.
MS (AYC;C) 491 (M+H', t(Wb}
NMR FiH (d6-DNiSQ) 41.32 (1H, d), 7.10-6.94 (3H, m), 5.11 (1H, d), 5.03 (1H, d), 4.93 (1H, d), 4.90 (1H, d), 4.69-4.63 (1H, m), 3.96-3.90 (1H, m), 3.81 (3H, s), 3.79-3.75 (1H, m), 't':2 '21-3. i.z;, 2.53 -2-54 (IH, 10-'%.C:j (:H, :n'), 1.96-1.87 (11=1, In; 1 (3r-:, :,r'), r:--l-..2;, (1N, ::i. 311 r).

[~ ': ~ "?~. ~I~,=':~;1~~ ~1:*)]~_,rl_[7..r~?-(3:~-~1i-1yPth~flp}~enyl)cycloprEaly1]aLx~.ino]-5-(F:,~p:+'I~-iI~~; .3.T1-M,?,'= rr ;~r.:w[~-,:i-d~pyri~r,+l~:iu-3-y1]-cyclop~inta~~ :-,~;,3-tAio-a) :s-(3a5-Te:r.?.e'h.y~pTnPMvI',-m*=op-'l.-Eaaic acid NE';31iIuj ii.-CC~'t(lI'~~ tG cI?e oI LJ'.3B'1T tL St6',p (dl,'alsIr.b, rI_c~d1v?l.
MS (A1'~. t;~~5 I Zrlqr) *rB

b) [3aS.=[1(E),3act,,6ct,7a(3j]-1-[:1-(3,5-Dime-thylpheny])-1-oxo-2-propenylj-hexahydro-8,8-cli,uleth.yl-3.U-3a.,6-methano-2,1-benzisothiazole-2,2-dioxide The subtitle compound was prepared according to the method of Example 19, step (f) using the product frcw seep (a;.
MS (.6pCy: 374 ",1+1-r' l009b).

c) j3aS'-I1(1SX,2S*),3aa,6c4'1a[i]j-1-[[2-(3,5-Dimethylphenyl)cyclopropyljcarbonyl]-hexahydro-R;B-dimrthyl-3H-3a,6-methano-:y,l-benzisothiaiole-2,2-dioxide The; suot;ltlc corn.pound was p:-epared according to the methoci of Example 19, step (g) usang tr.e produo, of step (b).
MS (AE'C1 ~ %ft~ (M-H', 100%) d) (1IZ-trarrs)-2-(3,5-Dimeth,ylphenyl)-cycle,propanecarboxylic acid The, subtitie compound was prepared according to the method of Exainpie 19, step (h) usi;:g tae pmau:7~ oT ,tel) (c-).
MS (A P(-1I') 129 rI"'i-FT+, 100%'~

e) t :(R-r.,raix. )-;;-(3.S-Y)i~metny,lphenyl)cyclopiropanamine, [R-(R*,R*)]-2,3-1'h-- sv'Sritie =:)mpour.cl was, l;r.epv-eri r,ccordiii; to th~ method of Example 20. step (b) usang the nrodiics of stpp (d.).
Mlrt iiH iu6-L1,160', t;. 5*U (,r-i, s), 6.iU ;211, s), ~.9J (2K, s), 2.66-2.6 ~ (1H, ..Y)', 2.06-1.99 si, mr, '.;.-1.04(IL 1-t,in).

1) -4-['1-([2-(3,5-13imethytphenyl)c;vclol.,,ropyllamino]-5-(pi~;F; I,2,:,-triazoio[4,5-djpyrimidin-3-yl]-cyclopentane-1,2,3-t;,=~ot The t;tie cornpounct was orPpa:Pd a.ccordi.nc- to the method of Example 24, step (fl using tN fr::ducts of .s:.e.p ;e; ana :;x,anqlj stej) (d).
1'k"
NA7i2 cf~: 'n, _. - ~1S"~l 9.31 !? H, d), 6.81 (3H, s), 5.12-5.11 (1h. m).
5.04-5.o0 ( l h, m), 4.31-4.7? i:L, ..;, -4.6 7-4.03 (llri, m.), 3.93-3.-)2 (111, m), 3.78-3.76 (IH, m), 3.21-3.14 (l.tl, ra', 0 ?E (211. m'. 2.60-2.5" (i.H. m)., 2.24 (6H, s), 2.05-2.03 '111, m), 1.92-1.91 .wJ2-1.27 (2l-i, m), 0.83 (3H, t).

lOt Exampie '3:;
[1S-[1a,2p,?, [3,4a(1S*,2R *)]]-4-[7-[[2-(3-Chloro-4-methoxyr~hrsn),Y)c,yclop ropyll amino]-5-(propylthio)-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-ylj-c4rclep ~rrr.ane-1,2,?i-t1 iol s a) 3-(3-Clilorri-4~-methoxyp.4enyl)-prop-2--,raoic acid Preparec: according to the method of Example 64, step (a), using 3-chloro-4-methoxy-be<nzaldehyde lvivix 5'ri,u~-DMSQ) 7.83 (IH, d), 7.68-7.64 (1H, m), 7.55-7.49 (1H, m), 7.19-7.17 (1H, m), 6.50-6.46 (1k-!, d), 3.90 011, s).

b) [3aS-~ i ;r ),:9atcy;5cx;, /~t j ; l-1.-=(3-(3-Chloro-4-ynethoxyphenyl)-.1-oxo-.2.-prat enyl]-hexabydro-8,8A i.nlethyl-3H-3a,6-methano-2,l-benzisothiazole-2,2-di ox'rde The subtit:.e con-ipouna was prepared accordir:~; to tne metl-iod of Exa7npie 19, step (f) using the product from step (a).
M,,-,* (A.P(;''3 408 (M-H+ 100%).

c) 43aS-[1(1,~,'*.3;5'*),3aa,6rz,7a~)f-1-[[2-(3-Chloro-4-methoxyro)hei+y11K:,vc'upro~-yllcarbonyl]-hexahydro-8,8-dimethyl-31~ 3a,6-methano-2,1-2o benzisot.hrazote-2,2-dioxide The sabrit ? ccrnr}ourtc vas ;)re~pax:ci. accardinR to t.ne method of Exampte 19, step (g) using thF, procluct or step (h) MS (Ap'(.'.) } '~ 4 (1v1-;-ff", 100%) d) (1R-trar:s)-2 iI-!C;'hlor,rs-,1-r;cEthoa:yphe,nyl)==c;lrc[opropanecarboxytic acid The subti.i~ --o..ipc;a:id was prei,~.red accord<.Zg t_o til. niethod c-f Exarryk; 19õ step (h) us:n,g Nlvtl'< ("'Iy ECDt:l,.i "I. ts (ii, d), 7.02-6.99 (1H, n,,), 6.85 (tH, d). 188 (~H, ,'.

e; (1R-I!-i-.,';..-(vF-Chlero-,l-r3ethoxyphenyl)cyclopropanamine, [R-(R*,R*)1-2,3-dil".yd;oxy,)ai;triedioate (:.,1) Th .v tl::, L:t::.znl;ie 2C, step (b) usiug ,.u 3 10 (1H, m), 7.09-7.05 (2H, m), 3.91. (2I-1!., s). 7.66-2.61 (1H, rii;, '1Tj, rr.', 1.11.) .1..55 (2P , ~) *rB

WO 99/05143 YC7C,'SE98/01393 f) [1S-[1cx,2 0,3(3,4ci(1S*s2R*)]]-4-[7-[[2-(3-Chloro-4-methoxypheny1)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo [4,5-d1 pyrimidin-3-y'.]-c.yr.Io i)e,-~Nao ~~-1,2,3-triyc The title cc:rnpo,lnE:P , a.s prepired according to the method of Example 24, step (f) using s the proiazr,t,;; cf ;itep (e) an(i Exainple 24., step (d).
MS (APCI) 5:;5 (iY1-1-1+,10C,>'~) NtvfR 51:: (?;.C"NiSO) 9.33 (lh, d), 7.32-7.31 (11-1, in), 7.14-7.112 (114-., m), 7,('7-7.05 (1H, m), 5.17-:I.15 (1 H, m).. 5.05-5.04 (1H, m), 4.94-4.93 (2H, m), 4.56-4.64 (1 H, m), 3.94-3.93 (1H, m), {.tSS Ml., s1, 3.8u ('31-1, s), 3.29-3.27 ni), 3.12-2.78 (2H, m_), 2.63-2.53 (1H, io m), 2.09-2.04 (Iii, m;, 1.95-i.88 (IH, m), i.56-1.46 (2H, m), 1.3e-i.29 (1H, rrl)', 0.84-0.81 (3'ri, t).

Exo.mple S_ti [1R-[l a,2u,3~(lR-,2Sk),Sp.1J-3-[7-[[2-(3-CVlc ro-4-is metiooxypne;oyi)cyciopropyijaminoj-5-(propylthio)-3H-1,2,3-triazolo[4,5-djpyrimidin-3-r~!.J-S-!k~,y 3~ox;yna.Pt~y~)-c~'~'lop~:ntane-l,?-d*Qi a)13aR-(7-~afc.4c~,6tx;(l..i*'?' , 2,V* ),6a(x]-6-[7-[[x-(3-Chloro-4-meth os~~p~ err~r i)PN,clopro}*yl.] gmino]-.5-(propylthio)-3H-1,2,3-triazoln [4,5-d] pyrimidin-20 3 yl]-=tetrahyd rc+7,2-dime1tryl-4.H-eyelol-enta-1,3-dioxole-4-methanol.
PrPpa*ed ar cr,.,!irT t~ tbe ~,~ thod of Exaniple 1, step (a) using the prad-:ict of example 95, step (e; .
MS (A.1-'C [) ~61r563 (M+H+;t, S61 25 b) [3:It-[1 (1 .,3-17-t [2..(3-"'hlcar'a-4..
m 7hC~+y'~i;.:~i~~)~;,~:iopEU,~yljaininoJ-5-(propyithio)-3HH1,2,3-triazolo[4,5-d]pyrimidin-3-y'i ~cr;ii.ig io the ine 1 vf E;t.w.ipte F, step (b) using the prodtz:,t of ;tep (1).
~, M~' ;iUt)cIo).
30 Ni~ ~R' 1SO) 9.31 ;'r~-I, d). 7.P-7.65(3I4, rn), 5.0{' (111. q), ~l.ji;_j.~
I(l 1-77 m), 3.i~f!-?.Kt= ( '::w4 ni) 35(3 (39, )3 'i4-3. T:1 (2I r , ta), 3.1 ! -3.07 (1 f-1, r.a), 3.03-2.:4 (2H, m), 2.31-2.21 (ili, m), 2.07-2.00 ;2H, m), i.SO-i.80 (111', m), 1.58-i.48 (311, m), 1.33-1.24 (1I-!., rai,':~.;t4 35 ExnRn.piP 97 WO 99/051.43 PCT/SE98/01393 [1R-[1 a.(1S*,2R*),2 (3,3 (3,4a)]-N-[3=-[[2-[3-[2,3-Dihydroxy-4-(hydrox.ymethyt)cyclopentyl;-5-(propylthio)- f=H-1,2,3-triazolo[4y5-utJpyrimidin-7-yl[amint;;cyr:.toprrepyllphenyZj-rrxethanesuiphur.tamide s a) J3aS- [:3ark,4o,,r *,2S'1),6a,6aa]-N==[3-[2-[3-[Tetrahydro-6-(hydroxymetbvl)-1,=,2-dinxeL',iyi-~~H.-c;r r.iopenta-Il,3-dioxol-4-yl]-5==(nropylthio)-3H-1,2,3-triazolo14,5-d]pyrimidiii-7-ylamino] cyclopropyl] ph enyl] -methanesulphonamide The subzitie coinpound was prepared according to the method ofEx;x:n,pie 1, s,ep (a) using the pronucr of example ~4, step (d).
MS (APCa) J90 (M+ff(Ju'Io).

b) [1R-[la(1S*,2R*),2[3,3[i,4a]]-N-[3-[[2-[3-[2,3-Dihydroxy-4-(1+.i-~l. ")~zs=~"=iethyl)cycioperptyi]-a-(propylxnit))-3h=1,2,3-triazoio[4,5-c+?pyrirai,uirY-1-yl]amtno]cyclopropyl)ptaenyl j-methanesulp .-onamide TiLe sumiti-, conipound was prLparaJ according to the methua oi Example 1, step (b) using the proctucr of s*~ra MS (APCi i i'C1 (Ni+Ei'.1 0017o'~
NMR SH tiJ<-I?NiStJI) 9.62(il-t, s), 9.32 (1H, d). 7.25 (1H, t), 7.05-6.91 (3H, m), 5.01-4.95 (2H, m), 4,74I-4.70 (2H, m), 4.43-4.40 (1H, m), 3.87 (1H, q), 3.49-3.43 (2H, m), 3.22-3.19 (11I, in), 2.98 ('i:-I, s),. 2.4:3-2.86 (2.H, m), 2 l7-2.:"'_3 (IH, m), 2.13-2..08 e2H, m), 1.90-1.80 (li-{, m), }.5"~-{l~' (it-Y, rn;,'.2!=>-,'.25 ,a'f-f, rni~. 0.83 i3M; t).

ET.Anxple 11~8 [13-[]tV Il;>,.(3,5-1'"irnet}~~a~ypbenyl)cyclc~propyl};~mino)-5-2s E,2,3w.:~i:.:s1~'~a,5-st;~r~rimarlir~-3-y1}-5-(hy'dr xgrr~et.hyl}-c~e:Upentane-tC trl0 111E.;~i4~ t)I E}:~t17I'La.10 1, :ii:~JJ ~iu=: ail.Ilg tta")rr.C.li"..1; 1:Cf::~I.7plP.' 64, St.'p '' 3), ~c).'~~~~'~~; tl~' :fa= :Tlle'Yii 1 O: (b;.
;1 ~t l? i M3(.~:. 0 Nialk 0; ).3? (111. 16.35-6.3G (3ii, 4.93-?.95 (21i, 4., =+.7fl (2H, m;, (.11, m), 3."i3 t6H, m), 3.49-3.47 (2R, m), 3.22-3.18 (1H, ni;, :U (iH, :! .:iU-2.US (21.-1, m!, 1.92-1.81. ( t! ~, rri), 1.60-1.40 (2.,1T, rzi), 1.0 - 1 .2 0 m), 0.84 (3H, t).
*rB

[1S-f 1a,2rjs3J3,4a(1S*,2R*)]]-4-=[7-[[2-(3-Fluorophenyl)cyclopropyl]aminoj-5-(propyPthio)-3 i=i'- 1,2,3-tri?~zolo [4,5-dlptirrimidin-3-y1]-cvclopentane-.i,2,3-triol a) [3aS-[1(i,),-":4a-,6a,7ap]j-1-l,3-(3=.=Fluorophenyl)-1-oxo-2-propenyY]=-hexahydro-8,8-s dimethyl-3H-3a,6-methano-2,1-benzisothiazole-2,2-dioxide The subtitl: compound was prPpared accordi7g to the method of exarnple 19, step (f) using 3-(3-fiuorophen.yl)-2-propenoi.c acid.
MS (APCI) (M+H+), 364 (100%) io b) ~3a ~..o~n.1;~ ~i ~s;~,~y:)~sact,~,~t,ta~j1='.~-~["2w(3-z luc~rcp~lter~~l)cyclopro ~ h~~nyl]-hexa.h) drci-i3,~3..dimethy,l-311-3a,6-yxie,th:ano-s ,1-befnzisothiazole-2,2-~.ioxido:
The subtitle compound was prepared according to the method of example iy, step (g) using the p:-r:ducr. of step (a).
~Nl+tl',1vU'%) NiS 4Ai'(:is 378 c; ~ 1.1t-trw ~-,~s=a-:4-(3-F+'faorc,phenvl)-cyclapro!panecarboxylic .tcid The sui-titl cor-rrunc! was pr,~nared according to the method of exarnple 19.
step (h) using tl-ie pructuct: oi' s; trp (b).
Nivitt~,H ;.36-1.4'=3 1.65-i..i1 (11H, rn), i.S6-i.~4 56-2.63 (1'H, rrt), 5.71. (l't!. d.,,)=9 9 147), 6.,88-6.9a (2Ff,,,.n), "?.21=7.29 (1H, m).

d) (1.7?-if?,o~v-.)-2-(3-Flnioronhenyl)cyclopropanamine, [R-(R *,R*)j-2,3-d-"hydrex-yb=.-tanedioate (1:1.) Tne subtiz.:c: ::Dri,pour.d was repared according to tize zna:iod o ex,~r.t~he 2C, step (b) using the pr: cu ;- ';f s.:? C.
NMR 6H. (df-r!tV.tiO) 1.12 1õ29 (2H. ni?, 2 12-2 18 (1H, m), 2.69-2 74 (1 H, r;i), 3.95 (2H, s), -.2"1-7.34!, llli r,:,;

e) [1S= j ? a,:Mf 5*,~ ~'';;j-4-[ ;-t12.-(347l;uorophenyl)cycloprlj~ aminU]
..5-(p.-uipyltlddz,)-314=-1,2,:i-tripzolo[,;~,5-djpyrixniclin-3-,ylj-cyclopentane-Y,2,3-triol Pif, t- l; c.vii;,ourd i4va3 nc~.,?a.-ed according +.o the method of exarnple 24, step (f) using the producrs of step ,nli and exainple -1,4, step (ci).
Mi, t.~a t:y<<<'s 1 '/t:.i , 1:)C%) .._., (lij, m), 5.10-m), 3.7 9 (IEI, s;, 3,2.5-3.19 (113, m), 2.99-WO 99h1514:i PCT/SE98/01393 10., 2.73 .'2H, m.), 2.65=-2.55 (1H, m), 2.18-2.11 (1H, 1.96-1.87 (IH, ri), 1.61-1.35 (4H, m), 0.81 (3F, t, 1=7.2 Hz).

Example 100 s [1~i"-[I tvdl;~ X-?~t,~),2(3,3~3,4a~.~]-I~ [[3-[2-[3-(2,3-Dihydroxy-4-hydroxy metliylcycinpentyl;-~~'-(prop',,lthio) -3.?5f-1 y2,3-triazolo [4,5-dipyrimidin-7-yl]anninc,] wyi:#opropy!] phen.yl]-acetamide Prepared accordi:.g tc tnt; tnf;t.had o: :t/xample i, step (a) using thF;
products of example 87, to step (b), foilowea by the method of Example 1, step (b).
MS (APCI) 528 (TA+I'=I', 100%}.
NN1R Slri (cdh-DMSO) 9.86 (1H, s), 9.32 (1H, d), 7.41-7.36 (2H, m), 7.22-7.16 (1H, m), 6.6:'-6.c.3 (llt, m), 5.61-4.95 (':;J.~i, in), 4.) 1-4.45 (21i, m), 4.43-4.39 ('H, in), 198-3.85 (II-i., m), .S.J1-3.45 (211, m), 3.11-3.i8 (lri, in), 2.9"7-2.83 (21'-i, r,i), 2.2; -2.05 (3li, m), 2.05 15 (3Y-i, t), 1.89-1.'i9 (1ft, ln), 1.55-1.50 ('sH, m), 1.48-1.26 (1H, m), 0.83 (3H, t).
Examr~le XiJ~
[Ih-[10c,Za,3(3(f R*,2.:'x),u13?;-;s-[7-1t2-(3,5-I)ichlorophenyl)cyclopropyl]am;.n.o]-5-(propyitnir)- 3.iF1-r,2,3-triazoi o[4,5-d] pyriniidin-3-yl]-5-(hyd roxymet hyl)-cyclopentane-20 1,2 diõ1 a);3 a R-['--,,i or..4 rx~tiai yi k,:tS*'),#,aa]-6-f7-[(2-(3,5-Dicnloropihenyi)cyclopropyl)amino]-5-(propylthio)-3H-1,2,:;-triazoi o[4,5-d] pyrimidin-3-yl]-tetrahyc:4ro-2,2-dime!
hyI-4H-cy-;:loxaer~t,;.~-:+~;3-~:
25 Prvparcd a:.cor di:.f; to the method of Example 1, step (a) using the product of example 83, step trt;
M;y ( ,LQl:l) (PN1+l-f, b) tt5-.,ichlorop3erayl)cycl",r~ i= ap3'I]4:1?:ilno]-5-30 (p: ~l-~rlil~wo j:i~.'-1;?."l-h-~a::a';: i4,'.' r!]t~yr-midin-3-yl[-5-(hydroxymu:th'Jl.}-cyclopentane-Prc~;pa.rc:4i u. ,~;;rdi.1- to the inettiod of Example 1, step (b) using the prcduct of step (a).
nr~:.~try t'18 colurrn. 0-1 % aqu ous ammoniuzn ace:r~rrF :ar,e ciz;i: 41: ,: s;;crat?~, r: ~u'ion f'Ct% Me("N over 30 1~inrtes) affor iPd the title 35 co:n,<)-t.nd (98rri~a).

WO 99i0~143 PCT/SE98/01393 NMR 8H ,((lt-DIti:;iC)) 9.39 (1.I-I, d), 7.40 (1H, s), 7.31(2H, d) 7.23 (:ii.
s), 5.04-4.97 (2H, m), ,1+."'4-4.."7'J (2ri, rri), 4.39 (1H, m), 3.89-3.85 (1H, m), 3.51-3.45 (2H, m), 3.19-3.10 (1H, m), 2.93-2.80 (2H., m), 2.30-2.20 (1 H, m), 2.10-2.06 (2H, m), 1.89-1.79 (1H, m), 1.67-1.49 (1H, m), 1.58 (1H, m), 0.84 (3H, t).
Exaanple 30:' Modifications to the 7- position of {1S-(1a,2(x,3(3,5[i)]-3-(2-Hydroxyethyl)-5-[5-(propylthio)-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yl]-cyclopentane-l,2-diol io a) [3aR-(3a(x,4a,tia,6aa)]-fi-[ I-.Amino-5-(propylthio)-31'1=1,2,3-triazolo[4,5-d]pyrimidi:n-34y '=.tetrahyclrct-2,2-drmei:hyl-4D-cyc3open a-1,,3-dic:t(t le-4-ca.rboxylic acid A su~~ut,.un of the product of example 6, step (b) (1.40g) and ammonia in 1,4-c:ioxa:le bJ ~rj) was stirred at 50'C for 3 hours. 7:'he reaction mixture was evaporated to is dryness, the reslclue tritui-ated with water and the subtitiE cotnpounci isolated by filtration (1 ~, MS (F, RC:t;; 395 '?'v1+1-[+, 100~/~) b) I3a R-(3a a,4rx.laa,baa;' -bv j ; -Amino-6-(propyithao'-3tr'-1,2,3-triaa,oiol4,y 20 dpyrimidin.-3-yl]-tetrah,ydro-2,2-dimethyl-4.H=cyclopenta-1,3-dioxole-4-a wetic acid, metinvt ester Isobutvichtoroforrr.ate (0.33 mJ) was addeca to an ice-cooled solntion of tne pror_uct of step a) (0.50g) a.r.a ~'-zne hylmorpr.op.ine (0.26 mi) in terrahydrofuran (10 ni').
The soiution was stirre-,i at aocyri7 temperature for 60 rriiriutes ther, added to a soiuaoii of tliazoiiietllane 25 (l.!~ _ ~ : tr~~r (1t~1~r.'~ 1'r.A f;,li~xi~~n wG., stirred far t~0 mintites ~he_r: :,nnr,~*trrated. The cnillo dir7ni:.t;'cT.: ((E.50 ?),vas ,al:e1 iritr+ mntY zol (20,0 and sil~ e, (T) oxiri-. !250 mg) addnd pr~iti,~r.w~..c at 60''C. The Lnixture was heated for 3 hours, diluted with chloroform (1t1a? r~'_~ the i shaken vigorouslv wit_h 0.88 aqt.)eous amr.nonia (50 ml}
anc. zva;~r (.5(1 ml) for 20 -ri~r._ 1 y~, mi.yture was extt-ticted into chloreforro and. the extrarts washed with water 30 tht':'ir (11ied Ct'm:entrate(j, l'l'.rif! Catlr)l~ 1' I as cLtiar::t) 811i')rded the suLCi0? ~U,ll~)ouilQ 19.J\Jg).

7~,~S (Pt..~.C"').i 1 LV;.~,g'd'i', . r. ~
~ =~../ , . .. ~1o~~vi), lV:.

C) I
.P~~
35 [~13'71'er17C~~?~-:~-v!'-tQtra}1Vl~.rO-.',~,-f~r.m~f!}yi.~.i3lcvc.~t-n-enma-_#.,.~-~!

WQ 99015143 PC'i1SL+'98/01393 1C"' DIBAL-'rr (1.5 M solution in toluene, 5 ml) was added to an ice-cooled solut::o:i of the product of :gtep li) (0.20 g) in toluene (10 nil) and the solution stirred at this temperature for 30 rninutes befcore adding water (2 ml). The product was extracted into ether, the solution filtered through a pad of celite, dried and coricentrated (175 mg).
The resultant fon.ri Q 75 -r.gl was taJcer intobrnmoform (5 m1;1 isor;rnyl nitrite ( 7rr l) t-;r '; a-:' at 85 C
for =~~, ~nirutes. Ti~e s~~lution was con~centratec~~ and purified (SiC~z.
etl.aer:isoher,ane 2:1 as eluant) tc afford the subtitle compoutld (0. 15g).
MS (APCI) 400 (M+H'-57, 100%).

d) Modiiricar:;tons to the 7-position of 11S=(I(x,2a,30,50)1-3-(2-Hiyaroxyethyr)-5-15-(propyrthio)-M -1,2,3-triazoloJ4,5-d]pyrimidin-3-ylJ-cycYopentane-1,2-diol The product of step c j(2.5xiu- mol ) in 1,4-dioxane (90 i) and N,N-dil~.opropyiethylamine (1.Jx! J"i.:oi) in i,4-droxane (i00 ~) were addeci to each or the azriirie sair:; iisLcu bciow (5.Ox 10-sniw). 'i'rre reactron mixture4, were heated at O'v"C" rcr =1 110ars i;tsrore ariurng phtllai.a.te bR.irfer (pH4, 4u0 I) and extracting with ethyl acetate (4 x 200 1). The extracts were carc.e.n-trated. and the residues taken into 80% acetic acid (150u.1)-then heated at 80 C
for 30 minutps, The reaction mixttires Pr? conc ntrated then azeotroped witl~
ethanol (2 x 200111) to aYfnrd rhe titie rc;npounds.

The iollnwirau amines wer ~Ysed (Preparations dPscrined previously ir the ex erimental):
(1,5-~ran,s)-N-3-[('s'-.Aminccyclonropyl)phenytj-methanesulfonamide, [1t 1-2,3-dir.yd ~;Xy~aaaTe (1~~, I!'~1YaS)-~-(~-~yileil~3Xyliht,'Ilyi)Cy"C~Opr Gj~iindfYllri:, ~!i (~*,.i~~ ) u dilr~~,a-;rr~ta:n, doat (_:1-(1X, ~r~;-rzsw Z (~. pfr;~.icxy;a:,~~.~iyl)cyclopropanarnin~, dihy=lr.ox..yi.;s:zitiedioarc; (l:

(l ~~
(1R-trans)-2-[(1 i'-biohe,:zyi)-2-y?..Icyclopcopanarnintt di:r ( lli-ira;.:j' )-2-[( i, i..biphcriyi)-3-yl jcycioprc;pariamirte, [!t-(A*,R'-') j-2,3-dih:y(arox.v'biixanedioate (1:'o WO ')l r~S 143' PCTl~.'E98/01393 1t;$
(1R, trans)-2-(3,5-dichlorophenyl)cyclopropanamine, [R-(R*,R*)]-2,3-dihydroxvbutanedioate (1:1) (1 R, trans)-2-(3,4-dic-~lorophenyl)cyciopropanamine, [R-(R*,R*)]-2,3-dihydroxybutanedioate (1.:1) s (t ~'~ ~{õ'r'~ ~ -'3-cl-ilcro-u-roethoxyphenyl)cyclopropanarnine, [R-(h'*,.n'~~i- 2,:? -dihydroxybutar.edioate (1:1) (1R, trans)-2-(3,4-dimethoxyphenyl)cyclopropananiine, [R-(R*,R*)]-?.,J-dihydroxyb-,.tanicioate (1:1) ( l:i'-trans)-A;-4-1,(2-Arunocyciopropyl)phenyl]-acetarnide, [R-(R'~1,kl')]-4!,3-1o ditiydroxy'butanecioate (1: i ) (1R, trans')-2-(3-chloro-4-nletnylphenyl)cyclopropanamine, [R-(R*,R*)1-2,3-dinyotroxybutanedloare ( ): : ) (lh, ,,=c.;a,;)..a-',t-.cr.uorct---,-rnetnyiphenyi)cycloproparamine, dinyuroxybutarieaioate (1: 1) 15 (1R, trans)-1-(4-tluoro-3-metnyiphenyl)cyclopropanamine, [R-(R*,)t*)j--2,3-dihydroxydutanedioate ( t : j;
("ilZ, trans)-),-(;3-nitror)heny:)cyclopropanamine, [R-(lt*,R'k)]-2,3-dihydroxybutanedioate (1:1) (1 R, transi-,; -(4-.-rzetboxy-3-metnylpiiznyl)cyclopropanamine, ")]-2,3-diny~cirox;~h, t~.ne~,oa~P i i: t) (1k, ~raras+-:-("-rr:Pthox.y-l rr+_earlylptienyl)cyclopropanamine, {R-(k*,R*)]-2,3-dihyciroxyb,!.taned.ioate (1:1) (1R, trans) -2 -('-r',IV-dim.etryiphenyl)cycloprup~uiamine, [X.-(R*,R*)]
dil-.ydrox;i~i,,tari dioat(: (d:i j 25 (1,'?, tran:;',-<.-t"-,,4-dij'+aoro,).Iienyl)cyc;opropanamine, [R-(R*,R*)]-1,3--dil~ydroxyb~.t,r,~;edi~sat (! lta >,-a?z,;~-,!.-r; 3, ;-c:il!.~u)rophenyl)cyclopropanarrune, [R-(R*,R*)]-2,3-dl' (-lls', :'r~~rr,y + !-!;,9 cit!c7r,~pite:~ Yi)cyclopropanan 6.;,).e, (R-(1Z*,,R*) j-"L,3-dihydroxyt)utanedioate Wt, traras ,? '-fi cLlc;rc~l he:lyl}cyclupropanurr.ine, tR-(k'*,R*)j-2,3-dihydroxyi7utanedioate (t'1) (1.R., trans)-~,,-~.4-r.:etiioxyp.i;:ny,)cyclopropanamine, [R-(R*,R*)]-2,3-di..ydrox;bc:t.r,necii~ate 3s (tl~. ;ran,>1-:~-,"~--; .eti ox.~p.~enyi)cyclopYopanamine, dt.;.y~clt;_~~

~_~..~.~.........~_----WO 99i05143 PCT/SE98/01393 (1R, trans)=-2-(3-rr-ethoxyphenyl)cyclopropanamine, [R-(R*,R*)]-2,3-dih.ydroxyt,c.~ar:cdkoa;- (1:1) (1k, trans)-2-(3,5-dirn..thylphenyl)cyclopropanarnitle, [R-(R*',R*),-2,3-dihydroxy:X >ar,.ed;oa!:,: (1:1) (1R. t-~-rs)-2-(4-Ã1uorop;aen.yl)cyclopropanamine, [R-(R*,R*)]-2,3-dihydrnx,thii ta.n.edioate (1:1) (lk, trans) -2-(3-fluori)phenyl)cyclopropanamine, [R-(R*,R*)]-2,3-dihydroxybutanedioate (1:1) (lk, trans)-2-(2-metnyipt-renyi)cyctopropanamine, [R-(R*,R*)]-2,3-dihydroxybutanedioate io (1:1) (1k, trans) -Z'-(~-rneth~ tphe .iyl)cyclopropanamine, [tc-(R*,R*)]-2,S-dihydroxybutanedioate (1:1) (lR, tr-arls;-:---(4-m.eth,y:pher~yi)cyclopropanamine, [R-(R*,R*)]-2,3-azryaroxyoutariedioate (1~') The. following procla~4s were obtained:
a) (aR-[l2,".~',3~-,-1aJ] N-[3-[2-[(3-[Z,3-T)ihydroxy-4-(2-hydroxyethyl)-cyF IopentV-l",5 ~prr~p~ I#hin1..31~ 1,2,3-triazoio]~:.5-ciJhyri aidin-7d yl~~~nino~+~vr,l~~p~-ola} Jphen:ylJ-methanesuifonamide MS ( A.PC! ) 564 (:\,1+11+, ; 00%) b) [IS-[lict,':o~3~i,~,~rp.d'4*,:~~*)]]-3-~;2-liydrd~etF~.yl)-5-('~-[[2-(4-phenoxyphenyl)cyclopropyl]aminaj-5-(propyltliio)-3H-1,2,3-=tr-i.-zolo[4.,5-4]p:9ri:~,ai,Y..~..,,~]_,~.rl~a;~~ra#ane-~5~
NE, {1~11c. lr J (14'~f l i, 11 'J u/0) c) iiJ-iic,~;,~,sN,~~t~,~'%,~tt~)]1-3-(z-)riiydroxyethyr)-5-[7-[[2-(3-pts.exna :31~he ~}Ij,r.~r.l~aP~'opYi].a:rninc-] S (;Prop3Zt11io)-l.~1-1,2,?,..tj= a~.cTr~~.',~ .
cqpyrim.idin-3-yl]-cyclopentane-1,2-diol MS (APi,l) d) x~~~>wl]a~rainn]-5-(pro;nvhrh;ol-3.f1=1.,7 ~-tria~nloj4;5 r~ny.rimRdin ?_yl]_ 5-!7-hydroxyethyl)-r=yclnl7a!esi:~. n..~-,,7- ;iic+t IVS, +;A.P;

e) [IR-11 x,2c.,3!.(Iii*,2S' ),Sp]]-3-17-[I2-[(1,1y-Biphenyl)-2-y1]cyclupropyl]amino]-5- -(propytthio)-3H- 1,2,3-tr-azolo [44,5-cTi pyrftatidin -3-yi]-5-(2-hyd roxyethyl)-c,yclc pcil:aae-1,'-e;iol MS (APCl) 547 (A+Ir', ].1)~t'~'!o) f) I3R-[Ia,2cx,3~(liry*,2S*),5(3]]-3-[7-[[2-I(l,j'-Biphenyl)-3-y1]cyclopropyl]amino]-5-(propyy thio)-3R=1,2,3-triazolo(4,5-ti]pyrimidin-3-yl]- 5-(2-hyalraxyethyl)-cy4.lapNis~!:at~.-'_, MS (AK-I) -,)4 /' (:), i+lOCW, g) [i,k.=iaa..2cc,:sp(tR*,2.s"l,),5p]]-3-[7-[[2-(3,5-Iyichlorophenyl)cyclopropyl]amino]-5-(propyitiiio)-3H=.i,2,:;-tr~azolo [4,5-d] pyriniidun-3-yl]-5-(2-hyulro:zyethy;)-cycr'opentane-l,2-diol MS (APCI) 54i, 543 (M+H', i0O Io) h) (Pro~nylthi rl-;3~?'-'.,2,?=-te-~ aoes,i4,~~..r!],yyric~.idin-3-yi?-S-(2 h}'droxvethyl)-c.y.clopentane-1,2-diol NiS (Ai~(D) ; ~.. 341, 543 (,k ~---ff" , 100%) i} [1FC-[Yc:r2~.:3~?(11~*,ti.~*'~;:i~;]?.:3-T7-[[?-!3-C.lrlor~-4-metlr oxyph~,r,vljcy,,,I:IZ rc pyI] a.rxiino]-5-(prorylth.io)-3H-1,2,3-tri azo--lo f 4,5-d!nyrimidin-3-yl]- 's-(~-i yd, ru,x; rL, thyll -cy.,lQ,pert taaae-l;1-diol 1 ::i I]am~i.no]-5-(prc~? rltAa:;~ ~ r~!='_ r,: .r ~;,cl~a[4,S-d]nyrennidin-3-=l?-5-(2 hydri)-rN7e+!hyl)-i;i~clopentane-1,2.klto!

k) Pa~~~l*-ox~~e~hyll-cyclo p cr .3 p.'lrl,i,,)_ Jri.t,.?;3-x~=d~~r~1n f4.5-~''pyr:mi.ciln-7_.
yl] art.i no] cyclopr:)pyl] phenyl]-acetamide 111 metL~;il pr<ap,ylthio)-3S-1.,2,:3-~.ius.o1c+[4,5-a'jpyrimidin-3-yl~-Wj-("~ h~ airt~ ~y~rl~.y: p-.c~,z?ol~entane-l,2-diol MS (A1-C::1) 5 2 1, s1 ;iVl100%) m) [LR
methylphe:2 y'!)cyclo,tropy!]amino]-5-(propylthic))-3H-1g2,3-trryazolo[4,5-r1]pyrimidin-3-yl]-5-(2-layf:lt=oxyeth.~l)-cyclo pentane-1,2-clicl MJ A az~i) J L 1, 519 (Ni fli~, 1;,+G"lo) l0 nj i:~,'-~it:,,.!~.. -~ r h,~
metliy.lghi,ra3lia(.yci.opropwt[:=icnino;-5-(prolrylthio)==3H-1,2,3-triazoGo[4,5=-c~,pyrimidin-3- yh-~ ~c-1-.ydroxyethyl)-cyclopentane-1,2-diol MS (r1I'i.;l) j iy (iv1+f-i'-", ... c ;'o) !s oj 1~~*,2.~t*)~I--~-~'i'-fllyd~ox~etlayll-5-[7..[[2..(.3-r nitrno~?~xr~~tl~yt ,~ana~r,vlJ~rrti~o]-5-(pronylt~~o)-:~H-1,2,3-tri~~ 010~4.5-d!~pvrimidin-3-y.1?-~~/'~t~

i-3-(x-Hydrox~~ethyl)-5-[7-[[2-(4-methoxy-3-mexhv!n:~env.'lcvc~r-n-=opw'lamino'-5-(propvithio)-3H-1.,2,3-triazo!o r4,5-d?pyrimidin-3-yl~-cyclope~t;-ne-l. ?.-~iol ~;G;:i=3 s' IaCFI(i);~ ethy11-5-[7-[[2-(3-methoxy-4-. . =
met?k-,~r~~~~n~~ l3r)=411T:,xn;on~.-5_~~xo}nv~thio;+-~Fd-a,?,3-triazofta!a~5_~p~,ri~nsidin-3-y1j-~yclontntane-1,2-diol ,r t ~'RI'', '~ ; /1.i t~ ~ ~ .~ ~~k r'; x, !g ,~," ;,'~I?'~ N-1)imethylpher.vl)cyclopropyl]amino]-5-irtrn,.ivttti:t;i..3t;!-T .2,3-trta~n [4,5-dlPyrirlidin.?.=vl]-5 =(2-hvclroxyet6:y0-c~rcl+~}aentane-a.,7-~i~l / .-. . ,.

s) [l..iZ [1~x,2'rx,3r3(1R*,2.i*t,5;3JJ-3 [7=[[2-(3,4.-I)ifluorophenyl)cyciopropyi]aminoJ-5-(hi opylt~~~; rax;y .thy 0.. cyclopentane-1,2-dioi MS (A.P:1I) 507 (M=-H+, It'~~~) t) [1F-l1c,.y2,a.~.~~1R*,'S*?,S;-J]-3-[7-[[2-(3,5-17iflu.orophenyl)cyclopropylJaminoJ-S-(propylthio)-:+H.-1.,.7,,3-triazp)io[4,5-dJpyrimiclin-3-yl]-5-(2-hydro-yy,?thyl)-cyclopentane-1,2-diol M:i (A1-'C:,2 5 J7 (iv1+I'1 , 10t1';o)' to a) [1.R-jla,Z a,3(3(1f! *,2,fd'*),5p ]J-3-[7-[[2-(3-ChEorophenyl)cyclopropyi]a:nino]-5-(pr,)pylt:hid,)-3I~"-I,.'~',3.-~rrisazaEN)[4,y-dJpyrimid,,'in-3-y1]-5-(2-hydroxyethyl)-c.yclopentane-1'A" =, J~ol 50/. .yO.~ ;Ni-+-li' :UO Io) v) a,~:-,!t' ,:! !x,3(',5(3; 1 -3,-(2.Hydroy.ycthyl)-5-[7-1[2-(4-nr~~~tit f~ y ji?s~ryl)cyci.~pr zffrv; y,~s*?i~o?-5-(~earolr~rlth.io)-3_H'-?.,?,,3-triaznlo[4,5-dJpyrimidin-:i-yla ycVclOperntane-:I,2-diol ~IVi~~ ;7~J'; , S~J; (hl +1 ,,, 103%) wj~2 ~+'-i'roc,?~c,~~i,.'~{!1.S*.,2A*)]J-3-!?-livdre-x~~ethyl)-5-(7-[[2-f2-methor.y,nhemyl}cy~lopropWllatrtino?-5-(prapylthio)-3H-1.,2,3-triazolo[4,5-djp,yrimidin-3-ylJ-cyclopentane-1,2-diol I 3 ;~~ jc:;
xl;1~ a.a~c.c,~r.3~~Skyl?'1.~'*,:~~C*)J1.,3.,~2-Hy~lroxyethyl)-5-[7-[[2-(4-.ca~:r+~c.r.i n I:~.Irrr~vR~attaizo]-5-(prone7tthio)-3FI-1,:?,3.triazc~lo[4,5-dJpyrimidin-~- clopentane-1,2-diol . .. , l-?t-!2-la[ydrnxypthyl)-S-(?-[[.'.-(3-rr~~ tjd~m~~noJ-S-(}~ronyttliiol-3,?~?=3,?',3-#ria~olot4,~~-~'!~pyrimidin-3-yl -rv~l n*eenfane- l,.'.-diol *rB

WO 99i051.41?, PCT/SE98/01393 z') iR *,2.ti, r)w5;) -1]-3=[7-[[2-(3,5-Dimethy)pbenyl)cyclop ropyl]amino]-5-(propyltlb.1o)-3t1-1,2.,:t-triazo~o [4,5-d] pyrinr-idin-3-yl]-S-(2-hydroxyethyl)-cyclopentane-I i,-QJ'i ;lA'r I
h1'~3 (A.):,~-. , ,:s'}9 ("~-i-1!~F, yi";1(70;
aaj [11'Z-,1u.,2oc,3[;(''.R*v2..~'*)y55]]-3-[7-[[2-(4=-:,luorophenyl)cyclopropyl]amino]-5-(propyiticic,)-3h=i,Z;3-triazoYo [4,S-d] pyrimidin-3-y1]-5-(2-hyd roxyethyl)-cyclopentane-l,y,-c';c,1 õ ,,..
tVLl:,.
bdt ) [i.r' - [ra,2 c~.,33(1.R*,2S*),'P ]]-3-[7-[[2-(3-l+luorophenyl)cycloprOpyl]amino]-5-(pd opyiti.aw)-3hi=Y,2,~,=trYazcoko~4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl )-cyclopentane-1,I-dioi ivi:i ;Ai'C::Ij 489 1UC'o) 2~''~i]-3=~2-'LLiycl,rx~ etkav~l-5-[~..i(2-(2_ tneskyl~ =~sy:y. /e~icj~ron;~Y;~er~tiFlc:]-5-!;na : p 4,'ihie)-"~I 1,:,,3-~:r,axcl ,j~4,r' ,ijovrimidin-3-y1'-c-,ar.! opentaile-1,2-diol ~i~J., ~.~t.Y.~~ ~ I a:~ ~~ ~ ~V'''d-.'~-(.+ = :.~~J~=I ~
. ~.. . \ f . . . ~ .
rir:)l ~:'-F1n.,2~,3E?.5~i(1S*,? R*111-3-(2-Hydrox3 m:ctk~yl~~h~a~,y1): ~~:I~prr~r~ylranunc~]-S-fnro~-w!thic~)-3~5T-1,2,3-triaz~lo[4,S..t1[oyrimidin-3-'4111 -cvc)ol entane-1,2-dir-1 'ln,i~,:~~?,~~~{?.Sx,2R*1]].,3_{2.,Hy:3rcx:reth~l)-5-[7-[[2-(4-Vr. 'tr 16=11=1+ rn;ti;Cy ;:: nrap~l.thir)-3H 1,N,3-1:riaz+~lof4oS yrimidin-3-;4l7==ryF 'opentane-l,Z-diol .~.~ , t. J
t~.=:.n~<:%-i,'~k:~!l,'~'~..:~'.n*~]]-3-r2_u~ydr~x~eth~~1)-5-['~-(cyciapropylamino)-5-lYt''' s"-'j~,t ~,~ _ ~,/x , ;.t~i,~; ~. ~~. ~_c~l~,yrirnicli~ 3-y'1? dR,l MS A"'C'1) 46' thl-; H.'', 100%) Exaneple 103 [1S-[' a,2a,3(3,5P (1S*,2,R*)]J-3-(2-Hydroxy-2-methylpropoxymethyl)-5-[7-[(2-phenylcyclopropyY)amino]-5-(propylthio)-3H-1,2,3-triazolo [4,5-d] pyrimidin-3-yl]-cyclopentane-1,2-diol a) !3adt-[3aa,4a46a(1R*,2S*),6aaJJ-2-[6-[7-[ (2-Phenylcyclopropyl)amin.n'-5-(propylthio)-3H=1.,2,3-triazolo [4,5-d] pyr=irnid;.n-3-ylJ-tetrahy dro-2,2-diiYdethyl-=4H-cyd:lopen.ta-1,3-=dicixole-4-methoxy]acetic acid, ethyl ester A solution of ':3a:Z-.[3sa,4a,6x(IS*,2R*),6aa}]-6-[7-chloro-5-(propylthio)-3H-1,2,3-triazoio j4,5-a jpy rimidin-3-yl}-tetr ahydro-l,2-aimethyl-4H-cyciopenta- i,3-dioxoie-4-1o methanoi (u.'ig) and rhodium acetat:, (0.39g) in dichloromethaiie (201111) was treated with a soiutiori oi ethyl diazoacetate (0.21 ml) in dichioromethane (10m1) over 3 hours. The reaction mixture was stirred at room temperature for 60 hours, concentrated and purified (0"1j2,1s_,nexane:ethy1 acetate 3:1 as eiuant). ': iie resulting intermediace wus aken into THF (lOml), (1x-trans)-2-phenyl-cycloproparlamine, 1s dihydroxybutanzdaoate (1:1) (0,2g) and.N,N diisopropyiethylamine (0.2m1) was added and the s: loti;~r. srir r,c Fc;. 18 thez r,oncenxra*_ed. l",.iritication 'Sif_i,, ether--'soh.exane 2:1 as elu..arrt) gave the subtitle campound (0.23g).
MS (APC.~~_) 553 ,'M+la;:), 545 (100%).

20 bl !iS-[Ia.:1ee,3[3,5i_i (L+,S'w,2R*)1J-3-(2-1-lydroxy-7-rYtethylpronoxynaethyi)-5-[7-[(2-pheixylevclopr"o4,)-'1)?rm.itzij 5-(propy] r. hin, i-:31f-1,:G<3-tri.azoiol4 .5-rlrztvrimidin-3-y1J-cycloner tan c-1,2-tliol 1'r.j;a.T~ j a:CCCQ.11t, to tn~ m-''IhS)d Jt t x-rll~t-. 'U, using the ;JICGo::t stt'.p (a). Pu.lTlcation 25 (1r~i ,.., 1(;11v C13 S' l.lumi', 0 'I17v Sz;]k;ous arr.monim) acetatC'.<Lce~.onltrl,(. isocratic e' uticii 30 ;" ,j,:CN ~-er 30 *ninute.s) afforded the title compound (115m.g).
NMI2. &H (dE-DMSO) 9.32 (1H, d), 7.31-7.15 (5H, m), 5.00-4.98 (2H, m) 4.78 (1H, d), 4.4 E--1.44 1;r;~_;), a 2) (].11, s), 3.89-3 ts(i t ii=-1., m,), :3.:iA-:3.4t;
'i. ~7 (3H, m), 2.9""~..3~ ": ti, rA1); ; I it?', r.~ i -~. t i A, ..;.~, 2.1 ( lfl, ,.58-1.86 (1H, 30 Plll, 1 43 i."s?-- 1.3 "L (11-1, rr.j, 1.09 (6Ii, s), 0-3 1 (3H, t).
Ex %m.ple 104 [! LL-[? :2"t,-t; >';ll{' J-3-[7.[[2-(3-Ohloro-4-methylphenyl)cyclopr'opylJamino]-5-(propylthio)-3H-1,2,3-triazolo [4,5-dJ pyrimidin-3-y1 l-5-(hydraxyinettiyl j-3s cyelcgientgne-1z2-d!,3l WC c; TS t~c.?. ?CT'/Si?98/01393 11.5 a) 3-(3-(;h)oro=-4-methylphenyl)-2-properAOic acid.
The sub itle compound was prepared according to the method of Example 64, step (a) using (3-chloro-4-rnezhyl)benzaldehyde (prepared according to the method of S.O.
Nwaukwa etal.a 7etral-aedt=on 1982,23, 31 3 1).
N'<< ' . )('.T? 1141 (11i44'11+,' (la%) b) [3aS [1(E'),3aa,ba,7aR]]-1-[3-(3-Chloro-4-methylpttenyl)-1-oxo-2-propenyl]-hexal.d udre;-,8,8-6imeth;yl-3H-3a,6-~nethano--',1-ben:~isothiazole-2,2-dioxide Th;, snl;tinv: r.om~iounc:: wa< -,renarec, ac,.;ord nv .:.o tne method of .
xarxmlc; 19, sf::p (f) using the 1 raiucL ot stt:;p (a;.
MS 394/:392 (ii~'i-H')3y2 (1U0a1o) c) ~;: ~-~1 ~1,'~ k<< ~'*),3 s.tx,tia,'Ia~3]] i-[[2-(3-C~iloro-4-methylpfrrenyl) -8,8-dirrreti~yl-3H-3a,~5=-anethano-2,1-benzisotliiAzole-:',2-dioxicle Th~-, s!iod- rnrr.pourtd -va~, nreliarpd accor:itn; to t.~e methoa of i:;:ampie 1 step (g) usin,g tnp nroduc, ot sr, p 't)) d) (1.' ra'a:Ys;-=2-(3-C:hloro-4-methylphenyl)cyclopropanecarboxylic acid The surt:t.e was prrpai=ect according to the nietnod ot Lxample 19, 3tep (h) uslr,.t; C":e 1)..*f):il.ct d'i? St(:'J ~'.).
MS 1,09 { ~ ~' (, , 7 L (~ %D ) .

e) L;..~C..,:~~ra.<:~,-Z ~;~-~t ~~l,~i~~-i-methylphenyfycyclopropar~amine, [R..(R *,R *)]-2,3-di:~n3dr~

T!;:: ;+ ,C'I i; C:'rr.C' ~::~ ~L'as t;I~n3T,~~ accor iicfl' to the r?ethod cf 1~.xa~n rie "C; sten (b) US1!1,~7 ~.nf': ~'.rnllia~'. ()!.'r;=~ 1~ 1 MS ~.w/ivta.', f) hl~ru-4-ms th'y::. l:es= l)cy clopropyl]amino] -5-(propyithio)-3H-1,2,3-triazolo[4,5-d1 pyrimidin-3-yl j-tetrahyd ro-l,2-dimeth, 44H-eyclopenta-1,3-dioxole-4-m ethanol The co;nT3ound was prepared according to the method cf Pxample 1, step a), using MS (APCI) 547, 545 (M+H+), 545 (100%).

g) [21~-(:~cx,2a,3(3(11~G*,2.:i~),-'~1]-.3-(7-([2-(3-~Ivloro-4-methyl.phemvl) cyclop rQnayl j2imin o]-5=-(propylthio)-3H-1,2,3-triazolo [4,'>-rI]pyrimidin-3-yl]-5= "h d rexymtethyl)-cyclolr.taytane-1,2-diol The title compound was prepared according to the method of example 57, step b), using the product of s:ep +l'f).
MS (APCI) 507, 505 (Ivf+H+), 505 (100%).
NMR 6H (4-L7MSO) 9.32 (lii, d), 7.29-7.21 (2H, m), 7.08-7.01 (1H, m), 5.04-4.95 (2H, m), 4.744.7 t(21f, rri), r=.46-4.39 (1H, m), 3.90-3.86 (1H, m), 3.55-3.43 (2H, m),. 3.17-3.09 (1H, m). 3.iC-2.80 ,2h, in), .4.7y i311. sj, 2.26-=2.20 ( tlti, m), 2.12-2.05 (2H, m), 1 89-1.79 (IH, in), i-5;-i.45 i~.84 (atI, t).

Exampie i6s [1R--i:ioctlS''',z..1?*'),2(3,35y4a]]-=4,-[2-['{3-(2,3.,4-Ti ihy3roxycyclopentyl)-5-(prapylthio)-3H-+.,2 ~=-:r=ia c~ic~~~4 5-~ Ipyrimiiiin-'I-ylJamino]cyclopropyl]phenylsulfonamide a) (?l.1-trern )-4 t2-=~,r~i>ic~yclopropyl'~pihenv9st~Ifonamide, hydrochloride The ..;orn r+oune'. wat ?re,).u'ed frortl( lti-r~ ~ns pi7 ;nylcS
c~.opropana*rii~ie according to the mPCt+o,'. ('I :scai hc~r.t ?-Y ()S 3.497,154.
m.p. 21 1--2 C' NNia.e, &-r +,dE==DMSO) 8.71 (3H, s), 7.72 (2H, d), 7.35 (2H, d), 7.33 (2H, s), 2.94-2.82 (1H, m), ':.4' ? -2.4"_ (; I?, rn), m), 1.28 (1 H, q).

b) [3a~c 6a.a]]-4-[2-[[3-(2,,2-Dimethyl-Fi-hydrox,y-tetrahydro-4H-CyCjfiAX1E'',It~4 "A.J-1~l4i L ~ I, 3=yl) =r'~ ! i)!'b~ yft~If~~l~-:ix t_.~
,l'.t =f:ritd7.0~(-~~.,~-CI~'J"~'.,"l~ilC~ln '~-yl]atl!1 t~~v/' ;!.rll r~t'i l~lrk"l'/:.:L ' O x'1:T'.J ~S:

Prep',.r--i to the, method of Exarnple '-Ar, step (f) using the product of step (a) and theF':~~.~y{ s'.eaidl.
MS +"faPC'. i i1o%) c) (Yk-f 1cc "S -3Ci94x~]-4-;?,-I'(:~-r~.,.t.w-=frzhyrirr..uy-cvc:f? r trf;-ia-=5-.
. , ~
yl]amzfloj,:.vo 4 at" t%n=Vt.u':1c~rc ~n~-de Prepwr i", according to the method of Example 1, step (b) using the product of step (b).

WO 99,'~":5142 ]PCT/CE98/01393 M.P. 200-1"C.

MS (AI=t-Z) 522 (IVI+1T' 1000/) NMR Zt(d,; 1,.40 ( l 1i, d), 7. ; 8(2H. d), 7.52 (2H, d), 5.76 (2H, s), 5.18-4.88 (4H, m), 47 ~ .4.60 (lil:, n), 3.98-3.87 ';1H, mj, '3.81-3.75 (IH, m), 3.29-3.22 (l.H, m), 2.97-2.79 s (2H. ?.65-2.51 (1H, rn), 2.25-2.18 (1H, m), 1.96-1.85 (1H, m), 1.75-1.~-0 0.81 (3H, t).

Exarxipie 106 -.3-=[5-(Butylthit,)-7-1(2-phenyicyclopropyl):amino)-3H-1,2,3-~r.azoio;4t..5-d;pyriniac;irt==:r-y'1]-5-(hydroxymetlayl)-cyclopentane-1,2-dioi a)[1S-[ ta,.Zcx,:~~3,~~(is t,11~ 'w)i1-3-(Hydroxymethyl)-5_j7_~~
phen;yrc ciop copyl)-aminoj-~.-(propvlvulphonyl)-3HY,2,3-triazolo[4,5-'kJpyr.;rrliiiu-3-yl)-cyciop;;n'ane- 1,2-dioi Prepared according to the method of Example 4, step (a) using the product of Example 1, steb MS
b)jlR 3=[5-(.Ruta71Lhio7-[(2-phenylcycnupropvl)arainoJI -3H-1,2,34 ri. .zo'rr-P45;5-dj p7irmidin.--3-yi].=5-(hyctroxymethN:1)-cvclopec.tare-1,2-d'eo1 Prepr!rec: a,:cl+rd',.ng to tne nie.hoa oi :;xaniple 4, step (b) using tne proauct :,f step (a) and butaiiethioi.
MS (,, N<,,;r 4 Y :+ (N1+=Hi*, 1UU16) NMP 4;1: ;c~-; ).N~Snl 9.32 (111, d), 7.33-7.15 15H, m), 5.01-a,96 (2H, m) 4.73-4.69 (2H, m), ir, 5-4.4 3 3.40-3.44 ('?N, rn).. 3.22-3.19 ( lH, ir), 3.00= 2.85 (2H, m), 2.17-2.W (2H, m), 1.90-1.80 (1H, zn), 1.53-1.44 (3H, m), 1.33-1.20 s, ,ij >.
~-, Exarar31e ~ 0"' [1S-[l.cx.2a,,3~~.,.5~i(1-S*,?R*)1,~-3-(Hyiroxyrnethyl)-5-[5-(pentylthio)-7-[(2-phe:; ~;cycpopropyi)amino]-3.4V=1,2,3-triazolo[4,5-dJpyrimidin-3-yli-cyclopentane-l,2-diol Prepi..:e 1 dt; ,vi-dingzj' ('>:1 4, swp C,) using i_ZC; prodLIct of example 107, step !a, zrd Feneare'tu. '.

MS '~la.'' WQU 9=11:5143 PCT/SE98/01393 NMF: i~Vi (dF .T)MSO) 9.33 (":'=;i, d), 7.3; .7.16 (51-T, 'n)., 5.03-4.97 (2.H, m). 4.72-4.70 (2H, m), 4.45-4.40 (iH, m), 3.88-3.86 (1H, m), 3.49-3.45 (2H, m), 3.21-3.19 (1H, m), 3.00-2.94 (114, in), 2.89-2.82 (1 H, in), 2.33-2.22 (1 H, m), 2.14-2.09 (214, m), 1.87-1.79 (1 H, m), 1.53-1.31 (7H, m), 1.2,-1.19 (3H., m), 0.81 (3H, t).
Example 108 [1S-[lcx,2ct,õ 0,5(3(1S~ky2tiP*)]]-3-(Hydroxymethyl)-5-[7-[(2-phenylcyclol-ropyl)aminoj-5-(prop-2-yxy ylthio)-3H-1,2,:3-triazolo [4,5-cf{ pyrimidin-3-yl]-cyclopentane-1,2-diol io a)[1,~'~-{ lcx,bo,3~,5(3(IJ"X;vl~* ~ j 1-3-(Hyziroxymethyl)-S-[5-(mercapto)-7-[(2-pheny cyci(opropy 1):rmino]-3H-1,2,3-triazolo (4,541 pyrimidin-3-yl]-cyclopentane-1,2-diol A soluac;a vi the product of Example 107, step (a) (0.4g) in DMSO (10m1) was treated with sudrum nydrosulphide tiydrate (0.4g) and the mixture was stirred at room temperature for 2 tiaurs. I he nZixture was poured into aqueous bnne (150ini) contain:ng acetic acid (2m.' !,. r ri ex3:ra-c : d'uith etl:.+' acetate ',.~ x 1110m! ). The combined orl;atli~ ext:'acts were dried ani conoenrrated to afford the subritle compound (0.3g).
MS (. AYt;I,~ 41') i000/n) b)[1S-F1a,2a,30,5[3(1S*,2R*)]1-3-(Hydroxymethyl)-5-[7-[(2-phenviewck~-)rop,yljamino].=S-(prdp-2-ynyltlaio)-31Y 1,2,3-triazolo[4,5-djpyrimidin-3-yl]-cgrle:per. A so;.W:xcn o~. pioduct oi :afh (a) (158m.g) ir. :.+!v1F (5m:) was tr:a.eavaitn~V,1V-diise-orc, y": tt.,!ia-ni::e 's8r:.g:t ; o:la ,Jen ny propa;pyt hrom.ide (58mg). 'rh mixture was heated a: f; !' *r,r !?iour a.id ilez pcured intc~ 3queous b:ine (100r~1) ancl extracted 'with ethyl acetat~, L 1COml). The orgaiiic layer was washed with further aqueous bririe (3 x 100m1' ~'zi .,A 1nd concentrated and the residue purified (SiO2, chlorofor.m:mietl:?nol 95:5 as itf:ord rhe title c=ornpound (40mg;.

MS J~Pi-i-F1 ." 1t10cr~1 NMV: riI' 9,44 ; c.), 731-7. ?;a ~ ~iFI, =>Z; , 5.00-4.95 (F:;J, r-' , 4.71.
r;-.7 "j ; 2H, m), 4.44 (1K, q~.. 3.94-31/1 rn), 3.Sa.-')'.44 (2H, rn), 3.23-3.18 (1H, m), 3.05-3.01 (114, cn), Z.2(1-"-+)9 (211, in), (111, in), 1~.52..i.47 t;1:I, m), 1.37-1.36, (i;--i, ra).
Exanqph! 1 tt4 WO 99/05143 PCT/SE9s3/01393 [1S%~ la,2a,,3 5,50(1S*,2R*)]1-3-(Hydroxymeth,yl)-5-[7-[[2-(3,5-dimethylph enyl)cyclo;iropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo [4,5-dJ
pyrimidin-3-yl]-cyclopentane-1,2-diol s a) [:~~tl?.=[?2:~-4.;4o#,6ct(1R*,2:';*),tiaa].3'etrahydro-2,2-dimethyl-6-[7-[[2-(.1,5-dimethylphenyl)cyclopropyljamino]-5-(propylthio)-3H=1,2,3-triazolo[4,5-d] pyrimid in-3-yl]-4H-cyclopenta-1,3-dioxole-4-methanol Prepa..red by the method of Example i, step (a), using the product of Example 94, step (e).
MS ( al/'L!) 52~ k'1Vl+H', 100%).
io b) [1S-[la,2r;,,x0,5P(l.S*..2:t?*))1-3-(Hydroxymethyl)-5-[7-[[2-(3, 5-dimetijyll)henyl)c:ycloprop: 1]amirio]-5-(propylthio)-3d1-1,2s3-triazolo[4y5-dlpy~rrai~~yn-:~-y~j-eyc~op~enrane-l.,L-diol Preparec. by 4he rriethoci oi'i:xainpie Si, step 'u), using the producL or s:ep (a).
15 MS ~"AFCi) 485 (M+H-, 100r6).
NN.i1t (~c~ j~ I~rJia4J) 9.29 ( f.Ii d), 6.85-6.73 (31i r:s), 5.06-4.94 (2H, m), 4.75-4.68 (2H, m). 448-4.~9 (l.h', ln), 3.91-3.85 (1H, m), 3.56-3..41 (2H, m), 3.19-3.11 (1?l. rr.), 3.05-2.82 (2H, ar). 2.32-2.':6 (?H, rn), 2.13-2.00 (2H, m), 1.92-1.78 (1H, m), 11.61-1.41 {3H, m), 1.3'7-i.:' j(s.li, n-). t~.~u-0.8s~ (:Sll, t).
Exa;~frA~e d~Ri [1S-i1a,2a {rj,5[i(lS* k*)ij-3-(;t-Hydrotyethyl)-S-[S-(met:4yrthio)-7-[(z-phexryicyclo;nrop,yl)amino -:3H=1,2,3-triazolo[4,5-dlpyrimidin-3-yl?-cyclopentane-1,2-di6il a) [(2-PhPnylevclopropyl)nminoj-5-{pro 5-d'pyrimidir-3-ylj-te*ral: y 4 r(a-?,2-dirAethyl-4H-cycl . . . , _. .
.
DIE.. , r, !~ ,: ;1. 20%-0 'i,as ad!,:d tu,.n s:,1u* ;,n of t e i ~ , )IUC. i z t prcdo r,: st.c~ -) (.2.W g; in orue:ze (30 a11) a..a the soiutioll stirred at this telr..l;J arur~ tic.icri-, adding etf:yl a.cet.s~ct (2 rnl). The solu:;.on ~,vas w.:shed witta r. ,~tez a, :' :: u:.entrratecl. 'i'ie residue (1.8 g) was taken into ethanol and cooled to 4 C
before addi.-1j: x-r,hlc-operoxybenzoic acid (50-55%, 2.5g) ar,d allowing the reiv-tion to stir at rc;;;,- 14 f10L3:;. :'he solutlo.I n as wasi,.ed with aqueous s.odiuln nleta.;: t' i.t:, U lil' IC,1 ('J :S 16111: j ti;zI. il'1eu. dlld ('~ ri( :
litlalf Gl. ,4'yU 1i1=.::,.1 t:i102, as afiordecl the subtitle compound (1.8g).

MS (A)'ti 1>, 5-.:3 (1Wi+1:1+, 10 Q' %) b)[1S-(icx,2c4,3P,5~ (IS*,21d*)1u3-(2-13ydroxyethyl)-5-[5-(methylthio)-7-[(2-phenylcyclopropyl)amino]-3ht'-1,2,3-triazolo [4,5-djpyrimidin-3-yl)-cyclopentane-1,2-s diol Prepaz=ed by tne method of Example 4, step b). using the product of step a) and commercially available sodiurri methanethiolate then deprotected using the method. of Example 1, step (b). Purification (HPLC, Novapae Clg column, 0.1% aqueous ammo.:iuin a<detate:ac,etonitrile, isocratic elution 30% MeCN over 30 minutes) afforded the title cornnour:.d (I. 10rrig).
NIVii< 3ii (5h, ~m), 5.01-4.99 (1H, m) 4.4u-4.35 (1?I, m), 3.76-3.72 (1H, in), 3.47-3.40 (2h, m), 3.18-3.13 (1Fi, m), 2.31-2.50 (4H, m), 2.16-2.10 (1%1, m), 2.05-~-.Ci, "11i, m), 1.75-1.65 (2H, m), 1.56-1.49 (2H, m),1.35-1.32(1H, m;.

Example 1g1 [1R-[;:.: ;;?-=:'s-(S-()~utyltnio)='I'-[(2-phenyicyclopropyi)aminol-3hl-1,2,3-i1=iazoio[4,5-tt jpyrimidgn-3-yk]-5-(2-nyd.i oacyettayi -cyciopentane-i,l,-diol Prepar d. by 0ti method of E,-ar.-ip le 't, ctep (h) uy?ng the product oi E?xarnpie 110, step a) and butanethiol then deprotected using the method or Example 1, step (b).
Puri*ication (HPLCI+1ow.pak'$ C18 colurnn, 0.1 LIc aqueous ammonium acetate:acetonitrile.
isocratic elution 45 r; Nl-,--C",1 over 30 minutes) afforded rne title compound (210m1*).
NNix bri (d5-T'.~MSO) 933 (i11I.: d', 7.31-7.1.5 (',El, rr.j, 5.01 -4.94 (2H.
na} 4.77 1 H, d), 4.49-4, ~i) (Iti. (Ti) 3.0-.S."" i;1x3, m)., :5.50-.5.48 (211, =r.), s. t9-3.10 !lf-l., m), 3.00-2.85 (2H, rm); 2.3 8 -2.29 (X k4, m), 2.18 L.13 (1H, in), 2.05-2.00 (I1-i. ni), 1:
79-1.e4 (2t1, m), 1.51-1 '~,7? ('IV, l,3f-?.,2'. (:.H, ~'.

Exaw.nle 11:3 [I~t- i-a ~:,::~x,:l ~,;llii';15*)r5~ 9~-~ ['~-[ i2-i4-clnliosoplnenyl)cyclop~' oPS'l~ ar? 30 (propyryraidin-3 .:ylS-Cl,'l=hyarLxy )eda oxy a) 2-111,1A-cas) -4-az:;1o-2-cycdopenten-1-yrjoxyj acettc acid, 1,1-dimethylethyl ester (1.~-('J:i i~ ,~1?'s ic- :-cvc(oret~t~:r.- -ol (:1.4a) (rr2:T?at'P,d ~.4 t,je i r:tcled ~k,' D.I'.DearJoff et al., J. Ore,. [589 54, 175(~) in t.etrak.S l:coF~ac .r~ ; 60r.:; wa.s added drov.,vise t: a suspe:.si;:.n c,!= s,~,d:'..=ti hyd.ric:P (1.1,; of a 60% suspf risinn ?n o;1) in tetrahy :irofuran. t:60m1) WO 99/05142e T'C'Y'/SE98/01393 at OoC. On coripletion of the addition the mixture was allowed to warm to ambient temperature the added dropwise to a solution of terr-butyl bromoacetate (10.1 ml) in tetrahydrofuran (60rni) at GOC. 'Water (200m1) was added and the p:coduct extracted into ethyl acetate (200n1I) then driea and concentrated. Purification (Si02, ethyl acetat(--;s,)hPxane.lu:90, .Es cluent;s afforded the subtitle compound i3.6g NMR SH (d6-:.DMSO) 6.21-6.18 (1H, rn), 6.02-5.99 (1H, rr.m), 4.49-4.44 ( i.H, m), 4.33-4.22 (1H, m), 4.03 (2H, s), 2.72-2.64 (1H, m), 1.63-1.55 (1H, m), 1.43 (9H, s).

b) 2-[[[(1.i=cr',r;)-4-{6-C,'hloro-S-nitro-2-(propytthio)-,pyrimidin-4-yljarnino]-2-1o cyclopenten-l-yijox,y)-acetic acid, 1,1-dimethyrethyl ester To a soiution of the product from step (a) (3.5g) in tetrahydrofurau (250mi) water (25m1) was aadcd triphenyl phosphine (4.3g) and the reaction mixtue stirred at ambient temp~.:ia+.aze, or ttiree days. 't"ne solvents was evaporated and traces o:
rk;rY,oveu by evaporation from toluene. A solution of the re;;rulting amine (3.0&) in terrahydrofuran (100m!.) was added dropwise over one hour to a solution of 4,6-dichloro-5-nitro-2-(propy ltl:io)-1;yrirnidine (preoared as described in WO 9703084) (3.7g) .. 'i he rer,3.ction mixt~:re was Fti:re-.i fcr one hcur the solvents d,vanora~ed Gr.d the pr:~ctuct reoissolved in ethyl. acetate (50111ml;o then wasred wit:: water (20)m,l, 'I'.he organics were separated, dried and eva.porateci. ',wtTrification (SiO~, chyi acetate:isnhey..ane 5:95 as eiuan,*) afforded the subtixie c.ompound z".5 ;), MS ;Az'C:l 445;,114"1 41-5 1l00'%a).

c) 2-[[i(IS-cis)-4-15-amino-6-chloro-2-(propylthio)-pyrimidin-4-yijamino]-2-cycl:pent:ao a(!:14; l,l tõi;~tert~; viei.hyl ester.
Pre~a.rc .d ac.cerd:i~zQ to ti~e mecxlo(i o: exainpiti 12 stz-p b) using the product of s.ep b).
MS (!4t'C::i; 4151e-i i(M-+Nt), 41,i ( l00uo;.

d) 2 '{~ ' ~:i~; =4-17..t;tellla ~-:r=d,~top.)i;~Y~)-3~'t ?.,:~j,;s-traaa,~Zr~i;4,5 ~?l~ua ~m.idsr~.s_vNJ-2_ cyclcar~fiite~-y-~ti"a:ty;-acett~. ac cI ?.,:t-~!i~c~w.t y lethyl E~s~~r.
Prepr:r~d acr..or;diTi- to the rretho-:i or F:x.arr,ole 6, step bl us:.ng, the prc>d.u,,t of step c).
MS (All'Ca) 426/42.8 (M+H), 426 (100%), e) 2-[( _:4 .,rl- rt m icio-5-(lay-opwl*'aicq-:Off 1 1,~;,.4-tr:azolc-[4,5-41 Pyrrm.idin-3-yl]-2-cyclnpeactt.ra-3-yl?ox-yI -:ac:etic: a(ztd, I,;1-dimekb.yletl=11 estcr Prep~ur:r ac cnrclir;; t:) 4he method of example 1, step a; using the product of step d) and i''., ' WO ~,I/ti5143 PCT'iSE98/01393 MS (A.PC1) 407 (.M+H+, 100%).

f) [3aR-'3 ac:,4 f.x,6a,6a(: )] -2-[ [~~'-[7-Ami:n o-5-(pr ol)ylthio)-3H=1,2,?-triaz i71o [4,5-d]pyrina .*,,din-2~-'il]-~~etrahyd,ro-"2,2-dimethyl-4F-cycloperrta-1,3-dioxel-4-yl]oxy]acetic acir?,, F .Y ,d-metllNl ethyl ester.
PrepaLre r according to elie mLthod of exarnple 15, step c) using the product of step e).
MS (APCI) 481 Qv'l+H_', 100%), g)[3a _Y-(:iaa,da,~ a,,6a(x)j-'l-[((w=[7-Brc)mo-5-(ilropyltfino;)-3H-1,2,3-triazolo[4,5-i0 djpyt-imidirs-3-,vl]-tetra.hydro-2,2-dimethyi-4H-cy4lopenta-1,3-dioxol-4-yl]oxy]ethanol.
DIBAa..-h '0.5 r/i soluuun ia Louene, (4 ml) was adaed to an icz-cooied soiution of the product ot step ;) (6.30 g) in toluene (9 mi). 1 he solution sdrrea at N.his temperature for 30 minatie.: bc16i:; atzlc.ing etrlyi acetate (2 :nl) and water (5rnl). -t'he reaction niixtu;e was filtered tri.rou:ah a i!Leselguh.r p;za. wastzed witii brine, dried arid evaporated. Thdt, product is was reciissolved in bromoform (5m1) and isoarnyl nitrite (2m1) ad.ded. The reaction mixture was'~ewtrcWat ST!=' for thirty- Trdnutes, cooled and solvent evaporated.
1'urificatian (SiCh, ethyi acetate:isonexane 3.7 a.~ eluant) to aiforclvd t.ic; subtitle conipouna (t). i ig).
MS t.~.r!: i- 4i,:,' A 74 +l-?), 474 ~1U[tLlo).

20 h)[Ylt-ila.,z r,rõ~B(1R*.':s*).5~j J-3-[7-[[2-(4-chlorophenyl)cyclopropyiiaminoj-5-(prop~ thio)-.:~?~~1.,:f,3.rria~~~ro~~,5-cij?y~~itt~it3zn-.3-yii-5-1{2-t~adroxv)ethoxyj-cyclolr The title compou<ad was prepared accordinn to tr=e =nethoa of example i, step b) using the produ," , cf stc*) ~'.
25 NMR bNl ,.;:i5-1)MSu) 9.:35 t IH, s), 7.33 (1lFt, d), 7.22 (ii:rl, d), 5,15 (2H, m), 4.95 (IH, q), 4.E'_ (111, rj ."~17.3.74 (?.i-i, 3.1 -.dq ('H, Ta;, ;2:", r;:;, 2.ti7-2.'9,'~I-:, t(i),''..:5-2.1i ; f;::I, in;
~0~6-=1.99 (11'i, ;, .. ~ __i3 rn), ..~1-1,44 r'LH. m), 1.:39-?.32 (i13, rn): i).SG (3r'.
+1 +1('Cli :; i <'~
(~,: ..a_) .~.-..,_._, ~2~,-~t~i, ._~1.~ (~.C-i~%,~).
Exan~lrti-:i 1:~
-rjlienyic;ycLiora,l)amino]-5-[(:3,:~,:e-,~-z:s~?~~ ,1.-rczy])t.~iu~ 3tT .".,,:,:~ treaio(u~a~,5-rd~pY~xmiuliii-:~-~1j-cyci;.,i~entane-1,z-diu~
*rB

WO 99A!5:4: PCV.>E98101393 a) [3aR==[3aa,4ay6a(1R*,2S*),t"saa]-Tetrahydro-2,2-dimethyl-6-[7-[(2-phen yi~iy clopropyl)amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo [4,5-d]pyi~imid'im=3-yd]-4hT-cyclo perrta-1,3-dioxole-4E-rnethanol The sabi:rae - Dr~poc.nd M as r)reparPd accorrlin~ to thF; ::ethr,d of Examn?~:t 6, s~~p (b) using s [3aF--f~ -~;,4~ ,6cx.6aa]-6-[[5-a3n;.no-6-Chloro-2-[(3,3>3=
rifluoropr,pyl)tF.:rl-rI
Pyrir.zica:nyl]=-amino}-tetrahyr.ro-2,2-dimethy'':-='~Y cyclopenta-l,3-dioxole-/r-meenanol (prepar=ed as desc:ibed in WO 9703084), followed by the rnethod of Example 1, step (a).

b) [i.5'-,ia,2~x,'~~i,5~-(iS',2~t~)~f-3-(Hydtroxymethy6)-3-1 j-t(z-phEn y. c:yctopropyl)zmi;no]- 5-1(3,3,3-triiluoropropyi)thio]-3H-1,2,3..t:riazolo[4,5-d]PyrimAcatn-:.i-y , -cyclopendar,c;-l,t-i:iioi The tacIe coripr?L.na waa piepared accoraing to zhe metho(i oi Exaxrip;z 1, stc;p (o)t:sing the product of step a).
MS {A)=C:I) 511 (M+H-', 100%) NMR ~--~f (d5-T'sN1SO) 0.43 (1T-1 d), 7 32-7.27 (2H, r.i.), 7.21-7.16 (<H, rn), 5.01-4.95 (2H, m), 4.72-4 70 (2H[. rr), 4.44-4.,J 1(IF?:, m), 3.88-3.84 (1H. m), 3.50-3.44 (2H, rn), 3.25-3.11 (3H, r;~)~ 2.'!-S-2 .70 ("I1-i. rn), 1u (2)!-i, rr-), ).1.S-'?.r15 (?H, m), 1.85-1.78 (1H, m), 1.49- 1.4:i ( t : 1 n~1 b-s..10 (?N, m)..
Exarnfre 1.1.4 [1S-[4. rx,2 (3 j3;: ;,4c<(t ,4*,2R*)] )-J-. [7-, 12-(3-C:hloro-4-xnQthylphenyl)cycloprop7~il] amino]-5-(propvit:niv)-3.f-t-l.,2,3-triazolo [4,5-dj Pyrimidin-3-yl]-cyciopentaaxe-1,2,3-triol of Exr:.mple sf:ep 't;, using tire prcauc.s oi Example 24, s:e "a an=,, rixZvl15:- 't;?- ;!f.Aj (e'~
MS;). 1 NRRP 9.F.5 ,1Z1. 7.:~8 (2Y-, ci), 7..''C'1$?, 701- 1t.'TI, d), 5.02 J). -4.~+~~ :a.li, q;, 4.92 (1H, "'), 4.69-y-.62 (1ti, ,n;, 3.36-3.8y (iri, rn), J'.82-3.75 rn). ].,,~4-2.J'2, (ifl, r7), 2.29 ('sri, s),2:2:i-2.03 (1r4, ni), 1.95-1.86 (4H. rr). '.le"lU (31-1, t).

Phar,ma.cologie:al data The preparation for the assay of the PZt-=receptor agonist/antagonist activity in washed human platelets fo~' the compounds of the invention was caz-ried oiei; as follows.
Human venous blood (100 m:) a,as divided equally between 3 tubes, eacn containing 3.2%
trisodiiuni citrate (4 rnl) as anti-coagulant. The tubes were centrifuged for 15 minutes at 240G to obtain a platelet-rich plasma (PRP) to which 300 ng/rirnl prostacyclin was added to stabilize the -dlatelets during the washing procedure. Red cell free PRP was obtained by io centrifugation for 10 rrrinutes at 125G followed by further centrifugation for 15 ininutes at 640G. I'he supernatant was discarded and the platelet pellet resuspendeu in modified, Calcium Free t yrode solution (lU ml) (LFI'), composition: NaCI 13lmlvi, NaHCO3 11.>nzivt, lval:-'ZPO4 0.4mM, KCI 2.7 mM, Mg02 1.1 mM, dextrose 5.6 m~/i, gassed ,~,vith 95 io 02/5% ('(~2 ~iric rnaintained at s7 (::. Fo'.lowing addition of a rurther 300 ng/mi PGI2, the pooied susperision was centrifuged once more for 15 minutes a~ 640G. The supernatant was cliscarcie~l ~.n.r.i the piatele's resuspended initially in 10 rcLl CF 1' with further CFT' added to adjust the final piatelet count to 2xit3"/". 1'nis final suspension was stored in a 60 ml syringe at 3 C with eir excluderi To aliow recovery from PG~-int:ibition of normal function, plat.eletn were u.sed in ag,gregation studies no sooner than 2 hours after finai resuspension.

In all siiidies, i rr..i aiiruots o-'p~.atelel: suspension were added to tubes containir..~ C:aCI-, solution (60 ~ti of iU mM solution witr=. a ti.nai concentration of imM).
Human fibrinogen (Sigruuy :46:;; ~~..+. i~-sulphr.,,phenyl.:heophyilin.e (i;-S}''i' w#:lcti was used to block any PI-af;onist activity of compounds; were addect to give final concentrations of 0.2 m,g/ml (60 '.1.1 Olf lC' T ~4aTr~ii: i soai~,:)fl CiY Cifitl:$.blE'= pr il1'eEn ":Xi sSlllu:{ and. 301) n1\A (10 itf,l of 15 i?:M
sol'atlnr~ Sll f;iL ~tu+a,1SP.~, reS;)t:CL~t-)~'. i"'1F.itc,ets Oi buffer as ap1]rOj.rY.lte were addeCl in a volt;r v-. '. '-(7 lt,l to th individ.;;:al. wells of a 96 well plate. All mea.surem-,-It:: --.vere made . .. , .
in tr..t ., r<. .., r lar; -l .t, i~rnrn,:.ati;n dcrf.ur.
The ago~aisJ:.:.ta~c;~ist poten;,-~ -:i,as ,as:ze.,sed as fo~.lows.

AggrNg;3t:;:r:.e,-,a,,.nses in 35 =,-, ll plates, were measured us~ng, th:
J,.arige in absorbcnce grveCI by 11-.e, t,'vrE: reacter at 6r;0 ri111. l;irher a Pio- T:c. (_eres 900(' ir a..t)vnatec:h.:\/IP.X
were. '.- : '(1 %. e thr; piute readei .

WO 1'CTSE98/01393 The ;r:' ~~each vs=ell iii, t.: p!at(u was r;.:ad at ~i60 nr.i to e:.tiblisl-i bas(~,"ne figure.
Saline or r:h,t appropr:at.e solution of test compound was added to eac'3 w~-11',n axiolume of },'.1 *"_! Give f~.n,:i', conc(mtration. of 0, 0.01, 0.1, 1, 10 or 100 mM.
Thc: plate was then shakeri for 5 min o:1 an orbital shalcer on setting 10 and the absorban.ce ;read at 660 nm.
5 Agl;r,a7~ ri;)1a i)t t1~'~s,noint tF. as i~rd5.catlve ot' aÃ;CPSi.15t activity of thw test comp(iun(4 Saline or ADP (30 nlll~i; 10 li: of 450 nilVE:) was then addPd to each wel.i and the plate shaken for a furth;,,-:; -ri.i 0, rorf, rC .adir:' ;~bsorhas:re again at 660 nm.

Antzu~::riist ~,ot,:~r.y ~a,as estimatea as a ~?o inhibition of the controi tilit~ response to obtain 10 an ii:50. Compounds exempiiiied have pIC50 values or more than ).u.

*rB

Claims (25)

CLAIMS:

1. A compound of formula (I) wherein:
R1 is a C1-6 alkyl, C2-6 alkenyl, C1-6 alkynyl, C3-8-cycloalkyl or a phenyl group, each group being optionally substituted by one or more substituents selected from halogen, OR8, NR9R10, SR11 or C1-6 alkyl (itself optionally substituted by one or more halogen atoms);
R2 is C1-8 alkyl optionally substituted by one or more substituents selected from halogen, OR8, NR9R10, SR11, C3-8-cycloalkyl, aryl (optionally substituted by one or more alkyl groups and/or halogen atoms), or C1-6-alkyl; or R2 is a C3-8-cycloalkyl group optionally substituted by one or more substituents selected from halogen, OR8, NR9R10, SR11, C1-6-alkyl or phenyl, the latter two groups being optionally substituted by one or more substituents selected from halogen, NO2, C(O)R8, OR8, SR11, NR12R13, a fused 5-or 6-membered saturated ring containing one or two oxygen atoms, phenyl or C1-6-alkyl the latter two groups being optionally substituted by OR8, NR9R10 or one or more halogen atoms;
one of R3 and R4 is hydroxy and the other is hydrogen, hydroxy or NR9R10;
R is a group (CR5R6)m OR7 where m is 0 or 1, R5 and R6 are independently hydrogen, C1-6 alkyl or phenyl the latter two groups being optionally substituted by halogen, and R7 is hydrogen, C1-6 alkyl or (CR5R6)n R14 where R5 and R6 are as defined above, n is 1 to 3 and R14 is COOH, OR15, NR16R17 or CONR16R17;
or R is a C1-4 alkyl or C2-4 alkenyl group, each of which is substituted by one or more groups selected from =S, =O, =NR20 or OR21 and optionally substituted by one or more groups selected from halogen, C1-4 alkyl, phenyl, SR21, NO2 or NR22R23 (where R21, R22 and R23 are independently hydrogen, C1-4alkyl or phenyl; R20 is OR24 or NR25R26, where R24 is hydrogen, C1-4 alkyl or phenyl, and R25 and R26 are independently hydrogen, C1-4 alkyl, aryl, C1-6 acyl, arylsulphonyl or arylcarbonyl);

R8 is hydrogen, C1-6 alkyl optionally substituted by halogen or R8 is phenyl optionally substituted by one or more substituents selected from halogen, NO2, C(O)R6, OR6, SR9, NR10R11;

R9, R10 and R11 are independently hydrogen or C1-6alkyl;
R12 and R13 are independently hydrogen, C1-6 alkyl, acyl, alkyl sulfonyl optionally substituted by halogen, or phenyl sulfonyl optionally substituted by C1-C4 alkyl; and R15, R16 and R17 are independently hydrogen or C1-6 alkyl;
or a pharmaceutically acceptable salt or solvate thereof.

2. A compound of formula (I) having the following stereochemistry:

3. A compound according to claim 1 or 2 in which R1 is C1-4 alkyl or phenyl substituted by trifluoromethyl.

4. A compound according to any one of claims 1 to 3 in which R2 is butyl or cyclopropyl optionally substituted by phenyl, the phenyl group itself being optionally substituted by one or more halogen, C3-8 alkyl, phenoxy or phenyl groups.

5. A compound according to any one of claims 1 to 4 in which R3 and R4 are both hydroxy.

6. A compound according to any one of claims 1 to 5 in which R5 and R6 are both hydrogen.

7. A compound according to any one of claims 2 to 6 in which R is OH, CH2OH, CH2CH2OH, OCH2CH2OH, CH2OCH2C(CH3)2OH and OCH2C(CH3)2OH.

8. A compound according to claims 1 which is:

[1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(Hydroxymethyl)-5-[7-[(2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-(1.alpha.,2.alpha.,3.beta.,5.beta.)]-5-[7-[(Cyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-3-(hydroxymethyl)-cyclopentane-1,2-diol, [1S-(1.alpha.,2.alpha. 3.beta.,5.beta.)]-5-[7-(Butylamino)-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-3-(hydroxymethyl)-cyclopentane-1,2-diol, [1S-(1.alpha.,2.alpha.,3.beta.,5.beta.)]-5-[7-(Butylamino)-5-[[4-(trifluoromethyl)phenyl]thio]-3H-1,2,3-triazolo [4,5-d]pyrimidin-3-yl]-3-(hydroxymethyl)-cyclopentane-1,2-diol, 2-[[[1R-(1.alpha.,2.beta.,3.beta.,4.alpha.)]-4-[7-(Butylamino)-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl])-2,3-dihydroxy-cyclopentyl]methoxy]acetic acid, 1-[[1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-2-Hydroxy-4-[7-[(2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-a]pyrimidin-3-yl]-2,3-dihydroxy-cyclopentyl]-ethanone, 1-[[1S-[1.alpha.,2.beta.,3.beta.,4.alpha.]]-4-[7-(Butylamino)-5-(propylthio)-3H-1,2,3-triazolo,[4,5 d]pyrimidin-3-yl]-2,3-dihydroxy-cyclopentyl]-2-hydroxy-ethanone, 1-[[1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-2,3-Dihydroxy-4-[7-[(2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentyl]-ethanone, 1-[[1S-[1.alpha.,2.beta.,3.beta.,4.alpha.]-4-[7-(Butylamino)-5-(Propylthio)-3H-1,2,3-triazolo(4,5-d]pyrimidin-3-yl]-2,3-dihydroxy-cyclopentyl]-ethanone, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(1-Hydroxy-1-methylethyl)-5-[7-[(2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-(7-[(2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-4-[7-[(2-Phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, 2-[[[1S-[1.alpha.,2.beta.4.alpha.(1S*,2R*)]]-2-Hydro-4-[7-[(2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5d]pyrimidin-3-yl]-cyclopentyl]oxy]acetic acid, 2-[[[1S-(1.alpha.,2.beta.,3.beta.,4.alpha. )]-4-[7-(Butylamino)-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-2,3-dihydroxy-cyclopentyl)oxy]acetic acid, 2-[[[1S-(1.alpha.,2.beta,3.beta,4.alpha.)]-4-[7-(Butylamino)-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-2,3-dihydroxycyclopentyl]oxy]acetamine, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-4-[[5-(Methylthio)-7-[[phenylcyclopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-4-[5-[(Methylethyl)thio]-7-[(2-phenylcyclopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*, 2R*)]]-4-[7-[[2-(4-Fluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*, 2R*)]]-4-[7-[[2-(4-Methoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]cyclopentane-1,2,3-triol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-4-[7-[[2-(4-Methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-4-[7-[[2-(4-Chlorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, 2-[[[1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-2,3-Dihydroxy-4-[7-[(2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentyl]oxy]-acetamide, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-4-[7-[[2-(3-Methoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-4-[7-[[2-(3-Methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S-[1.alpha.,2.beta.,3.beta.4.alpha.(1S*, 2R*)]]-4-[7-[[2-(3-Chlorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*, 2R*)]-4-[7-[[2-(3-Nitrophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S-[(1.alpha.,2.beta.,3.beta.,4.alpha.(1S*, 2R*)]]-4 -[7-[[2-(4-Phenoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*, 2R*)]]-4-[7-[[2-(3-phenoxyphenyl)cyclopropyl]amino]-5-(propylthio)-1H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S-[1a,2b,3b,4a(1S*, 2R*)]-4-[7-[[2-(3-Aminophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S-(1a,2b,3b,5a]]-3-[7-(Butylamino)-5-(propylthio-3H-1,2,3-triazolo[4,5d]pyrimidin-3-yl]-5-(3-hydroxypropoxy)-cyclopentane-1,2-diol, [1S-[1a,2b,3b,5b(1S*,2R*)]-3-(2-Hydroxyethoxy)-5-[7[(2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3,-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1a,2a,3b,5b(1S*,2R*)]]-3-(Hydroxymethyl)-5-[7-[[2-(4-methoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1R-[1a,2a,3a(1s*,2R*),5b)]-5-[[2-(4-Chlorophenyl)cyclopropyl)]amino]-5-(propylthio)-5H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-3-(hydroxymethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3 .beta.(1S*,2R*),5.beta.]]-3-[7-[[2-(3-Chlorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.5.beta.(1S*,2R*)]]-3-(Methoxymethyl)-5-[7-[(2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)~]-3 (Hydroxymethyl)-5-[5-(methylthio)-7-[(2-phenylcyclopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(Hydroxymethyl)-5-[7-[(2-phenylcyclopropyl)amino]-5-[(1-methylethyl)thiol-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*, 2R*)] ]-3-( Hydroxymethyl)-5-[7-[(2-phenylcyclopropyl)amino]-5-(prop-2-enylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(Hydroxymethyl)-5-[5-(4-methylphenylthio)-7-[(2-phenylcyclopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.2.alpha.,3.beta.5.beta.(1S*,2R*)~-3-(Hydroxymethyl)-5-[7-[[2-(4-methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3 -triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane 1, 2-diol, [1S-[1.alpha., 2.alpha., 36,(R*),5.beta.(1S*.2R*)]]-3(1-Hydroxyethyl)-5-7-[(2, phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.(S*)5.beta.~[1S*,2R*)]-3-(1-Hydroxyethyl)-5-[7-[(2-phenylcyclopropyl)amino]-5-(propylthio,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,3S*)5.beta.]]-3-7-[[2-phenylcyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-[(1,1 Biphenyl)-4-yl]cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cylcopentane-1,2-diol, [1R-(1.alpha.,2.alpha.,3.beta.,~.beta.)]-3-[7-(Butylamino)-5-(cylcopentylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]]-5-(hydroxymethyl)-cyclopentane-1,3-diol, [1S-[1.alpha.,2.alpha.3.beta.,5.beta.(1S*,1R*)-3-(Hydroxymethyl)-5-[7-[(2phenylcyclopropyl) amino]-5-[4-(trifluoromethyl)phenylthio]-3H-*1,2~-triazolo[4,5-.alpha.]pyrimidin-3-yl]-cyclopentane-1,2-diol [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*))]-3-Hydroxymethyl)-5-[2-[[2 (4-phenoxylpheny)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3 triazolo[4,5-.alpha.]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1S*,2R*),5p]]-3-{7-([2-(2-Chlorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethoxymethyl)-5-[7-[(2-phenylamino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]
cyclopentane-1,2-diol, [1R-[1.alpha.,2.beta.,3.beta.4.alpha.(1R*,2S*)]]-3-Hydroxy-2-methoxy-4-[7-[(2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentanemethanol, [1R-[1.alpha.,2.beta.,3.beta.4.alpha.(1R8,2S*)]]Hydroxy-3-methoxy-4-[7-((2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentanemethanol, [1S-[1.alpha.,2.alpha.,3.beta.(E),5.beta.(1S*,2R*)]]-3-(3-Hydroxy-prop-1-enyl)-5-[7-[(2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(3-Hydroxypropyl)-5-[7-[(2-phenylcyclopropyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, 1-[[1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-2,3 Dihydroxy-4-[7-[(2-phenylcyclopronyl)amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentyl]-2-methoxyethanone, [1S-(1.alpha.,2.alpha.,3.beta.,5.beta.)]-3-(Hydroxymethyl)-5-[7-[[(trans)-2-(3,4-methylenedioxyphenyl)cyclopropyl]amino]-5(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]cyclopentane-1,2-diol, [1S*[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(Hydroxymethyl)-5-[7-[[2-(3-methoxyphenyl)cyclopropyl]amino]-3-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrymidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(Hydroxymethyl)-5-[7-[[2(4-Hydroxyphenylcyclopropyl]amino]-5-(propylthio)3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, 1S-[1.alpha.,2.alpha.,5.beta.(1S*,2R*)]]-3-(Hydroxymentyl)-5-[7-[[2-(3-methylproxycyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane 1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(Hydroxymethyl)-5-[7-[[2-(3-phenoxyphenycyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.,(1R*,2S*),5.beta.[[-3-[7[[2-3-fluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(3-Fluoro-4-methoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.5.beta.(1S*,2R*)]]-3-(Hydroxymethyl)-5-[7-[[2-(4-methoxy-3-methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1S*,2R*)5.beta.]]-(3,[7-[[2-(3,4-Dichlorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-3-(hydroxymethyI)-cyclopentane-1,2-diol, 1S-[1.alpha.,2.alpha.,3.beta.5.beta. (1S*,2R*)]-3-[(2-Amino)ethoxy]-5-[7-(2-phenylcyclopropyl)amino]-5-propylthio-3H-[1,2,3]-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1R-(1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]-3-[7-[[2-(3,4-Dimethylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl ]-5-(hydroxymethyl)-cyclopentane-1,2-diol, [1S-[1.alpha.,2.beta.,3.beta.4.alpha.(1S*,2R*)]]-4-[7-[[2-(3,4-Dimethylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl-cyclopentane-1,2,3-triol, [1R-(1.alpha.,2.alpha.,3.beta.,5.beta.)]-3-[7-(Cyclopropylamino)-5-[[4-(trifluoromethyl)phenyl]thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol, [1S-[1.alpha.,2.beta.,3.beta.4.alpha.(1S*,2R*)]]-4-[7-[[2-(3,5-Dichlorophenyl)cyclopropyl]amino]-5--(propylthio)-3H-1,2,3-triazolo[4;.5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1R-[1.alpha.(1S*,2R*)2.beta.,3.beta.,4.alpha.]]-N-[[3-[2-[[3-(2,3,4-Trihydroxy-cyclopentyl)-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-7-yl]amino]
cyclopropyI]phenyl]methanesulfonamide, [1S-[1.alpha.,2.beta.,3.beta.4.alpha.(1S*,2R*)]]-4-[7 [[2-(3,4-Dimethoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S[1.alpha.,2.beta.,3.beta.4.alpha-(1S*,2R*)]]-4-[7-[[2-4-Methoxy-3-methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1R-[1.alpha.(1S*,2R*)2.beta.,3.beta.,4.alpha.]]-N-[3-[2-[[3-(2,3,4-Trihydroxy-cyclopentyl)-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-7-yl]amino]cylopropyl]phenyl]-acetamide, [1S-[1.alpha.,2.beta.,3.beta.4.alpha.(1S*,2R*)]]-4-[7[[2-(3,4-Dichlorophenyl)cyclopropyl]amino]-5-(propylthio)1H-1,2,3,-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S[1.alpha.,2.beta.,3.beta.4.alpha.(1S*,1R*)]]-4-[7-[[~-(4-Chloro-3-methylphenylclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol [1S-(1.alpha.,2.beta.,3.beta.,4.alpha.(trans)]]-4-[7-[[2-Phenylmethyl)cyclopropyl]amino]-5-(propylthio)-3H-1,23-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7[[2-(4-Chloro-3-methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-4-[7-[[2-(3-Dimethylaminophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-y1]-cyclopentane-1,2,3-triol [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-4-[7-[[2-(3-Fluoro-4-methoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-4-[7-[[2-(3,5-Dimethylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-4-[7-[[2-(3-Chloro-4-methoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(3-Chloro-4-methoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.(1S*,2R*),2.beta.,3.beta.,4.alpha.]]-N-[3-[[2-[3-[2,3-Dihydroxy-4-(hydroxymethyl)cyclopentyl]-5-(propylthio)-3P-1,2,3-triazolo[4,5-d]pyrimidin-7-yl]amino[cyclopropyl]phenyl]-methanesulfonamide, [1R-[1.alpha.,2.alpha.,3.beta.(1R*.,2S*),5.beta.]]-3-[7-[[2-(3,5-Dimethoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*,2R*)]]-4-[7-[[2-(3-Fluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, [1R-[1.alpha.(1S*,2R*),2.beta.,3.beta.,4.alpha.]]-N-[[3-[2-[3-[2,3-Dihydroxy-4-hydroxymethylcyclopentyl)-5-propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-7-yl]amino]cyclopropyl]phenyl]-acetamide, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(3,5-Dichlorophenyl)cyclopropyl]amino]-5-(propylthio)-3,4-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.(1S*,2R*),2.beta.,3.beta.,4.alpha.]]-N-[3-[2-[[3-[2,3-Dihydroxy-4-(2-hydroxyethyl)-cyclopentyl]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-7-yl]amino]cyclopropyl]phenyl]-methanesulfonamide, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5[7-[[2-(4 phenoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-[7-[[2-(3-phenoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo(4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(4-Bromophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-[(1,1'-Biphenyl)-2-yl]cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-[(1,1'-Biphenyl)-3-yl]cyclopropyl]amino]-5-(propylthio)-3H 1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7[[2-(3,5-Dichlorophenyl)cyclopropyl]amino]-3-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(3,4-Dichlorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(3-Chloro-4-methoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3R-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(3,4-Dimethoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.(1S*,2R*),2.beta.,3.beta.,4.alpha.]]-N-[3-[2-[]3-[2,3-Dihydroxy-4-(2-hydroxyethyl)-cyclopentyl]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-7-yl]amino]cyclopropyl]phenyl]-acetamide, [1R-[1.alpha.,2.alpha.3.beta.(1R*,2S*),5.beta.]]-3-[7[[2-(3-Chloro-4-methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-2-[7-[[2-(4-Chloro-4-methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(4-Fluoro-3-methylphenyl)cyclopropyl]amino]-5-(propylthio)3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-[7-[[2-(3-nitrophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-[7-[[2-(4-methoxy-3-methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H 1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-[7-[[2-(3-methoxy-4-methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(4-N,N-Dimethylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.,(1R*,2S*),5.beta.]]-3-[7-[[2-(3,5-Difluorophenyl)cyclopropyl]amino]-3-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]-3-[7-[[2-(3-Chlorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol.
[1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-[7-[[2-(~
methoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-[7-[[2-(2-methoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-[7-[[2-methoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-,1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-[7-[[2-(3-methoxyphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]cyclopentane-1,2-diol, [1R-1.alpha.,2.alpha.,3.beta.,5.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(3,5-Dimethylphenyl)cyclopropyl]amino]-5-(propylthio)-5R-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.,(1R*,2S*),5.beta.]]-3-[7-[[2-(4-Fluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-,1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(3-Fluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)-cyclopentane-1,2-diol, [1S-[1.alpha.a,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-[7-[C2-(2-methylphenyl)cyclopropyl]amino}5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-[7-[[2-(3-methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-[7-[[2-(4-methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-[7-(cyclopropylamino)-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,1R*)]]-3-(2-Hydroxy-2-methylpropoxymethyl)-5-[7-[(2-phenylcyclopropyl)amino]-5-propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(3-Chloro-4-methylphenyl)cyclopropyl]amino]-5-(propylhio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl)-5-(hydroxymethyl)-cyclopentane-1,2-diol, [1R-[1.alpha.(1S*,2R*),2.beta.,3.beta.,4.alpha.]]-4-[2-[[3-(2,3,4-Trihydroxycyclopentyl)-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-7-yl]amino]cyclopropyl]phenylsulfonamide, [1R-1.alpha.,2.alpha.,3.beta.(1R*,2S*)]-3-[5-{Butylthio)-7-[2-phenylcyclopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2P*)]]-3-(Hydroxymethyl)-5-[5-(pentylthio)-7-[(2-phenylcyclopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, (1S-[11.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(Hydroxymethyl)-5-[7-[(2-phenylcyclopropyl)amino]-5-(prop-2-ynylthio)3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(Hydroxymethyl)-5-[7-[[2-(3,5-dimethylphenyl)cyclopropyl;]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(2-Hydroxyethyl)-5-[5-(methylthio)-7-[(2-phenylcyclopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1P-[1,.alpha.,2.alpha.,3.beta.,5.beta.(1R*,2S*),5.beta.]]-3-[5-(Butylthio]-7-[(2-phenylcyclopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl -cyclopentane-1,2-diol, [1R-[1.alpha.,2.alpha.,3.beta.(1R*,2S*),5.beta.]]-3-[7-[[2-(4-chlorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-[(2-hydroxy)ethoxy]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.alpha.,3.beta.,5.beta.(1S*,2R*)]]-3-(Hydroxymethyl)-5-[7-[(2-phenylcyclopropyl)amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol, [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.(1S*, 2R*)]]-4-[7-[[2-(3-Chloro-4-methylphenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol, or pharmaceutically acceptable salts or solvates thereof.

9. A pharmaceutical composition comprising a compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, in combination with a pharmaceutically acceptable diluent, adjuvant or carrier.

10. A compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, for use in therapy.

11. A compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, for the treatment or prevention of myocardial infarction, thrombotic stroke, transient ischaemic attacks, peripheral vascular disease and angina.

12. A compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, for the manufacture of a medicament for the treatment or prevention of myocardial infarction, thrombotic stroke, transient ischaemic attacks, peripheral vascular disease and angina.

13. A compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, for the treatment or prevention of angina.

14. A compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, for the manufacture of a medicament for the treatment or prevention of angina.

15. Use of a compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, for preparing a medicament for the treatment or prevention of myocardial infarction, thrombotic stroke, transient ischaemic attacks, peripheral vascular disease and angina.

16. Use of a compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, for the treatment or prevention of myocardial infarction, thrombotic stroke, transient ischaemic attacks, peripheral vascular disease and angina.

17. Use of compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, for preparing a medicament for the treatment or prevention of angina.

18. Use of compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, for the treatment of a platelet aggregation disorder.

19. Use of compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, for preparing a medicament for the treatment of a platelet aggregation disorder.

20. A compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, for the treatment of a platelet aggregation disorder.

21. A compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, for preparing a medicament for the treatment of a platelet aggregation disorder.

22. A commercial package comprising a compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, and associated therewith instructions for the use thereof in the treatment or prevention of myocardial infarction, thrombotic stroke, transient ischaemic attacks, peripheral vascular disease and angina.

23. A commercial package comprising a compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, and associated therewith instructions for the use thereof in the treatment or prevention of angina.

24. A commercial package comprising a compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, or a composition according to claim 9, and associated therewith instructions for the use thereof in the treatment of a platelet aggregation disorder.

140a

25. A process for the preparation of a compound of formula (I), as defined in claim 1, which comprises:

(a) reacting a compound of formula (II):

where R, R1, R3 and R4 are as defined in formula (I) or are protected derivatives thereof, and L is a leaving group with a compound of formula (III):

R2NH2 ~(III) where R2 is as defined in formula (I) or is a protected derivative thereof, or (b) reacting a compound of formula (IV):

in which R1 and R2 are as defined in formula (I) or are protected derivatives thereof and P1 and P2 are protecting groups or hydrogen, with a suitable reagent to introduce a substituent R, or, for compounds where m is 0:
(c) hydroxylation of a compound of formula (V):

where R1, R2 and R7 are as defined in formula (I) or are protected derivatives thereof, and optionally thereafter (a), (b) or (c) and in any order:
.cndot. converting one or more functional groups into a further functional groups .cndot. removing any protecting groups .cndot. forming a pharmaceutically acceptable salt or solvate.