SA95160410B1 - SULPHONAMIDES - Google Patents

Abstract

Abstract: The present invention relates to formula compounds, where the variables are as. They are defined here below. Formula I compounds act as endothelin receptor blockers. They may be used to treat disorders that are related to endothelin activities, in particular, disorders of the circulatory system such as hypertension, ischaemia, vasospasms and angina pectoris.

Description

Suiphonamides Full Description General Description of the Invention: This invention relates to new sulphonamides having the formula: Rt RS I 01 N “Mall ed N = R3 RE R7 where that: R! is a heterocyclic ring ¢hetrocyclyl R? selected from the group consisting of lower alkyl hydrogen (lower alkoxy | © lower alkoxy lower alkyl FeO alkylthio lower alkoxy lower alkyl lower alkylsulphonyl lower alkoxy phenyl phenyl alkyl Jud low alkyl phenyl low alkyl phenyl lower alkoxy phenyl alkylene dioxy lower phenyl Jad lower alkyl phenyl lower alkyl — phenyl - alkyl > lower Jui alkylene dioxy JS - lower phenyl lower calky heterocyclyl heterocyclic ring and lower alkyl heterocyclic ring 'lower alky' JR selecting it from the group consisting of lower alkyl lower alkoxy lower alkoxy formyl halo—halo alkyl dower alky addi a ~hydroxy low alkyl—amino sil lower alky JS -A-CH,O "lower alky" - Vo tmtmtv)-0.-..0n and ThO-attie).mmt)-” 5¢-(CH;)-O-(CR*R®),NH, tq)-0-Lytn)-

+ RRS is chosen from the group consisting of a lower alkoxy chydrogen and <halogen (pa sila j) is chosen from the group consisting of a chetrocyclyl phenyl “Jud” heterocycle phenyl substited with a group chosen from the group consisting of a Jaweralky | lower alkoxy doser and two halogens R? and RY where each is a hydrogen or a lower alkyl talky A is catalized ) = tKetalized 1,2-dihydroxy ethylene Y chosen from the group consisting of -0-(02)0- NH (CO)NH and NHC(0)-O- ys “ is equal to OY or ; and m is equal to zero or 1. Compounds of formula 1 inhibit binding to endothelin Therefore, it is useful in the treatment of disorders associated with vasoconstriction, such as high blood pressure and coronary disorders. Vo Detailed description: This invention relates to new sulphonamides and their use as medicines. On the face of pa pail, this invention relates to new compounds with the formula: I kg RY 501 N . R? - \ 0 RS N — Yo R7 at takh Since R! is a thetrocyclyl heterocyclic 8, R? is chosen from the group consisting of a low alkyl chydrogen lower “alkyl lower alkoxy lower alkylthio lower alkoxy Wo

and JI - lower alkoxy lower alkoxy Lower alkylsulphonyl lower alkoxy lower aiky phenyl lower alkoxy; Low Alkyl Dioxyphenyl Low Alkyl-Phenyl; alkoxyphenyl-low alkyl alkylene dioxy lower phenyl - lower alkyl (isi calky© hetrocyclyl heterocyclic and heterocycle low alkyl :101776; 13 are selected from the set consisting of a low alkyl cower alkyl: ©1097 formyl halo-low alkyl chalo- lower hydroxy-lower alkyl amino-alkyl camino lower alky adil a Low alkyl A- ¢-(CHp)m-O-(CR*R®),NH; ¢-(CH,)p-O-(CR*R"),-OR' 5 "-(CH,)m-O- (CR'R"), OH "CH,0-A 0 and -(CHy)m-O-(CR'R®),-Y-R® are each chosen from the group consisting of A lower alkoxy chydrogen and a chalogen R® is selected from the group consisting of a heterocyclyl ring “phenyl” and a phenyl substited with a group that is selected from the group that Consists of a lower alkyl \o a lower alkoxy and a halogen (60p18108; RY is each hydrogen or a slower alkyl A is catalized =F ) dihydroxy-ethylene; Ketalized 1,2-dihydroxy ethylene 57 is selected from the group consisting of NH(C(O)NH -0 (C(O)NH- —OC(0)-0- 5 .NHC(0) -O- A A Y. “is equal to A” or ;; and m is equal to zero or done and the term: “lower as used here iad for a group with a number of 1 to 7 carbon atoms Preferably from 1 to 1 carbon atoms, and alkyl groups alkoxy JS thio alkylthio in addition to alkyl groups GAS from alkanoyl groups Yo can be linear or branched The methyl cmethyl groups cethyl propyl isopropyl butyl and the secondary and tertiary butyl butyl groups are examples of alkyl groups

: 0

this alkyl. And halogen refers to fluorine, cfluorine, chlorine, bromine, iodine, dodine, preferably chlorine, and lower phenyl Jib alkylene dioxy, for example; It is a dioxyphenyl ethylene moiety, p160. and the kitalized AY) hydroxyethylene group ¢Ketalized 1,2-dihydroxy ethylene is formed eg (JE 0 is the ?; 2-dimethyl- .1,3-dioxolan-4,5-diyl and examples of heterocyclic derivatives are mainly monocyclic and dicyclic which are mono- or di-substituted »for example by a lower alkyl Alkanoyl is a low-dower alkanoyl halogen or with an additional heterocyclic moiety or these rings can be unsubstituted and contain coXygen nitrogen or 0 sulfur as a chetro atom such as -17 and ?- furyl ofuryl pyrimidinyl “pyrimidinyl” —Y ?- and 4-pyridyl -1-1 2-3-d-pyridyl 1 4-diazinyl and 1,4-diazinyl -¢1,2 morpholino —Y morpholino and —Y-thienyl and 3-thienyl -2 isoxazolyl 0201 oxazolyl chloride “E” thiazolyl cthiazolyl imidazolyl 010820171 pyrrolyl ptzofuranyl cbenzofuranyl benzoquinyl <benzothienyl indolyl <indolyl purinyl ¢purinyl quinolyl 10 isoquinolyl and quinazolyl .Examples of 18 hetrocyelyl heterocyclic moieties are in particular pyridyl ¢pyrimidinyl thienyl and isoxazolyl substituted and unsubstituted. Examples of R heterocyclic moieties include in particular pyrimidinyl and morpholino. Examples of unsubstituted R The homolog RY includes

fury] and ferryl pyrimiding] pyrimidyl and in particular pyridyl Yo “monocyclic Preferred compounds of Formula 1 are those in which an O-hetrocyclyl ring and/or an oxygen as part of the non-ring ©! The ON congener contains 8-nitrogen sulfur cisoxazolyl isoxazolyl pyrimidinyl pyridyl and in particular pyridyl dower alky which is unsubstituted or reduced alkyl thienyl or thienyl furyl furyl mono- or di-lower- (addi a amino Js mono 0 di “amino amino halogen halogen © 1) Also, there are preferred compounds of the formula dower alkanoyl or alkykamino

in which R? is a chydrogen cpyrimidinyl pyridyl pyridyl morpholino ¢ihiomorpholino pyridino 6:m; pyrrolidino mtl777011; benzodioxolyl “< benzodioxolyl lower alkyl phenyl or lower alkylthio and those RY Led are “O-(R*R”),0H and 07 03)-0-R © The 5-O-(CHy)-Y-R® 8" radical is a N monocyclic ring and/or heterocyclic radical containing coxygen and in particular pyridyl pyrazinyl or furyl furyl There is particular interest in compounds of formula 1 in which RY is a pyridyl moiety substituted for a low alkyl R? lower alky is a morpholino R? “morpholino is a moiety - RY.O(CH,),0C(ONHR® 0) is a lower alkoxy and 858 is a hydrogen and the preferred moieties are heterocyclic chetrocyelyl moieties. In particular pyridyl residues such as 1-pyridyl 2-pyridyl The compounds of Formula 1 above are endothelin-receptor inhibitors and therefore can be used in the treatment of disorders associated with endothelin activities Vo, in particular, disorders of the circulatory system, such as high blood pressure, pall, “pressre,” ischaemia, vasospasm, and angina pectoris (Ka). which has the formula LST as follows: ' a) a complex reaction with the formula: 7 : RY 5 11 11011 N WE N = Hal R8 RT Yo. where both !8 have 82 ; and 85-8 have the aforementioned meanings, and Hal is a halogen, or Yo

With a compound of the formula: HO (CR*R%), XH where en 82 "8 has the aforementioned meanings and X represents © or (NH : ° b) a compound reaction of which Formula: RS [II 4p Q N RZ - \ 0 RS N = Vo R? R® RT wherein “82-8 has the aforementioned meaning above; With a compound having the formula: Ye 1507 where AIR! is the aforementioned meaning above and where Q stands for halogen and 7 ih amino or © stands for 7 amino stands for halogen < halogen or C a complex reaction with the formula: RISO,NH RY RS Iv N v. Rr? — \ 0 RE N = t cat (Hm tamh) where both (R*R® (R? (R! R! thel) X R® se have the aforementioned meanings wel :

-c 1) with isocyanate of formula 897100 or carbamoyl chloride of formula dua 78000 “8” has the aforementioned meaning; or c?) with phosgene and then with an alcohol of the formula RPOH or with chloroformate of the formula for ©00(0(0)"; or .o 2) a compound reaction of formula 1 where R? is halo-lower alky with a compound of the formula HOCH,- A- lower alky : where A is Ketalized 1,7-dihydroxy 'Ketalized1,2-dihydroxy ethylene all' and if There is a desire; the substituents in the resulting compound of formula 1 are modified and/or 0 converted into a salt of the compound of formula 1 obtained.In the reaction of a compound of formula IT with a compound of formula 0878.301(110) this compound is traditionally used as alcohols alcoholate an alkali metal The corresponding glycol or sind analogue aminoalcohol such as ethylene glycol or sud caminoethanol when n = 7 is used as a solvent Preferably alcohols The alkali metal alcoholate is a sodium alcoholate. mono salt of ethylene flavor; propylene or butylene glycol or camino-ethanol propanol or butanol J ssn Reaction of a compound of formula [11] can be carried out with a compound of formula RISO; Z using a method known by itself, Yo, to manufacture sulphonamides, in an inert organic solvent such as dimethyl sulphoxide, with heating or in a gaseous atmosphere for protection; This is under the argon, for example. The reaction can be carried out according to variable C1) by a method known by itself in the preparation of carbamates 465 and ureas from alcohols and amines and so on; Kay converts Yo of a compound of formula IV to a compound of formula 1 in which 7 is —OC(ONH-) using isocyanate of formula 27100 in a suitable anhydrous organic solvent; for example: zYo

–q— | Jie hydrocarbon, toluene, with heating. An isocyanate can be generated in the reaction medium; For example, an azide of the formula ROCON; is pyrolyzed. Jilly compounds of formula 1 can be obtained using Y=NHC(O)NH- by using compounds of formula IV in which B is NH 0 and depending on the variable c7); It is possible to react a compound of the formula Led IV 7 forming oxygen with phosgene and accordingly with an alcohol of the formula 82011 to give a compound of the formula A in which A is a (Sa) moiety.—0C(0)- 0- Using a phosgene salt such as ALS phosgene (C1-COOCCl;) diphosgene or triphosgene NA (CO(OCCI3), triphosgene) from phosgene compounds of formula 1 are obtained with Y-NHC(0)-O- being similarly starting 0 of compounds of formula IV with NH=Y being NH=Y phosgene is usually used as a solution in an inert anhydrous organic solvent; Jie hydrocarbon Jie hydrocarbon toluene The reaction with phosgene can be carried out at room temperature The acid chloride 53 obtained as an intermediate is reacted with alcohol 87011 easily while heating The reaction can be carried out according to the process Variable d) Under the conditions of the reaction described in the process of variable a) Yo, which produces a compound of formula 1 where 1 * 3 is a low alkyl moiety A-CHy-O- lower-alkyl. The substituents in the compound of formula T can be modified. which is obtained in this way. And therefore; The methyl group of RY can be converted to a formyl group by oxidation. Oxidation can be carried out in a manner known by itself; For example, by means of selenium dioxide, the formyl group obtained in this way can be reduced to a hydroxymethyl group '0', and this reduction can be carried out in a manner known by itself; For example by using a reducing agent Jie NaBH; the J} hydroxymethyl group can be converted to a halo = halo- methyl group by reacting with a halogenation agent such as PCl5 lai » The POCl; 17-heterocycle Jie hetrocyclyl pyridile moieties can be oxidized to b oxides 0:108. All of these interactions can be carried out according to self-known methods. Compounds of formula 1 with a YO method known by itself can be converted into asalts such as alkaline salts such as sodium and potassium salts or alkaline earth metal salts such as calcium or magnesium salts.

-1.- Compounds used as starting materials; which are not known or whose preparation is not described hereinafter; They may be prepared by methods similar to known methods or by methods described in more detail later. For compounds having formula 1 on inhibitory activity receptors the inhibitory activity can be determined using the test methods described below: endothelin with receptors Incorporated M51 endothelin Inhibition of endothelin binding: 1 ° pertaining to human M21 receptor (cDNA) complementary DNA piece placed

M.Adachi, Y-Yang, Y. Furuichi and C. Miyamoto, BBRC 180,1265-1272 Insects. Baculovirus insect cells are centrifuged in a baculovirus cell system

Vo infected with baculovirus 080010108 from fermentation unit 231 (0000?* gravity; 1 hour of infection; then resuspended in Tris 01 buffer; 0°C) after AREY 0 and centrifuged (MeCly) mmol of magnesium chloride 1 0.4 mmol; pH value (©) Tris central again. After resuspension and centrifugation, the cells are suspended in 8060 ml of the same buffer solution and then lyophilized at 170 °C. Cells are lysed when the suspension is dissolved in this low osmosis mixture. After repeated freeze/melt drying, a minute is made; 4" m). After suspension in a solution of 11 G; YOu + 4) homogenization of the suspension and centrifugation Vo

You mmol; magnesium chloride; YO mmol; pH value 7.4; VO) Regulator Tris Approximately 3.9 mg/protein ml (protein content 1 mmol sucrose) Equal parts are stored at -d/tm (Ja) To carry out the binding experiment, the lyophilized membrane preparations are melted; after centrifugation for minutes, the suspension is resuspended in the experimental buffer 01 gravity for Youu at 10"C and at 0 mmol of YO Contains Vi regulator; pH value Tris 01 mmol (bovine serum albumin) bovine serum albumin 7.0 EDTA 1 mmol MnCl; manganese chloride µg protein Vo 1 μl of this membrane suspension containing 001 mL persaturated iodine is incubated with 1H00”-]”12 (endothelin activity 0 μl of endothelin with protein 71 final concentration copm You) mol) in the experimental buffer solution foi 1700 Siemens To 1 μl of the experimental buffer containing different concentrations of compound 001 and (PM bicarmol)

-11- | The test. Incubation is carried out at 2°C for 2 hours or at *C for 2 hours. elu Separation of free and membrane-bound ligands containing radioactive iodine is performed by filtration on a glass fiber filter. The inhibition activity of the compounds of formula [1] which were determined in this way are mentioned in Table 1 © Jia The value of (ICsp) i.e. the concentration [in nanomoles [nM] required to inhibit 750 percent of the specific binding of endothelin Iodized. Radioactive. Table 1 oY vs vf 51". Inactivation of endothelin-activated concentrations in dissociated rings of mouse aorta. rat aorta rings. 01 rings were cut to a length of © mm. From the aorta of the neck region of adult Wistar-Kyooto rats, the lining of this blood vessel was removed by scraping the inner surface.Each annulus was dipped at ambient temperature in 0 mL of Krebs-Henselet solution. Henseleit in a separator bath with the addition of 745 0 oxygen and 75 0 carbon dioxide COp. The rate of regeneration of the rings was measured. The rings were stretched to a prestrain “g. After incubation for 10 minutes with Vo compound. The test or the load were added cumulative doses of endothelin 1. The amount of activity of the test compound was confirmed by the observed shift to the right of the dose-activity curve of endothelin VT in the presence of different concentrations of the antagonist. This shift to the right (or dud dose "(DR) corresponds to the ECsp ard for endothelin-1 in the presence and in the absence of the antagonist; with the BCsp value denoting the required endothelin concentration to half-maximal concentration. : YS and has The corresponding PA value, which is a measure of the activity of the test compound” was measured using a computer program according to the following formula from “dose ratio” 118 for each Ae jal activity curve) 2 - log = (DR-1) Log (antibody concentration) The ECsp value for endothelin in the absence of test compounds is oF nanomoles.

-11- | The values of PA2 obtained using the compounds of formula 1 are shown in the table? Table 1: Nin Lam 51 | 4 On the basis of the ability of these compounds to inhibit binding with endothelin, o _ compounds of formula 1 can be used as drugs to treat disorders related to vasoconstriction AB on these disorders include high blood pressure, coronary artery disorders coronary disorders “cardiac insufficiency”; renal insufficiency 8021 renal leakage 58 . Blood retention in the brain Cerebral ischaemia Localized death in the brain Cerebral infact 0 Migraine cmigraine Bleeding in the brain subarachnoid faemorrhage Raynaud’s syndrome aynaud syndrone and high lung pressure fasted. Lad can use these compounds in the treatment of coronary artery sclerosis (catherosclerosis) with re-stenosis after dilation of blood vessels by a drain; infections; ulcers of the stomach and duodenum “duodenal ulcers” ulcus coruris Bacterial poisoning of the blood with types of Gram-negative bacteria; shock glomerulonephritis “glomerulonephtritis 0 suggest the colic kidney”; glaucoma, asthma, and in the treatment and prevention of complications from diabetes and complications from cyclosporin administration, in addition to other disorders associated with endothelin activity. Compounds of formula 1 can be administered rectally by AIL. ; by injection; eg by intravenous injection; intramuscularly Under the skin; in the bursa or across the skin; or under the tongue or in the form of eye preparations; or in the form of sprinklers. capsules; tablets, suspensions or solutions for oral administration; dresses; Solutions taken by ial), eye drops, sachets, or spray solutions are examples of administration forms.

1©- | and intravenous administration; Intramuscular or oral form is preferred. It is considered a preferred type and the dose to be administered that contains the compound of formula 1 in significant amounts depends on the nature of the chil, the age, the requirements of the patient and the mode of administration. In general; The dose can range from about 100-1100 mg/kg body weight per day. © Preparations containing the compounds of formula 1 may contain inactive additives or pharmaceutically active additives. Tablets or granules may contain, for example, a series of binding compounds; filling compounds; carriers or thinners. Liquid preparations can be available in the form of a water-miscible solution; The capsules may contain a filling or thickening compound in addition to the active ingredient. In addition JY; oli taste-enhancing additives such as in addition to; those of pall used sale 0 as preservatives; fixing materials; moisture retainers and emulsifying agents as well as salts to alter the osmotic pressure; Buffering solutions and other additives may also be present. The aforementioned carriers and the aforementioned thinners may also contain organic or inorganic substances such as water; Gelatin, lactose dJactose, starch, magnesium stearate, 8, that is calc, gum arabic, gum arabic, polyalkylene glycolate, Vo, and so on. Of course, all carriers used in the manufacture of lotions are non-toxic. The following examples illustrate the invention in more detail. Example 1 Dissolve 1.74 grams of sodium in 0 * ml of ethylene glycol at a temperature of 0 #C. Then ¥ al ja was added from 5-tert-butyl-thiophene-2-sulphonic acid 6-chloro-5-0 (2-methoxy-phenoxy)-2,2-bipyrimidin-4-ylamide | 0 a part at the same temperature and heat the mixture at 100°C for ; hours and a half. Pour the clear reaction solution on a solution of ice / adda 106 / dilute hydrochloric acid 1161 and then extract the mixture three times by YY + ethyl acetate each time. Jue the organic phase was cell three times then dried on sodium sulphate Yo and finally evaporated on a rotary evaporator. It was then obtained

-Vé- l 5-tert-Butyl-thiophene-2-sulphonic acid 6-(2-hydroxy-ethoxy) _5-(2-methoxy-phenoxy)- 2,2'-bipyriniidin-4-ylamide In the form of a yellow foamy substance. Mass Spectrum 497 (M-S0y) Preparation of starting compound o {dissolve 1 gram of 0--butyl-thiophene-7-sulfonyl chloride 5-tert-butyl-thiophene-2- sulphonyl chloride in yo ml ethanol at room temperature; Then it was treated with 0 ml of 775 ammonia solution and heated by reflux for ; hours and a half. The mixture was concentrated on a circulating evaporator and the precipitate was treated with water; then extracted by ethyl acetate (YO + acetate ml); The drying was carried out on magnesium sulphate and the concentration was again 0 on a rotary evaporator, after which O = tert-butyl-7-thiophene-7-sulfonamide -5-tert-butyl-thiophene-2- was obtained. sulphonyl chloride as white crystals. Mass spectrum: (JM) 715 and then the potassium salt was obtained by means of K tert.-butylate in methanol.methanol: b) 0.49 g of 4 was dissolved; BT chloro-*-(7-methoxy-phenoxy)-?; ( 5-tert-butyl-thiophene-2- sulphonamide) was added at room temperature and the solution was then stirred at room temperature for 1 hour. After that, it was treated with 0.785 grams of potassium (* (©-tert-butyl-thiophene-?-0 sulfonamide) for the reaction at room temperature for an additional two hours.Yor ml water and then Yoo ml ether were added to the reaction mixture with vigorous stirring to form a white crystalline precipitate and then filtered by vacuum The crystals were suspended in aqueous dilute hydrochloric acid, stirred at room temperature for half an hour, filtered by vacuum, and dried under high vacuum, after which 5-tert-butyl-thiophene-2-sulphonic acid 6-chloro-5 was obtained. -(2-0 ‎methoxy-phenoxy)-2,2'-bipyrirnidin-4-ylamide =~ Yo as a white crystalline solid.Mass spectrum: 877.4 (M+H)Yo

—Vo—

Y Example A solution of 7.17 grams of 5-tert-butyl-thiophene-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2 is heated '- bipyrimidin-4-ylamide 1 and 2-pyridyl carboxylic azide g of ?- pyridyl carboxylic acid azide 1/9 ee © +) toluene in toluene P-dimethyl amino pyridine (nu mg of para-dimethylamino on a rotary evaporator and then sectioned toluene at a temperature of 80 C for two hours.Toluene was removed (Ja m from 1 L acid) and a solution of 8) methylene chloride precipitated between two methylene chlorides. magnesium L) and the organic phase was dried on magnesium sulfate (TO) HCL hydrochloric and the solvent was finally removed at a rotary evaporator. The crude product was separated by methylene sulphate chromatography using methylene chloride/methanol gel on chromatographed eluting gel. Then (1/*) chloride/MeOH pyridin-2-ylcarbamic acid 2-[6-(5-tert-butyl-thiophen-2-ylsulphonylamino)-5-(2-methoxy- phenoxy)-2 was obtained. 2'-bipyrimidin-4-yloxy]-ethyl ester methylene as a pale yellow solid that was recrystallized from Vo .chloride/MeOH (MHH)" Mass spectrum: 178.7 eg? at °C ethanolamine in ?mL of ethanolamine sodium ¥1 mg of sodium 050 mg of sodium was dissolved in parts at the same temperature by dalled and then the compound from example 1; section (B); Then the solution was pulverized at a temperature of 100"C for a period of hours. After that, by means of a ¥ M solution of 1 N acid, the mixture was poured into ice water, then it was adjusted to a pH of 1101 hydrochloric, and after that it was separated. A pale yellow crystalline solid that was filtered by vacuum, then washed with water and dried under vacuum, thus obtaining 5.tert-butyl-thiophene-2-sulphonic acid 6-(2-amino-ethoxy)-5- (2-methoxy-phenoxy)-2,2-Yo bipyrimidin-4-ylamide

1h© as yellow crystals. Mass spectrum: 4.6 ft. Example ; 0 ad milligrams of 5-tert-butyl-thiophene-2-sulphonic acid 6-(2-amino-ethoxy)-5-(2- methoxy-phenoxy)-2,2-bipyrimidin-4-ylamide ~~ © in 01 ml of toluene, and it was treated with OF 1 mg of 7-pyridylcarboxylic acid azide, then we will heat the solution at WY temperature for ; hours. The toluene was removed by a rotary evaporator and the precipitate was fractionated between ethyl acetate and water. The organic phase was dried on magnesium sulphate and then concentrated at a rotary evaporator. The precipitate was separated by 0 chromatographed on silica gel using methyl chloride/methanol (1/1) chioride/methanol for eluting. Then 5-tert-butyl-thiophen-2-sulphonic was obtained. acid 5-(2-methoxy-phenoxy)-6-[2-(3-pyridin-2-yl-ureido)- ‎ethoxy]-2,2'-bipyrimidin-4-ylamide as a crystalline solid. Mass 797.4 (MH) yo Example o 7 mg of sodium hydride (NaH) (£70) at room temperature is added to a solution of 1 mg of 4-amino-6 -methoxy-5-(2-methoxy-phenoxy)-2,2"-bipyrimidine in 10 mL of tetrahydrofuran ©80870:050:2; QB solution at room temperature for 1.5 hours and then added 167.8 mg of 5-tert-butyl-thiophene-2-sulphonyl chloride at the same temperature Yo. The mixture was stirred at room temperature for another two hours; then poured over ice water and extracted by means of cethyl acetate acetate, then the acid of the aqueous phase and extracted using methylene chloride. The organic phases collected were dried on magnesium sulphate and concentrated on a rotary evaporator. The precipitate was separated by chromatography on silica gel using methylene chloride / methanol. (V/Y +) methylene chloride/methanol | Yo to elude. z We is obtained

1 5-tert-Butyl-N-[6-methoxy-5 _(2-niethoxy-phenoxy)-2,2-bipyrimidin-4-y1] -thiophene-2- sulphonamide (M-80,) 477 as yellow powder . Mass spectrum: preparation of starting compounds (order 4,6-dichloro-5-(2-methoxy-phenoxy)-2,2"-bipyrimidine 7.04 g of { © commented at ammonia ml of ammonia VO + methanol ml of methanol YO EP 5771604) at 75 °C using a feeding tube. The reaction mixture was left at room temperature overnight and then concentrated under vacuum. It was washed with water The precipitate was partitioned between a small amount of water and methylene sodium (ml).The organic phase was dried over sodium sulfate (© +) methylene chloride chloride, and the resulting solid was separated, then the remaining ether with ether (jase) was concentrated at a rotary evaporator. sulphate 0 4-amino-6-chloro-5-(2-methoxy-phenoxy)-2, 2- was dried under vacuum and bipyrimidine was obtained.

LM 374 as an almost white fine powder. Mass spectrum: At room temperature to sodium methylate b add 5 g of sodium methylate ml of 001 in 4-amino-6-chloro-5-(2-methoxy-phenoxy)-2, 2'-bipyrimidine solution of Yo h. The methanol was removed on FY and then the solution was heated by reflux for 1 mm methanol and washed with methylene chloride solution precipitated at a methylene chloride al rotary evaporator; Then, the organic phase was dried on magnesium sulfate; Then, hydrochloric acid from hydrochloric acid was finally removed from the solvent under vacuum. The crude product was separated by chromatography on silica gel for eluting. (1/0) was obtained using a mixture of methylene chloride/methanol 0 4-Amino-6-tnethoxy-5-(2-methoxy-phenoxy)-2,2'-bipyrimidine (04.04) as a yellow powder. Lemony Mass spectrum K7 > Example | and sodium glycolate in a manner identical to that of Example 1; and of sodium glycolate 5-pentyl-thiophene-2-sulphonic acid 6-chloro-5-(2-methoxy -phenoxy)-2,2"-bipyrimidin-4-Yoylamide oe

M 1, 5-pentyl-thiophene-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2'- bipyrimidin-4-ylamide was obtained. A white solid. Mass spectrum 976.7 (MH)° Preparation of starting compounds Z ( The compound 5-n-pentyl-thiophene-2-sulphonicacid was obtained from 2-pentyl-5-(t-butylsulphonamido) thiophene (EP 75 2) with ethanol [ethanol] a concentrated solution of hydrochloric acid and salt formation by means of potassium tri-butylate.methanol: Ve b) by Alles method of what Mentioned in Example 1; Section (b) of the reaction *-Norpentyl-thiophene-?"-sulfonamide potassium 4,6-dichloro-5-(2-methoxy- s (5-n-pentyl-thiophene-2-) sulphonamide) K phenoxy)-2,2'-bipyrimidine 5-pentyl-thiophene-2-sulphonic acid 6-chloro-5-(2-methoxy-phenoxy)- 2,2 was obtained -bipyrimidin-4-ylamide yo as a white solid. Mass spectrum: (M) oto Example 17 In a manner similar to that in Example 7 Who? -6-2 5-pentyl-thiophene-2-sulphonic acid (hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2-bipyrimidin-4-ylamide pyridin- 2-ylcarbamic acid 2-[5-(2-methoxy-phenoxy)-6-(5-pentyl- ‎thiophen-2-ylsulphonylamino)-2,2"-bipyritnidin-4-yloxy]-ethyl ester 00 as an additive White solid Mass spectrum 97.4 (M+H) Example A In the same way as Example ¢F From sodium glycolate and 5-(2,2-dimethyl- propionyl)-thiophene-2-sulphonicacid 6-chloro-5-(2-methoxy-phenoxy)- 2,2'-bipyrimidin-4-ylamide Yo oe was obtained.

-1- 5-(2,2-dimethyl-propionyl)-thiophene-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-metnoxy-phenoxy)-2,2-bipyrimidin-d-y lamide

As a crimson powder Mass spectrum: (M+H) oATY Preparation of starting compound 0 in a manner similar to that mentioned in Example 1; section (b) of the reaction of the potassium salt of compound 5-(2,2-dimetylpropanoyl) thiophene-2-sulphonamide : (Preparation: .06 » Org. 1 vol 07 p.47710) and 4,6-dichloro-5-( 2-methoxy-phenoxy)-2,2'- bipyrimidine, 2-dimethyl-propioriyl)-thiophene-2-sulphonic acid 6-chloro-5-(2-methoxy-phenoxy)-2, 2- 0,2(-5 bipyrimidin-4- ylamide as a crystalline solid. Mass spectrum: ).07 (MHH) The potassium salt of this compound was obtained by potassium tert.-butylate in sili methanol. yo Example 9 in a manner similar to that in Example oF of 7-pyridylearboxylic acid pyridylearboxylic azide 5-(2,2-dimethyl-propionyl)-thiophene-2-sulphonic acid 6-(2-hydroxy- acid azide (ethoxy)-5-(2-methoxy-phenoxy)-2,2'-bipyrimidin-4-ylamide The desired compound pyridin-2-ylcarbamic acod 2-[6-[5-] was obtained. (2, 2-dimethylpropionyl)-thiopnen-2-ylsulphonylamino | 01 [-5-(2-methoxy-phenoxy))- 2,2'-bipyrimidin-4-yloxy]-ethyl ester: As a beige powder. Mass spectrum 4.7 (M+H) V+ Example 01 Dissolve 0 g of sodium in 71 mL of Gadd ethylene glycol at YO temperature 00% a. After cally add 4 grams of 5-isopropyl-pyridine-2-sulphonic acid 6-chloro-5- (2-methoxy-phenoxy)-2,2'-bipyrimidin-4-ylamide We

Simmer part by part at the same temperature, then heat the mixture to a temperature of 100*C for ; hours. Pour the clear reaction solution into 100 mL of water; Then the pH was adjusted for 1 with a 'N' solution of hydrochloric acid; The separated yellow crystals were then vacuum filtered and washed with water; Then with ether and finally dried under high vacuum. Thus, 5-isopropyl-pyridine-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2'- | 2 bipyrimidin-4-ylamide sales is a yellow crystalline solid. Mass spectrum: (M-H) 0.579 (M-H) Preparation of Starting Compounds a) 4 g S-isopropylpyridine-2-sulphonamidecss were dissolved in 0 ml of methanol (MeOH) after which 7.308 g of tert-butylated was added Potassium 1.1218 at room temperature and then the solution was stirred for another 71 minutes.After that, the whole concentrate was placed on a rotary evaporator and then Cia the potassium salt thus obtained under high vacuum. b Dissolve 4 g of 4,6-dichloro-5-(2-methoxy-phenoxy)-2,2"-bipyrimidine in #11 mL of dimethyl sulfoxide; add 0.7 g of potassium (* (S-isopropyl-pyridine-2-sulphonamide) K at room temperature and then stop the solution at room temperature for 10 hours. Vor ml of water and 96 ml ether with vigorous stirring, the pH of the solution was adjusted to 1 by adding a ?NM solution of hydrochloric acid.The white crystalline precipitate was filtered under vacuum and then washed with water, then with ether and then the crystals were suspended in a dilute aqueous hydrochloric acid solution (Ve) mL of water and OR 0.0 mL of 1 N hydrochloric acid) and stirred for ¾ minutes; Then it was filtered with vacuum, washed again with water, and dried under high vacuum. Accordingly, 5-isopropyl- pyridine-2-sulphonic acid 6-chloro-5-(2-methoxy-phenoxy)-2,2"-bipyrimidin-4-ylamide was obtained as a white crystalline solid. Mass: ¥ ,)00 (M-11) ex 11 Yo solvent ? grams of 5-isopropyl-pyridine-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2 -methoxy- phenoxy)-2,2-bipyrimidin-4-ylamide in 40 ml of toluene and then treated by 0,1 110°

—yy— Then heat the solution after 2-pyridylcarboxylic acid azide —Y grams of ed JN at a temperature of 2°30 for a period of hours. Subsequently the concentrate was concentrated on a rotary evaporator and a titre fraction of hydrochloric acid and ethyl acetate: the organic phase was dried on 1 bean of magnesium sulfate solution; Then the solvent was removed under vacuum, and the precipitate was separated by chromatography on [2-]6-5- silicagel using methylene chloride/methanol (10?/10) eluting. Subsequently, © isopropyl-pyridin-2-ylsulphonylamino)-5-(2-methoxy-phenoxy)-2, 2"-bipyrimidin-4-yloxy]-ethyl (M+H) 1597, was obtained as yellow crystals Colour.Mass spectrum: ester methylene The compound was dissolved in methylene cdihydrochloride to prepare dihydrochloride in hydrogen chloride and treated with an identical amount of ,4 N of hydrogen chloride at room temperature. On a rotary evaporator, then the substance ethanol 0 ethanol was separated at a temperature of 10’C for £ hours. The separated crystalline solid was then dried under vacuum.

VY Example 5-isopropyl-pyridine-2-sulphonic acid 6-(2-amino- in a similar way to example 4; from ethoxy)-S-(2-methoxy-phenoxy) -2, 2- bipyrimidin-4-ylamide 2-pyridylcarboxylic acid azide and 7-pyridylcarboxylic acid azide were obtained Vo 5-isopropyl-pyridine-2-sulphonic acid 5-(2-methoxy-phenoxy)-6-[2 -(3-pyridin- of interest 2-yl-ureido)-ethoxy]-2,2"-bipyrimidin-4-ylamide (M-H) 87, as yellow crystals. Mass spectrum: Starting compound obtained. In a manner similar to that stated in Example * of ethanolamine and the resulting compound (MH) OFA, section (b) as yellow foam Mass spectrum: 01 eg pe 0 e: 11 eg pyridine-2- sulphonic acid 6-chloro-5-(2-) and using “01” in a manner similar to what was mentioned in the example, ethylene glycol (18 methoxy-phenoxy)-2,2"-bipyrimidin-4-ylamide pyridine-2-sulphonic acid 6-(2-hychloroxy-ethoxy)-5-(2-methoxy-phenoxy)- {(M-H)11,46 as white crystals. Mass spectrum: 2 2'- bipyrimidin-4-ylamide Yo preparation of initiation compounds

Al { dissolve 11 grams of ?- pyridyl sulfonyl chloride J.

Org. 2-pyridylsulphonyl chloride chem. vol 0% pg (PAR) in Vo ml ethanol; then 0 ml of ammonia solution 7 was added with ice cooling, then the mixture was heated by reflux for a period of hours, after which the reaction solution was concentrated On a rotary evaporator, the precipitate was fractionated between ethyl acetate and water, the organic phase was dried on magnesium sulfate and finally concentrated on a rotary evaporator. -11.The potassium salt was obtained by using butyl tripotassium in methanol B in a manner similar to that mentioned in Example 0 Ab, and by the reaction of (2-pyridylsulphonamide)-K 4,6-dichloro-5-(2- methoxy-phenoxy)-2, 2'-bipyrimidine pyridine- 2-sulphonic acid 6-chloro-5-(2-methoxy-phenoxy)-2,2'-bipyrimidin-4-ylamide | 0 as white crystals. Mass spectrum: 498.7 (M-H) Example VE: In a manner similar to that mentioned in the example of oY and from pyridine-2-sulphonic acid 6-(2-hydroxy-ethoxy)- 5-(2-methoxy-phenoxy)- 2,2' —bipyr- imidine-4-ylamide Yo in 2-pyridylcarboxylic acid azide pyridin-2-ylcarb- amicacid2-[ 5-(2-methoxy-phenoxy)-6-pyridin-2-Isulphonylamino)-2, 2'-bipyrimidi n-4-yl oxy J-ethyl ester as white crystals. Mass spectrum: 616.4 ( M-H) e.g. Yo z Ye. in the same way as in Ex. 01 using pyridine-3-sulphonic acid 6-chloro-5-(2- methoxy-phenoxy)-2,2" -bipyrimidin-4-ylamide and ethylene glycol were obtained -2(-6 pyridine-3-sulphonic acid hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2' -bipyrimidin-4-ylainide as white asparts. Mass spectrum: 497 00. Yo Preparation of starting compounds

except a) in a manner similar to that in the OT example (a); and of *- pyridylsulfonyl chloride-3 (Chen.) pyridyisuiphonyi chioride .1.08 vol 4 5; Page 784) and ammonia, 2-pyridylsulphonamide was obtained as a white crystalline solid, and potassium salt was obtained from it by using potassium tert-butylate in © methatol.potassium tert.-butylate in methanol b) in a manner similar to that in Example 01 subsection (b); By the reaction of (©-pyridyl-sulfonamide) (3-pyridylsulphonamide)-K a soli so and -2'4,6-dichloro-5-(2-methoxy-phenoxy)-2, bipyrimidine 28 was obtained The desired compound contains pyridine-3-sulphonic acid 6-chloro-5-(2- ‎methoxy-phenoxy) -2,2'-bipyrinridin-4-ylamide 0 01 as white crystals. Mass spectrum: (MM) 4716 Ex 11 in a manner similar to that in Ex 11; and of pyridine-3-sulphonic acid 6-(2-hydroxy- ethoxy)-5-(2-methoxy- phenoxy)-2,2'-bipyrimidin-4-ylamide and 2-pyridylcarboxylic acid azide 38 pyridin-2-ylcarbamicacid2-[5-(2- methoxy-phenoxy)-6-pyridin was obtained -3-ylsulphonylamino)-2,2"-bipyrimidin-4-yloxy]-ethyl ester 0 as white crystals Mass spectrum: (M-H) 19,4 Ex 11 solute 701 mg 6-[2 -(tert-butyl-dimethyl-silanoxy)-ethoxy]-5-(2-chloro-5-methoxy- phenoxy)-pyrimidin-4-ylamine in Yo ml of tetrahydrofuran, then done 0 Treated at room temperature with 7 mg of sodium hydride NaH (10) 6 and then stirred at room temperature for 2 hours, then 1.00 mg of O=butyl-tri-thiophene-"-sulfonyl chloride mm mm 5 was added -tert-butyl-thiophene-2-sulphonyl part by part The solution was stirred at room temperature for another two hours, then poured into ice water and extracted twice with a total amount of You ml of ethyl acetate After the conventional work; on the organic phase; The crude silyl-protected Yo product was separated onto silicagel by a mixture of methylene chloride/miethylene (V/A) chloride/ethy! acetate as the eluting solvent. Yo 1

The obtained brown foam substance 719 (mg) was dissolved in 15 ml acetonitrile then Gale at room temperature by 1.0 ml hydrogen fluoride solution (7240) and stirred for two hours. The reaction mixture was fractionated between ethyl acetate and a half-saturated solution of sodium chloride and then the organic phase was worked on conventionally. The crude product © was separated on silicagel by methylene chloride/ethyl acetate (;/1) as eluting solvent and recrystallized from ether/hexane. Thus, 5-tert-butyl-thiophene-2-sulphonic acid 5-(2-chloro-5- methoxy-phenoxy)-6-(2-hydroxy-ethoxy)-pyrimidin-4-ylamide was obtained. White crystals. Mass spectrum: ££9 (M-SOy) Preparation of starting compound 0 ( 3-Methoxyphenol was converted with sulfuryl chloride to 2-chloro-5-rnethoxyphenol according to M.Julia and Ide Rosnay, chimie therapeutic, 5, (1969), 334b VA,Y grams of ?2-chloro-5-methoxyphenol were dissolved in 0,000 ml of dry methyl ethanol and then added “, 9 gram of sodium methoxide (MeONa), followed by the addition of YO, gram of chai, YO, dimethyl chloromalonate, and the reaction mixture was stirred at a temperature of 00 C for two hours. After the solvent was distilled, the precipitate was partitioned between Toluene 1010808 and water in Separation funnel and washing.After crystallization in ethanol, (2-chloro-5-methoxy)phenoxy- dimethylmalonate white crystals with a melting point: VATA Y. c) VEY melt gram of sodium in 71 mL of methanol, after which 5.8 grams of -17-(chloro-5-methoxy)phenoxy-dimethylmalonate was added; (2-chloro-5 -methoxy)phenoxy-dimethylmalonate and 7.75 grams of formamidine acetate, and the reaction mixture was stirred by reflux for a deb and a half. and then; the solvent was distilled; Then the precipitate was taken into the water; The aqueous phase, Yo | was extracted by ethyl acetate, then the organic phase and the acid of the aqueous phase were eluted to a pH value; By cacetic acid, the compound 5-(2-chloro-5-oe) was separated.

—Yo-. 718 = m/e as a white powder. Mass spectrum: methoxy) phenoxy-4,6-(SH, 1H)pyrimidinedione .(M) 5-(2-chloro-5-methoxy) phenoxy-4,6(1 H,5H)-(— g ¥,V0 A mixture of (a pyrimidinedione) was stirred in ml of VY,0 (N-ethyldiisopropylamine) with 4 grams of <7-ethyldiisopropylamine an hour. After distillation of the volatile components VA by reflux for a period of dioxan 01 ml dioxane in POC, the precipitate was fractionated between ethyl acetate and water and washed until neutralization.After the solvent was distilled, the compound 4,6-Dichloro-5- was pure on silica gel with dichloromethane as an eluting solvent. Obtaining, after crystallization, PARANA as white crystals with a melting point of (2-chloro-5-methoxy-phenoxy)-pyrimidine from ethanol.

e) Approximately 0000 mL of ammonia at temperature = 0VA was added to a solution of 9.9 grams of 4,6-dichloro-5-(2-chloro-5-methoxy-phenoxy)-pyrimidine e.g. 1 e) in 00 mL of ethanol and thereafter; The reaction mixture was stirred at a temperature of -/7”C for 11 hours, then at room temperature for 0 © hours and finally evaporated. The precipitate was partitioned between ethyl acetate and water, then work was done

6-chloro-5-(2-chloro-5-methoxy-) on the organic phase. Then 8.57 grams of Vo .00 YAo were obtained as yellow crystals. Mass spectrum phenoxy)-pyrimidin-4- ylamine

F) 4.57 grams of the previously obtained compound was added to a solution of AY, a gram of sodium in 100 ml of ethylene glycol at a temperature of 00 C. The solution was heated to a temperature of 1100 C. for 10 hours, after which a half-saturated solution of

2-[6-amino-5-(2- grams of ? AY ammonium chloride and dichloromethane. 0 was obtained as a white solid” to which chloro-5-methoxy-phenoxy)-4 was added. pyrimidin-4-yloxy]-1-ethanol (g) in AY) silylated without any further purification. For this purpose; The aforementioned substance (Led) gram of di-AYO was dissolved and then treated with (16 chloride | ml of methylene chloride 00.15 grams at room temperature by means of Tal dimethylaminopyridine methyl aminopyridine

Yo of 1-butyldimethylchlorosilane p(0H1-005101016071011005:1). The reaction solution was stirred at room temperature for ½ hours; the solution was then filtered and concentrated; the resulting molecule was divided between

171- A half-saturated solution of ammonium chloride and ethyl acetate, then the organic phase was worked on. The crystallization of 6-[2-(tert-butyl-dimethyl-) from methylene chloride / hexane resulted in obtaining 7 grams of silanyloxy)-ethoxy]-5-(2-chloro-5-methoxy-phenoxy) -pyrimidin-4-ylamine (M-CHy) £1 + Mass Spectrum:

YA Example 8

Co in a similar way to what was mentioned in the example ?; But using 5-tert-butyl-thiophene-2-sulphonic acid 5-(2-chloro-5-methoxy-phenoxy)-6-(2-hydroxy- ethoxy)-pyrimidin-4-ylamide: pyridylearboxylic acid azide and ?- pyridyl carboxylic acid azide pyridine-2-ylcarbamic acide 2-[6-tert butyl-thiophene-2-ylsulphonylamino)-5-(2-chloro-5- 01 methoxy)pyrimidine-4- yloxy]ethy! ester (MAH) 1 4, ABS as white crystals. spectrum

V4 Example and; 2-[6-(5-tert-butyl-thiophen-2-ylsulphonylamino)-5-(2-chloro-5-methoxy-phenoxy)-pyrimidin-4-yloxy]-ethyl ester

J(M+H) 17 4,7 as white crystals. Mass spectrum:

Ye eg 6-[2-(tert-butyl-dimethyl-silanoxy)-ethoxy]-5- and using VV in the same way as in 0

S-tert-butyl- as a reaction component; It was obtained (2-methoxy-phenoxy)-pyrimidin-4-ylamine thiophene-2-sulphonic acid ~~ 6-(2-hydroxy-ethoxy)-5-(2-rnethoxy-phenoxy)-pyrimidin-4- As a white solid. Mass spectrum: 5974 0 M ylamide A: YY Example Milligram of the compound produced from the previous step To a sodium glycolate solution of 1831 Yo ml of diode 1 mg of sodium was added Add £7 ethylene glycol 5 mL of ethylene glycol

-YV- | methyl sulfoxide DMSO to complete dissolution. Leave the mixture to react at a temperature of 2290 for a period of ? hours. After cooling to room temperature, the reaction medium lost a pH value; By an aqueous solution of citric acid, then the compound formed was then extracted by means of ethyl acetate. After distillation of ethyl acetate, the compound N-[5-(2-chloro-5-methoxy- phenoxy)-6-(2-hydroxy-ethoxy)-pyrimidin-4-yl]}-5 crystallized. -isopropyl-pyridine-2-sulphonamide 2, and 175 mg of white crystals were obtained, which dissolved when the VA preparation of the starting compound reacted with 006 mg of YY + 4 6-dichloro-5-(2- chloro-5-methoxy-phenoxy)-pyrimidine mg of S-isopropyl-2-pyridine-sulphonamide and a reaction of 081 mg of 0-potassium Ktertbutylate dissolved in ? ml of dimethyl sulfoxide at 8 °C for hours. After cooling to room temperature, (als) the reaction medium was lost with an aqueous solution of citric acid; then the compound was extracted by ethyl acetate, and after the solvent was distilled, it was crystallized from ethanol. Yor mg was obtained from N-[6-chloro -5-(2-chloro-5-methoxy-phenoxy)- pydmidin-4-yl}-5-isopropyl-pyridine-sulphonamide 0 as white blouses with melting point VE = ml then: : Example YY Dissolve 1001 mg of N-[5-(2-chloro-5-methoxy-phenoxy)-6-(2-hydroxy-ethoxy)- pyrimidin-4-yl]-5-isopropyl-pyridine-2 -10 sulphonamide Ys and YA mg of 7-pyridine carboxylic acid azide in 1 ml of dry dioxane. The solution was pulverized at a temperature of 90 (90) for two hours, where the nitrogen (nitrogen) was released and after distillation of the solvent the compound crystallized 111 mg of pyridin-2-yl-carbamic acid 2-[5-15 (2-chloro-5-methoxy-phenoxy)-6-(5-isopropyl-pyridin-2-) was obtained. ylsulphonylamino)-pyrimidin-d-yloxy] -ethyl ester [Yo] as white crystals [lead] 14-141 C. Example YY oe

The compound 5-lsopropyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(3-methoxy-phenyi)-pyrimiciin-4-yij- was then prepared. pyridine-2-suiphonamide melting point: 45-174 01 C (cr) ethanol); In a manner similar to that in Example YY, the preparation of the starting compound H. 50,860 mg of N-[6-chloro-5-(2-methoxy-phenoxy)-2-(3-methoxy- phenyl)- was obtained. pyrimidin-4-yl]-5-isopropyl-pyridine-2-sulphonamide of 10? milligrams of ,6-dichloro-2-(3-methoxy-phenyl)-5-(2-methoxy-phenoxy)- pyrimidine and 471 mg of (5-isopropyl-pyridine-2-sulphonamide) K in a manner similar to that of Example YY in the second section. Ye is an example of Yi in a similar way to that of the YY example using 111 mg of 5-isopropyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy- phenoxy)-2-(3-methoxy-phenyl)-pyrimidin-4-yl]-pyridine-2- sulphonamide 3.5 mg of 7-pyridylcarboxylic acid, 1171 mg was obtained from pyridin-2-yl-carbamic acid 2-[6-(5-isopropyl-pyridin-2-ylsulphonylamino)-5-(2-.methoxy-phenoxy)-2-(3-methoxy-phenyl)-pyrimidin- 4-yloxy]-ethyl ester 0 Melting point: TeV 0A 22 (from ethanol). Example Yo a) N-[6-Chloro-5-(2-methoxy-phenoxy)-2-(Smethylsulphanyl-pyrimidin- 4-yl}-5-isopropyl-pyridine-2- was obtained sulphonamide of 4,6-dichloro-2-methylsulphanyl-5-(2-methox- 5-isopropyl-pyridine-2-sulphonamide) Ky y-phenoxy)-pyrimidine | 0 in a manner similar to that of the example .71 Melting point: 221A (from ethanol).

b) conversion of the compound by sodium glycolate to 5-isopropyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-methylsulphanyl-pyrimidin- 4-yl]-pyridine -2-sulphonamide:

Yo and the melting point: 76/A9-//*C (from ethanol). Example 176 oe

011 mg was obtained from pyridin-2-ylcarbamic acid 2-[6-(5-isopropyi-pyridin-2-yisuiphonylamino)-5-(2-methoxy- phenoxy)-2-methylsulphanyl-pyrimidin- 4-yloxy]-ethyl ester from 100 mg of 5-isopropyl-N-[6-(2-hydroxy-m ethoxy)-5-(2-methoxy-phenoxy)-2- methylsulphanyl-pyrimidin -4-yl]-pyridine-2-sulphonamide© and 2-pyridyl-carboxylic acid azide in a manner similar to what was mentioned in the example YY Melting point: 4-717 11 °C (from ethanol as an example YY (i) obtained N-[6-Chloro-2(1,3-benzodioxol-5-y1)-5-(2-methoxy-phenoxy)-pyrimidin-4-ylj-5- isopropyl-pyridine-2- sulphonamide of 4,6-dichloro-2-(1,3-benzodioxol-5-yl)-5-(2-methoxy-phenoxy)-pyrimidine |0 and (5 -isopropyl-pyridine-2-sulphonamide) K This compound was converted by sodium glycolate to N-[2-(1,3-benzodioxol-5-y1)-6-(2-hydroxy-ethoxy)-5- (2-methoxy-phenoxy)-25 pyrimidin-4-yl]-5-isopropyl-pyridine-2-sulphonamide Melting point: 840"C (from ethanol). Example YA 1 obtained 011 milligrams of pyridin-2-ylearbamic acid 2-[2-(1,3-benzodioxol-5- y1)-6-(5-isopropyl-pyridin-2-yl sulphonylamino)-5-(2- metnoxy-phenoxy)-pyrimidin-4-yloxy]- ester of 111 mg of N-[2-(1,3-benzodioxol-5-yl)-6-(2-hydroxy-ethoxy) -5-(2- methoxy-phenoxy)-pyrimidin-4-yl]-3-isopropyl-pyridine-2-sulphonamide and YoY pyridyl-carboxylic acid 2-35 in a manner similar to that mentioned In the example YY 0 degree - melting point: 4 "C (from ethanol). Example Ya (I) obtained N-[6-Chloro-5-(2-chloro-5-methoxy-phenoxy)-2-morpholin-4-yl- 4,6-dichloro-2-morpholin -4-yl- (}—-= pyrimidin-4-yl]-5-isopropyl-pyridin-2-sulphonamide ‎(5-isopropyl-pyridine-2-sulphonamide) K_pyrimidine Yo b Reaction of this compound with Sodium glycolate gave 0 We

. age no

N-[5-(2,10 chloro-5-methoxy-phenoxy)-6-(2-hydroxy-ethoxy)-2-morpholin-4-yl-pyrimidin-4- yi]}-5-isopropyl-pyridine- 2-sulphonamide Melting point: 223A (from ethanol). Example ve ) 111 mg of N-[5-(2-chloro-5-methoxy-phenoxy)-6-(2-hydroxy-ethoxy)-2- morpholin-4-yl -pyrimidin-4-yl}-5-isopropyl-pyridiae-2-sulphonamide by 0 2-pyridyl-carboxylic acid azide intopyridin-2-ylcarbamic acid 2-[5-(2-chloro-5-methoxy- phenoxy)-6-(5-isopropyl-pyridin-2-ylsulphonylamino)-2-morpholin-4-ylpyrimidin-4-yloxy]- ethyl ester Yo in a manner similar to that of the YY example using ethanol; 0116 milligrams of white crystals were obtained which decomposed at a temperature of 46 then. Example 1 5-Methyl-pyridine-2-sulphonic acid is obtained 6-(2-hydroxy-ethoxy)-5-(2- ‎methoxy-phenoxy)-2,2'-bipyrimidin-4- ylamide Melting point: 91 0'C (from ethanol) of 5-methyl-pyridine-2-sulphonic acid [6-chloro-5-(2-methoxy-phenoxy)-2,2'-bipyrimidin- 4-yl]- Yo amide and sodium glycolate Na glycolate in a manner similar to what was mentioned in Example 71. Preparation of the starting compound: 2-Amino-5-methylpyridine (I) diazotized metabolite converted to 2-bromo-5-methylpyridine Yo according to the method of JACS) F.H.Case vol (((V4£7) TA page (Yovi B) reaction of 0.8; grams of this compound in 560 ml propylene propylene glycol with, not a gram of sodium hydrogen sulfide at a temperature of 6 819 C. After cooling (J) room temperature, ½ ml of acetic acid was added drop by drop to the reaction mixture; The compound = mercapto = 0 = methylpyridine was separated, 2-mercapto-5-methyl pyridine _ formed as a yellow powder.

1hg 0*0 mL of a molar VY solution of sodium hypochlorite was added drop by drop over a period of Ve min to a two-phase mixture of 460 mL of dichloromethane of Yo mL of aqueous solution 777 of hydrochloric acid and “g of = mercapto-*-methylpyridine-2-mercapto-5-methylpyridine cooled to -10” M. and then; The organic phase was extracted 1 time © with water. The compound 0 = methylpyridine sulphochloride was obtained as a yellowish liquid after distillation of the solvent. d) The reaction of a sulphochloride with 7706 ammonium hydroxide gave 0--methylpyridine- "- sulfonamide .methylpyridine-2-sulphonamide e) 01.7 grams of 4,6-dichloro-5-( 2-methoxy-phenoxy)-2,2'-bipyrimidine 01.90 mg of ©-methylpyridine-7-sulfonamide 5-methylpyridine-2-sulphonamide and 101 mg of tert-butylated potassium butylate dissolved in 1 ml of dimethyl sulfoxide at a temperature of 80 °C for 8 hours, and after the conventional work of the reaction mixture, 401 mg of 5-methyl-pyridine-2-sulphonic acid [6-chloro- 5-(2-methoxy-phenoxy)-2, 2'-bipyrimidin-4- yl}-amide Yo Example FY In the same way as example YY From 0 V0 mg of © 5-methyl-pyridine-2-sulphonic acid = 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2, 2'- bipyridmin~4-ylamide Yo. | and Yo milligrams of 2-pyridyl-carboxylic acid azide, 001 milligrams of pyridin-2-ylcarbamic acid 2-[5-(2-methoxy-phenoxy) -6-(5-methyl-) was obtained. pyridin-2-ylsulphonyl- ‎amino)-2, 2'-bipyridimin-4-yloxy]-ethyl ester as beige crystals. Melting point: 22V AA with decomposition. Example YY − Yo a) in a manner similar to that of Example 77; From 711 mg of; 4,6-dichloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-; pyrimidine

the name _

and (5-methyl-pyridine-2-sulphonamide) K, .208 mg of 5-metliyl-pyridine-2-sulphonic acid 6-chloro-5-(2-methoxy-phenoxy)-2 was obtained. -morphoiin-4-yi-pyri-midin-4-ylamide

b) Reacting this compound with sodium glycolate gave 5-methyl-pyridine-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-morpho-© lin-4 -yl-pyrimidin-4-ylamide Melting point: 81-140 p21 (from ethanol). Example ve obtained 1117 milligrams of pyridin-2-yl-carbamic acid 2-[5-(2-methoxy-phenoxy)- 6-(5-methyl-pyridin-2-ylsulphonylamino) Veo -2-morpholin-4-yl-pyrimidin-4-yloxy]-ethyl ester 0 mg of © 5-methyl-pyridine-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5- (2- methoxy-phenoxy)-2-1 morpholin-4-yl-pyrimidin-4-ylamide and 2-pyridyl-carboxylic acid hy azide ,43 same as in example YY degree loath 75110”m with decomposition. Example Yo Yo Yo treated 110 mg of 5-methyl-pyridine-2-sulphonic acid 6-(2-hydroxy-ethoxy)- 5-(2-methoxy-phenoxy)-2-morp - holin-4-yl-pyrimidin-4-ylamide in !I hope dichloromethane is safe by ? mL of a 1.1 M solution of phosgene in toluene 6″Pr201. After an hour at room temperature, it was found that the chloroformate (SS) was completely dissolved. After that, the excess amount of the reagent was distilled; the precipitate was taken in a mixture of chloroform 0 and pyridine, after which 1 was added # grams of =F (hydroxymethyl furan (J ssi (hydroxymethyl)), then the mixture was left to react at a temperature of 100 "C for a period of ? hours. After the traditional work, the compound was added to silica gel (dichloromethane - dichloromethane) 1 : 4 diethyl ether by volume as eluting mixture) © milligram was obtained from carboxylic acid furan-3-ylmethyl ester 2-[5-(2-methoxy-phenoxy)-6-(5-methyl-pyridin- 2-sul-phonylamino)-2-morpholin-4-yl-pyrimidin-4-yloxy]-, ethyl ester Yo Mass spectrum: 48.5 J(M-H)-] z | 41 yr Example +? 4-[4-chloro-5-{2-chioro-3-methoxy-phenoxy )-6-methyl- 1.1 g of : 5-isopropyl-pyridine-2-sulphonamide © gram aged YV,A and pyrimidin-2-yl]-morpholine under 22 Ye) dry dimethyl sulphoxide mL of dimethyl sulfoxide 1101 in potassium h. After that; a binary distillation was done methyl sulfoxide; Then the precipitate was partitioned between 11 for argon ©

Cl of hydrochloric acid, then the organic phase was washed to neutralize 1 ethyl acetate and a solution of 0’ solvent and the precipitate was recrystallized from ethanol. After that, G35 organic phase was obtained; Then 5-isopropyl-pyridine-2-sulphonic acid 5-(2-chloro-5-methoxy-phenoxy)-6-methyl- grams of 2rmorph-olin-4-yl-pyrimidin-4-ylamide ov E= M mass spectrum: Ye

YY Example A gram of dioxide 7.1 grams of the compound obtained in Examples 7 and 1 was stirred at an autoclave in an autoclave in 560 ml of selenium dioxide silicon hours. Then the reaction mixture was filtered and the filtrate was concentrated. 1 temperature 1710"C for organic matter; then the solvent was evaporated and the precipitate was purified over shall ethyl and water. COA was dried. The precipitate was fractionated between V0 5-isopropyl-pyridine-2- grams of 1, 57 Silicagel with ethyl acetate/hexane was obtained sulphonic acid 5-(2-chloro-5-methoxy-phenoxy)-6-formyl-2-morph-olin-4-yl-pyrimidin-4- ylamide

VA melting point:

YA example 7 in ¥ ml of ethanol TV g of the compound obtained in Example 1.1 The reaction mixture was stirred and treated with 1.014 g of sodium borohydride. ethanol, then the precipitate was fractionated between 1 hour ethanol. and then; The ad ethanol was distilled at a temperature of 80 °C from the organic phase ⩾N of hydrochloric acid and a solution of chloroform chloroform _ with water, then dried; The solvent was evaporated and the precipitate was separated by chromatography on silica gel using 0.177 Yo chloroform-methanol. After recrystallization from dichloromethane-ethanol, it was obtained

© grams of 5-isopropyl-pyridine-2-sulphonic acid 5-(2-chloro-5-methoxy-phenoxy)-6- hydroxymethyl-2-mor,pholin-4-yl-pyrimidin-4-ylamide As fusion pV vo example va ° 17 g of the compound obtained in example YA was stirred in 7.8 mL of POCly with AT 0, + g of PCls at 10°C for two hours. and then; Was distilled and 7001 and then 552} the precipitate between ethyl acetate and a solution (Sle) of sodium bicarbonate. The organic phase was washed with water, then Gilt and the solvent was evaporated. The precipitate was separated by chromatographed over silica gel using chloroform cmethanol 0 and then recrystallized from dichloromethane — ethanol “ethanol” obtained +0 ,V + gram of 5-isopropyl-pyridine-2-sulphonic acid 5-(2- 4 chloro-5- ‎methoxy-phenoxy)-6-chloromethyl-2 -morpholin-4-yl-pyrimidin-4-ylamide Veo degree: leary Example 560 Yo add 1 ,171 grams of the compound obtained in Example 99 into a sodium glycolate solution of YO, + a gram of ethylene glycol and 1071 grams of sodium ©800:0.The reaction mixture was stirred At a temperature of 80°C under argon for two hours.After that, ethylene glycol was distilled, then the precipitate was divided between ethyl acetate and a solution of 1N of hydrochloric acid.The organic phase was washed with water, then dried on sodium sulfate sodium sulphate 0 and the solvent was distilled off. The precipitate was recrystallized from an ether - a petroleum ether. Then obtain 6.014 grams of 2-6 5-(2-chloro-5-methoxy-phenoxy)-6-(2-hydroxy-ethoxymethyl)- morpholin-4-yl-pyrimi- din- 4-ylamide da fusion: 11 1 km. Example 51 Yo obtained Pyridin-2-ylcarbamic acid 2-[5-(2-chloro-5-methoxy-ephenoxy)-6 -(5-isopropyl-pyridine-2-sulphonylamino)-2-morpholin-4-yl-pyrimidin-yl-methoxy]-ethyl ester

© Mass spectrum: 711 = (M-H) in the same way as in the example? of the compound obtained in Example 50. Example 47: Pyridin-2-ylcarbamic acid 5-(2-chloro-5-methoxy-phenoxy)-6-(5-isopropyl-pyridin-2-ylsulphonylamino)-2-morpholin-4-yl is obtained -pyriinidin-4-ylinethyl ester© Mass Spectrum: (MAH) = 1695 In a manner similar to that in Example ¥ of the compound obtained in Example FA Example 47 5-lsopropyl-pyridine- was obtained 2-sulphonic acid (RS)-5-(2-chloro-5-methoxy- phenoxy)-6-(2,2-dimethyl-1,3-dioxolan-3-15 ylmethoxymethyl)-2-morpholin-4 -yl-pyrimidin- 01 4-ylamide mass spectrum: 04-11- VV in a manner similar to that in Example 40 of the compound obtained in Je 5” and (T= RS) 7-dioxolan-=F=a-dioxolan-;-methanol sodium (RS)-2,2-dimethyl-1,3-dioxolan-4-methanol Na Example 64 yo A solution of 0 was treated .06 g of compound prepared in example EY in “mL dioxan by” mL of 1 M HCl 1101 and heated to PAL for 11 minutes. After evaporation, the precipitate was separated by chromatography on silicagel using chloroform-methanol, and 5-isopropyl-pyridine-2-sulphonic acid (RS)-5-(2-chloro-5-methoxy-phenoxy)6-(2,3-) was obtained. dihydro- (xy -propoxymethyl)-2-morpholin-4-yl-pyrimidin-4-ylamide Ye. Melting point: 111 * M; mass spectrum: SAYY = (M-H) example M solute 50 mg sodium In 0 © ml of ethylene glycol released at a temperature of 5% the solution was cooled somewhat and then 1.96 grams of 5-isopropyl-pyridine-2-sulphonic acid 6-chloro-5-(2-) was added methoxy-phenoxy)-2-morpholin-4-yI-Yo pyrimidin-4-ylamide

The resulting solution was stirred at 0050°C for YE 1 hour; Then the solvent was removed under high vacuum and the precipitate was dissolved in 50 mL of water. foamy hours at #*C; foe As ALE ale 5 8) Day Cat celal a do £0 bl ile A cil Lal was filtered by stirring with 1 N aqueous solution of hydrochloric acid until the pH decreased to ©,©. The aqueous phase was extracted several times with ethyl acetate, then the organic phases were washed twice with water and once with a saturated solution of sodium chloride. The organic phases that were unified were dried and then concentrated until crystallization was complete (about ¾ ml). The crystals were vacuum filtered, washed with ether, and dried. 1,044 grams (770) of white crystals were obtained from 5-1sopropyl-pyridine-2-sulphonic acid so 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2 - morpholin-4-yl-pyrimidin-4-ylamide Yo Melting point: 571-600" C. Mass spectrum: =(M-H)- 88.8 Preparation of starting compound Z A solution of 0, 18 grams of 4,6-dichloro-5-(2-methoxy- phenoxy)-2-morpholin-4- ylpyrimidine and 7.17 grams (AAA) mmol) of ©-isopropyl-pyridine-7 - Sulfonamide 10 potassium salt 5-isopropyl-pyridine-2-sulphonamide potassium salt in Yo ml of Di-Je sulfoxide dry to a temperature of 80 C for 1 hour Ja Disappearance of ALAN chloride Dichloride was completely dimethyl sulfoxide was removed under high vacuum up to vacuum, then precipitated in 380 Ve ml of water and the aqueous solution was washed three times with diethyl ether. Thereafter acidified the solution to a pH value*, by means of 1N of hydrochloric acid then the product 0 was extracted three times with ethyl acetate The organic phases were washed three times with water and finally with a saturated solution of NaCl 001T056; Then they were frozen, dried with sodium sulphate, and evaporated. The crystalline precipitate was digested twice by Jal absolute diethyl ether to remove traces of .5-isopropyl-pyridine-2-sulphonamide, and the remaining crystals were filtered and then dried. 1.16 grams (£371) was obtained from S-isopropyl- pyridine-2-sulphonic acid 6-chloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin- 4-0 ylamide as white crystals, melting point: VI = TA (22) mass spectrum VAY = (M-H)-

Mother Example 576 obtained ‎5-tert.Butylthiophene-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2- ‎methoxy-phenoxy-2-morpholin-4-yl-pyrimidin-4- ylamide as a white solid with a yield of 54 mass spectrum 070.0 +04711; in a manner similar to example 0£ after a reaction period of 01 hours at 1010°C with the addition of dimethyl sulfoxide as a dissolving compound (dimethyl ethylene glycol Sulfoxide ©: ?). morpholin-4-yl-pyrimidin-4-ylamide 01 as white crystals with a yield of 747 in a manner similar to that in example £0 after a reaction period of 22 hours at a temperature of 660 22 : mass spectrum: (M-H)- oYo,Y example 548 i Vo obtained the compound 3,5-Dimethylisoxazole-4-sulphonic acid 6-(2-hydroxy-ethoxy)- 5(2-methoxy-phenoxy)-2-morpholin-4-yl -pyrimidin-4-ylamide as white crystals with a melting point of 4-47" C. Mass spectrum: 570.4 (M-H) in a manner similar to example 0 after a reaction time of ¥ ½ hours at 560 pV example 494 0.0 mg of sodium was dissolved in 0.¥ ml of ethylene glycol at a temperature of 0 0” C. The solution was left to cool to room temperature, then 760 mg of 2,5-dichlorothiophene was added -3-sulphonic acid 6-chloro-5-(2-methoxy-phenoxy)-2,2'-bipyrimidin-4- aay ylamide Heating to a temperature of 00°C for two hours, the glycol was removed under a high vacuum, then the precipitate was dissolved solid in 10 ml water. The product was precipitated by adding 17 ml of acetic acid. and after yo filtering; And washing with water and drying at 0 "m under a vacuum Je, it was obtained YAY mg

i secret wv) 0 of pale beige crystals of 2,5-dichlorothiophenc-3-sulphonic acid 6-(2-hydroxy- ethoxy)-3-(2-35 methoxy-phenoxy)-2 ,2"-bipyrimidin-4-ylamide Melting point: 0-157 60°C Mass spectrum: (074) K470 (MSOC) Preparation of starting compound A solution of 0.744 g of 4,6-dichloro- 5-(2-methoxy-phenoxy)-2,2'- bipyrimidine and + 0 €,+ g of 2.5-dichlorothiophene-3-sulphonamide potassium salt in ¾ mL of dry dimethyl sulfoxide at room temperature 11 sad hours After that, 117 grams of tripotassium butylate was added, and the reaction was completed within a period of ½ hours.The reaction mixture was poured on ml of ice water and extracted by 40 ml of diethyl ether, by 0 removal Excess amount of starting compounds From the aqueous phase by removing the salt with a saturated solution of sodium chloride (Ja Yo), 2,5-dichlorothiophene-3-sulphonic acid 6-chloro- 5-(2-methoxy) was obtained. -phenoxy)-2,2'-bipyrimidin-4-ylamide [which was separated] by filtration and washing with ether (10+ grams for beige powder). sodium in water and the suspension was acidified by acetic acid and extracted by ethyl acetate to which a small amount of dichloromethane was added. The organic phase was washed twice with a saturated sodium chloride solution, then dried with magnesium sulfate, 1850/2, and evaporated under reduced pressure. The precipitate was finely ground by diethyl ether and hexane and then dried. 1,900 grams (7254) of beige Yo powder with a melting point of: E+ 22 (with decomposition) mass spec 744 (04-502+0) were obtained in a similar manner, using -5 dimethylisoxazolyl-4-sulphonamide potassium 3 3,5-dimethylisoxazole-4-sulphonic acid 6-chloro-5-(2-methoxy-phenoxy)-2,2"- bipyrimidin-4-ylamide BYR 771 as a reddish-beige powder, melting point: 184-1817, then Yo mass spectrum; K = (M(SO,+OCH)) FAY (£AA - ex. 0 ve

3,5-Dimethyl-isoxazole-4-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2- methoxy-phenoxy)-2,2'-bipyrimidin-4-ylamide was obtained. As a beige powder with a melting point of 10M 701-4 Mass spectrum: 814 (M+)£00 (50 + 247) – 414 (05;-0.yt©); In a manner similar to Example 49. Example oy 5 A solution of AAA mg of pyridine-?"-carbonyl pyridine-2-carbonyl 15 azide of absolute dioxane was kept at temp PAs for 10 The solution was left to cool with a kind of water, then 004 grams of the compound that had been prepared in the example £0 was added, then the temperature of the solution was set to 48 °C for a period of hours, after that it was evaporated to dryness aly the precipitate in ethyl acetate; then washed twice with water and once with a saturated solution of sodium chloride; the organic phases were collected; then dried and concentrated; the crystals of the product were separated and for purification; the separation was carried out by chromatography on silica gel using ethyl acetate / di chloromethane (1:1) and 971 milligrams (710) of white crystals were obtained from -5(-6[-2 pyridin-2-ylcarbamic acid isopropyl-pyridin-2-ylsulphonylamino)-5 -(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidm- 4-yloxylethyl ester 7-701 lead 1007*m mass spectrum 74.4 (M-H) infrared spectrum 1 red 17710 (KBr) centimeter ' (carbamate). Example oY obtained Pyridin-2-ylcarbamic acid 2-[6-( 2,5-dichlorothiophen-3-ylsulphonylamino)-5- (2-methoxy- phenoxy)-2, 2'-bipyrimidin-4-yloxy]ethyl ester 0 as white crystals, melting point 997-1940*m; mass spectrum 395.1 (((MHH)T) The infrared spectrum of 1777 (KBr) centimeters' (carbamate) has a yield of 7761 in a manner similar to that of Example 51 of the compound prepared in Example 44 . oy example : Pyridin-2-ylcarbamic acid 2-[5-(2-methoxy-phenoxy)-6-(3, 5-dimethyl- isoxazol-4-ylsulp- honylamino)-2 is obtained. 2'-0 bipyrimidin-4-yloxyJethyl ester 5 as yellow crystals al 4 Color Melting Point: LOY VA=Y VY Mass Spectrum: 178 “, (MH) IR Spec Vo

(potassium bromide): 1777 cc' (carbamate) with a yield of 7718 in a manner similar to that mentioned in Example 0) from the compound prepared in Example 0 5. Example of A The compound Pyridin-2-ylcarbamic was obtained acid 2-[6-(5-tert-butylthiophen-2- ylsulphonylamino)-5-(2-niethoxy-phenoxy)-2-morpnolin-4-yl-pyrimidin-4-yloxy]-ethyl ester © as material white foamy; Mass spectrum: 187.5 (MAH)- with a yield of 7950 By the same method as in example ©1 from the compound prepared in example AN example co Pyridin-2-ylcarbamic acid was obtained 2-[6-(2, S-dichloro-thiophen-3- ylsulphonylamino)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yloxy}-ethylester | 0 white crystals with a melting point of 976-1940*C; mass spectrum: 10.7 (M-HY with a yield of 7855 in the same manner as in Example 0) of the compound prepared in Example 47. Example 570 The compound Pyridin-2-ylcarbamic acid 2-[6-(3, 5-dimethyl-isoxazol-4- ylsulphonylamino)-5-(2-methoxy-phenoxy)-2-morpholin-4- was obtained. yl-pyrimidin-4-yloxy]-ethylester 8 as white crystals with a melting point of 1-017 10*m mass spectrum: 140.4 (M-HY with a yield of 7760 in the same way as in Example 0) of the compound which Prepared in Example 448. Example ov dissolve 5-1sopropyl-pyridine-2-sulphonic acid 6-(2-hydroxy- ethoxy)-5-(2-methoxy- phenoxy)-2-morpholin-4-yl-pyrimidin-4 -ylamide | 0 (0,£© milligram) in N,N-dimethylacetamide (© mL). 14.4 mg of a 7700 suspension of sodium hydride at room temperature was added and the mixture was infused for 0? minute. Finally add “- chloropyrimidine 2-chloropyrimidine (/A 111 mg). The reaction mixture was stirred for VA 1 hour at room temperature and then poured into ice water. A saturated solution of 107.01 ammonium chloride was added and the mixture was extracted by acetate The organic phase, YO, was washed with water, then dried on magnesium sulfate SEs, and the precipitate was separated by chromatography on silicagel using methylene chloride/methanol (1/001) as an eluting mixture.

-?1- ‎ : 5-isopropyl-pyridine-2-sulphonic acid {5-(2-methoxy-phenoxy)-2- morpholin-4-yl-6-[2- (pyrimidin-2-yloxy)-ethoxy] -pyrimidin-4-yi}-amide

As white crystals. The mass spectrum of 174 (MH) h oA Jia (a) in a similar manner as in Example 0 and with the reaction - 5-isopropyl-pyridine-2-sulphonic acid [6-chloro-2-(3-methoxy-benzyi) )- 35-(2-m ethoxy- phenoxy)-pyrimidin-4-yl]-amide: With sodium in ethylene glycol, the compound 5-isopropyl-pyridine-2-sulphonic acid was obtained. [6-(2-hydroxy-ethoxy)-2-(3-methoxy-benzyl)-5-(2- Yo ‎methoxy-phenoxy)-pyrimidin-4-yl}-amide as a white foaming agent mass spectrum 579 7, (M-H) Preparation of starting compound (b) 0 g of =F methoxyphenylacetonitrile was dissolved in Vo ethanol (Ja 001) ethanol and the solution was saturated with hydrogen chloride hydrogen chlorid at room temperature.The mixture was then stirred for a period of VY hours at room temperature.The solution was cooled to 0°C and the precipitated crystals were suctioned.The crude product was recrystallized from acetone/diethyl ether.It was obtained On 2-(3-methoxy-phenyl)-acetimidic acid ethyl ester hydrochloride as a white crystalline solid, mass spectrum: CMD) YAY (z) Y. 2-(3-Methoxy-phenyl)- acetimidic acid ethyl ester hydrochloride (VY) g) in ethanol (Ja 001) and was treated at -22VO— by VE ml of liquid ammonia. The mixture was left at room temperature for a period of ½ hours and then evaporated at a rotary evaporator. The precipitate was suspended in acetone, then the precipitated crystals were suctioned out and dried under high vacuum, after which 2-(3-methoxy-phenyl)-acetamidine hydrochloride Yo was obtained as a white crystalline solid. Mass spectrum: (M) 11664 Wo

(d) Sodium YY (g) was added in methanol (+mL) and 2-(3-methoxy-phenyl)-Yo ) acetamidine hydrochloride #) and (2-methoxyphenoxy)-malonic acid dimethyl ester were added VYSTY) in grams) respectively at room temperature. the mixture séd© hours at room temperature; Then it was concentrated in a rotary evaporator and the crude product was added to the water. The organic phase was washed with ethyl acetate; J was set to a pH of 1 and the precipitated crystals were aspirated and then dried under a Jey vacuum. dle, 2-(3-methoxy-benzyl)-5-(2-methoxy-phenoxy)- pyrimidine-4,6-diol was obtained as beige crystals. Mass spectrum: M) y of )=(2-(3-Methoxy-benzy!)-5-(2-methoxy-phenoxy)-pyrimidine-4,6-diol VE) Ve grams ) acetonitrile 501 (mL). cipal collidine (Je©,Y ¢) collidine and phosphorus oxychloride (YY,Y) mL) at room temperature and then stirred the mixture for 4 hours at room temperature. Pour the mixture into ice water and extract by ethyl acetate. washing of the organic phase with a semisaturated solution of potassium bicarbonate; Then, the magnesium sulfate was collected and evaporated. take the precipitate in hexane/diethyl ether; The filtrate was then filtered and evaporated at a rotary evaporator. Subsequently, he lost Vo and obtained 4,6-dichloro-2-(3-methoxy-benzyl)-5-(2-methoxy-phenoxy)-pyrimidine as light brown crystals. mass spectrum. (M) 2900 (f) in a manner similar to that of example £0" and by reacting 4,6-dichloro-2-(3-methoxy-benzyl)-5-(2- methoxy-phenoxy)-pyrimidine With potassium S5-isopropyl-pyridine-2-sulhonamide, 5-isopropyl-pyridine-2-sulphonic acid [6-chloro-2-(3-methoxy-benzyl)-5-(2-) was obtained. methoxy-phenoxy)-pyrimidin.-4-yl]-amide | 08 yellow foam. Mass spectrum: (M-H) 887.1 eq (1) in the same way as in the £0 example and by the reaction of 5-isopropyl-pyridine-2-sulphonic acid [6-chloro-2-. (3-methoxy-benzyl) -5-phenoxypyrimidin-35, 4-yl]-amide with sodium in YO ethylene glycol was obtained -2(-6[ 5-isopropyl-pyridine- 2-sulphonic acid (hydroxy-ethoxy)-2-(3-methoxy-benzyl)-5-pheno- xy-pyrimidin-4-yl]-amide a

Light yellow crystals. Mass spectrum: (MH) 0£3,Y Prepare cll (b) in a manner similar to that in Example 88d. And by condensing 2-(3-methoxy-phenyl)-acetamidine hydrochloride with phenoxy-malonic acid dimethyl ester, 2-(3-methoxy- benzyl)-5-phenoxypyrimidine-4, 6-diol was obtained. © Yellow foam. Mass spectrum: 4 YY 0. L” (z) in a manner similar to that of the 4-dehode example and by the chlorination of 2-(3-methoxy-benzyl)-5-phenoxypyrimidine-4,6-diol by phosphorus oxychloride, 4,6-dichloro-2-(3-methoxy-benzyl)-5-phenoxy-pyrimidine was obtained as yellow crystals. Mass spectrum: 300 (OM) Ye (d) in a manner similar to that of Example 45; And by reacting 4,6-dichloro-2-(3-methoxy-benzyl)-5- phenoxy-pyrimidine with potassium 5-isopropyl-pyridine-2-sulphonamide 28, 5-isopropyl-pyridine- was obtained. 2-sulphonic acid [6-chloro-2-(3-methoxy-benzyl)-5-phenoxy-pyrimidin- 4-yl]-amide as a yellow foam. Mass spectrum: (M-H) #07 1 Example Te 5-Isopropyl-pyridine-2-sulphonic acid [6-(2-hydroxy-ethoxy)-2-(3-methoxy- a benzyl) (-5-phenoxy-pyrimidin-4-yl]-amide (00 mg) in dry methylene chloride (¥ ml) 0 was then added boron tribromide (1 mg) in methylene chloride Y) chloride ml) at zero temperature. The mixture was stirred for two hours at a temperature of 0 * C, then 0 time; further hours at room temperature; Then, it was evaporated in a rotary evaporator, then the precipitate was separated by chromatography on silicagel using methylene chloride / ethyl acetate as an eluent mixture, and 5-isopropyl-pyridine-2-sulphonic acid [2-(3 -hydroxy-benzyl)-6-(2-) was obtained. hydroxy-ethoxy)-5-phen- oxy-pyrimidin-4-yl]-amide | as white crystals Mass spectrum 0 J(M-H) 875,1 Yo Example: Tablets can be prepared It contains the following ingredients in traditional style: Wo

Add the compound of the formula 1,0010 milligrams lactose 0 milligrams lactose Lis yo corn starch milligrams that tale; Magnesium stearate 1 milligram Example B: Capsules containing the following components can be prepared in the traditional way: The compound with the formula 1 YO lactose 1801086 0 milligram Lis yo corn starch mg that talc © mg eg g gelatin 0 : gelatin mg £,Y phenol J sid mg water for injection up to 1 mL eg d © 0000 mg of the compound of formula 1 is suspended in #6 mL of 812 Myglyol and 1 gram of benzyl alcohol This suspension is filled into a container containing a dosing valve. 0.5 grams of Freon 12 is filled into the vat under pressure through the valve. Freon is dissolved in a mixture of Myglyol Benzyl Alcohol by shaking. The spray container contains about 100 single doses, which can be used separately. Yo

Claims (1)

F: Claims 1-1 Compound with the formula: 1CZ RISO;NH RY R2 7 o RS N = RY : catnha 1 where: RY ¢ is a non-ring A congener chosen from the group consisting of unsubstituted © rings of ?-furyl Q-furyl pyrimidinyl «pyrimidinyl 7-pyridyl 2-pyridyl 1 *-pyridyl 3-pyridyl € -pyridyl -4; 0 ?-diazinyl 0 1,2- diazinyl %— l-diazinyl -1,4- thienyl J—if~Y «morpholino s—il si sa -2 “-thienyl-3 cthienyl A isoxazolyl cisoxazolyl coxazolyl thiazolyl “thiazolyl q imidazolyl 1”: pyrrolil epyrrolyl benzofuranyl benzofuranyl benzothienyl cindolyl Jd sa cbenzothienyl | 0 cpurinyl thiomorpholino 11 piperidino quinolyl isoquinolyl and quinazolyl 0 or the aforementioned heterocyclic rings mono- or di-substituted by 0-alkyl Cy; alkyl alkanoyl “Cry halogen Camino sis halogen mono-alkylamino | Cy alkyl chydrogen Cy alkoxy Cy alkylthio sf alkoxy Cry 10 alkylsulphonyl B©-alkoxy alkoxy phenyl alkoxy VA ©-phenyl alkylenedioxyphenyl b and a non-4-homocyclic ring selected from the group consisting of unsubstituted rings of 2-3-furyl-furyl -1 cfuryl | 0 pyrimidinyl elastane «rum» "-pyridyl 2-pyridyl ?-pyridyl 1 ; -pyridyl 1 4-pyridyl ?- diazinyl -1,2; ,4 Alive 0 3- thienyl lenyl «2- thienyl ? Benzofuranyl cpyrrolyl imidazolyl 4 “piperidino su yu sthiomorpholino sid sé se sd ¢purinyl purinyl “indolyl indolyl Yo ring non-quinazolyl quinazolyl isoquinolyl isoquinolyl quinolyl quinolyl 1 The aforementioned congener alkyl, which is mono- or di-substituted by an alkyl YY mono- mono- alkyl amino camino amino halogen “Cy; alkanoyl YA” C7 dialkylamino or dialkyl amino C17 alkylamino ~~ Y4©, alkoxy “Cg alkyl 13 is selected from the group consisting of an alkyl Y.” C17 hydroxyalkyl 7 haloalkyl formyl (formyl Y) - T-7.011 (0) (f)-aminoalkyl amino alkyl TY from RY RY select ((CHY)m-O-(CR*R"),-Y-R' 5 (CHy)m-O -(CR'RONH, ~~ YY) and the Cry alkoxy chydrogen consisting of hydrogen depend VE halogen Yo is a heterocyclic selected from the group consisting of RY 5 . pyrimidinyl S-furyl ?-furyl 2-furyl unsubstituted groups of ?-furyl VY 1 d-pyridyl ; -pyridyl 3-pyridyl Jue 2-pyridyl lidirib-1 pyrimidinyl YA —Y morpholino sil sd y se ¢1,4- diazinyl -diazinyl «VY ¢1,2- diazinyl ?- diazinyl ¥4 «< imidazolyl imidazolyl <thiazolyl thiazolyl ¢isoxazolyl isoxazolyl ¢3- thienyl p-thyl indolyl <benzothienyl benzofuranyl ¢benzofuranyl benzofuranyl ¢pyrrolyl 1 quinolyl epiperidino piperidino cthiomorpholino sid sd ses <purinyl ¢indolyl or heterocyclic cquinazolyl and quinazolyl isoquinolyl isoquinolyl <quinolyl a .:©; mono-alkylamino camino amino <halogen ¢Cy7 alkanoyl 5” C17 alkyl substituted with a group to be chosen from Alkyl phenyl and phenyl “Crp” Jr6 or the £7 trail alkyl and alkyl halogen “Cy. alkoxy 7 1 | shell where each separately is a hudrogen or an alkyl A 4 is a ketalized 1,7-dihydroxy-ethene ketalized 1,2-dihydroxy ¢tethylene 0. 51 is selected Y of the group “-=O(CO)NH- “~0-C(0)0- - “—NHC(0)O- NH(CO)NH- oY gt PRs Y Gwin oY A equals zero or m of 1 "-compound of claim 1 wherein 82 is selected from group Y consisting of the chydrogen pyrimidinyl epirimidingl pyridyl morpholino ? .| cmorpholino thiomorpholino mc100000; Epiperidino “phenyl J— “Cy; alkoxy <benzodioxlyl benzodioxolyl epyrrolidino ¢ .Cy7 alkylthio and alkyl ir ° 1 *- the compound mentioned in claim No. 0) wherein RP is a moiety that is -0- chosen from the group consisting of 0117 pg)-0-, Y RO 5-O(CH-Y-R® (CRRNH; ¥) 3-furyl ¢ 1,4- diazinyl morpholito 1,2- diazinyl Jt 3b) 4-pyridyl ?-pyridyl 1° isoxazolyl cisoxazolyl oxazolyl coxazolyl imidazolyl dimidazolyl pyrrolid no pyrrolyl or pyridino .piperidino OCH) where 183 is the oF moiety of claim number beg;-compound 1: ~(O)(CONH- is Y and Y-R' Y - that 3c is the moiety Cus oF the compound mentioned in claim No. 0-1 0 ..)0(:0)0(0- and not an OCH) YR Y - that 8 is the compound Cua radical mentioned in claim No. 7 -1 NH(CO)NH- are Y and O(CHy)-Y-R® that 8 are selected from Cua) the compound mentioned in claim No. VY 1 formyl bert formyl alkoxy alkyl group consisting of Alkyl "CH,0- alkyl and alkyl C1.7 hydroxyalkyl 0 haloalkyl haloalkyl ft of R ® the compound mentioned in claim No., whereby A 1 is chosen Suryl and pyrazinyl pyrazinyl The group that consists of pyridyl "83 is chosen as the phrase Cus) the compound mentioned in Claim No. 4 - 1 ethoxy chydroxy for VY hydroxy From: Spall the compound mentioned in claim No. 9 whereby 0 -1 is chosen: the group consisting of Y 5-tert-butyl-thiophene-2-sulphonic acid 6-(2-hydroxy-ethoxy)- 5-(2-methoxy- Y phenoxy)-2,2'-bipyrimidin-4-ylamide, ¢ 5-tert-butyl-thiophene-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2- methoxy- 5 phenoxy)-pyrimidin-4-ylamide, 1 5-(2,2-climethyl-propionyl)-thiophene-2-sulphonic acid 6-(2-hydroxy-ethoxy)- VY 5-(2-methoxy-phenoxy )-2,2'-bipyrimidin-4-ylamide, A 5-isopropyl-pyridine-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy- q phenoxy)-2,2"- bipyrimidin-4-ylamide, 01 Woe —£4- pyridine-3-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2'- 11 bipyrimidin-4-ylamide, VY . 5-tert-butyl-thiophene-2-sulphonic acid 5-(2-chloro-5-methoxy-phenoxy)-6-(2- VY hydroxy-ethoxy)-pyrimidin-4-ylamide, \¢ 5-tert-butyl -thiophene-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy- \o phenoxy)-pyrimidin-4-ylamide, 5 N-[5-(2-chloro-5-methoxy) -phenoxy)-6-(2-hydroxy-ethoxy)-pyrimidin-4-yl]-5- VY isopropyl-pyridine-sulphonic, YA 5-isopropyl-N-[6-(2-hydroxy-ethoxy)-5- (2-methoxy-phenoxy)-2-(3-methoxy- 13 phenyl)- pyrimidin-4-yl]- pyridine-2- sulphonamide, and | 5-isopropyl-N-[6-(2- hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-methyl leaching sulphanyl- pyrimidin-4-yl]- pyridine-2- sulphonamide, YY N-[2-(1,3-benzodioxol-) 5-y1)-6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)- yy pyrimidin-4-yl]-5- isopropyl-pyridine-2- sulphonamide, Y¢ N-[5- (2-chloro-5-methoxy-phenoxy)-6-(2-hydroxy-ethoxy)2-morpholin-4-yl- Yo pyrimidin-4-yl]-5- isopropyl-pyridine -2- sulphonamide, YA 5- methyl pyridine-2- sulphonic acid 6-(2- hydroxy-ethoxy)-5-(2- methoxy- YV phenoxy)-2,2'-bipyrimidin-4-yl amide, YA 5- methyl pyridine-2- sulphonic acid 6-(2- hydroxy-ethoxy)-5-(2- methoxy- YA phenoxy)-2- morpholin -4-yl-bipyrimidin-4-yl amide, Ye 5-isopropyl-pyridine-2-sulphonic acid 6-( 2-hydroxy-ethoxy)-5-(2-methoxy- 1 phenoxy)-2- morpholin -4-yl-bipyrimidin-4-ylamide, vY 5-tert-butyl-thiophene-2-sulphonic acid 6-(2- hydroxy-ethoxy)-5-(2-methoxy- YV phenoxy)-2- morpholin -4-yl-pyrimidin-4-ylamide, nene 2,5-dichloro-thiophene-3-sulphonic acid 6-(2 -hydroxy-ethoxy)-5-(2-methoxy- Y© phenoxy)-2- morpholin -4-yl-pyrimidin-4-ylamide, 1 ARE: mm 3,5-dimethyl isoxazol-4-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy- vv phenoxy)-2- morpholin -4-yl-pyrimidin-4-ylamide, VA 2,5 -dichloro-thiophene-3-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy- 1 phenoxy)-2,2"-dipyrimidin-4-ylamide, and Ee 3,5-dimethyl isoxazol- 4-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy- 1 phenoxy)-2,2"-dipyrimidin-4-ylamide. L Whereas 18 is a 1-aminoethoxy of the compound according to Claim No. 1-1a .aminoethoxy | 1 of claim No. 10; Where the compound is Les Compound 1 - 1 5-tert-butyl-thiophene-2-sulphonic acid 6-)2- amino -ethoxy)-5-(2-methoxy- Y phenoxy)-2'-dipyrimidin-4-ylamide. 7 From the group consisting of RY the compound according to claimant 1- where 1-1 Cra JI is chosen pyridyl substituted with the group that is chosen from pyridyl oe b di-mono ben alkylamine amino Justi mono amino halogen * pyrimidinyl pyrimidinyl Cy7 alkanyl p and alkanyl di meaning alkylamino sue ; alkyl amino halogen Cry pyrimidinyl substituted with the group that is Selected from alkyl © di di alkyl amino from C17 mono-mer alkylamino camino isoxazolyl cisoxazolyl isoxazolyl Cog alkanyl Cp alkylamino 1 amieno ¢halogen Cry is substituted with an element of the alkyl group A di Cry di-alkylamino Cr; Alkanoyl alkylamino 0 monoalkyl camino sisal chalogen halogen “sind Cry” group consisting of alkyl 11 gp tel gb and alkanoyl alkylamino dialkyl amino “C17 mono flexible alkylamino amino VY Wo -1e- “Cp7 alkanyl 0 thienyl sthienyl and thienyl substituted by alkyl “Cig halogen” 1810860 V¢ amino camino mono-alkyl amino alkylamine ben “C17 mono di J amino alkylamino 0 bir di bitter and C1.7 alkanyl -04 1 compound according to claim no.; And it is chosen from the group consisting of: pyridin-2-ylcarbamic acid 2-[6-(5- tert-butyl-thiophene-2-yl-sulphonylamino)- Y 5-(2-methoxy-phenoxy)-2 ,2"-bipyrimidin-4-yloxy]-ethyl ester, Y pyridin-2-ylcarbamic acid 2-[5-(2-methoxy-phenoxy)-6-(5-pentyl-thiophene-2- ¢ yl-sulphonylamino)-2,2"-bipyrimidin-4-yloxy]-ethyl ester, © pyridine-2-ylcarbamic acid 2-[6-(5-(2,2-dimethylpropionyl-thiophene-2-yl-) 1 l sulphonylamino)-5-(2-methoxy-phenoxy)-2,2'-bipyrimidin-4-yloxy]-ethyl ester, pyridin-2-ylcarbamic acid 2-[6-(5-isopropyl- pyidine-2-yl-sulphonylamino)-3- A (2-methoxy-phenoxy)-2,2"-bipyrimidin-4-yloxy]-ethyl ester, q pyridin-2-ylcarbamic acid 2-[5 -(2-methoxy-phenoxy)-6-pyridine-2-yl-sulph- 1 0 onylamino)-2,2"-bipyrimidin-4-yloxy]-ethyl ester, 11 pyridin-2-ylcarbamic acid 2-[5-(2-methoxy-phenoxy)-6-pyridin-3-yl-sulphon- VY ylamino)-2,2" -bipyrimidin-4-yloxy]-ethyl ester, VY pyridin-2 -ylcarbamic acid 2-[6-(5- tert-butyl- thiophene-2-yl-sulphonylamino)- 4 5-(2-chloro-5-methoxy-phenoxy)-bipyrimidin-4-yloxy]-ethyl ester , Yo ‎pyridin-2-ylcarbamic acid 2-[6-(5- tert-butyl- thiophene-2-yl-sulphonylamino)- 11 no 5-(2-chloro-5-methoxy-phenoxy)-bipyrimidin -4-yloxy]-ethyl ester, pyridin-2-ylcarbamic acid 2-[6-(5- isopropyl- pyridine -2-yl-sulphonylamino)- YA 5-(2-methoxy-phenoxy)-2 -(3-methoxyphenyl)- pyrimidin-4-yloxy]-ethyl ester, 14 ‎pyridin-2-ylcarbamic acid 2-[6-(5-isopropyl-pyridine -2-yl-sulphonylamino)- | 0 5-(2-methoxy-phenoxy)-2-methylsulphonyl-pyrimidin-4-yloxy]-ethyl ester, AR pyridin-2-ylcarbamic acid 2-[2-(1,3-benzodioxol-5-) yl)6-(S-isopropyl-pyridine 17 the lag -2-yl-sulphonylamino)-5-(2-methoxy-phenoxy)- pyrimidin-4-yloxy] -cthyl ester, YY pyridin-2-ylcarbamic acid 2-[5-(2-chloro-3-methoxy-phenoxy) (-6-(3-isopropyi- Tie pyridine-2-yl-sulphonylamino)-2-morpholin-4-yl-pyrimidin-4-yloxy]-ethyl ester, Yo pyridin-2-ylcarbamic acid 2-[5-( 2-methoxy-phenoxy)-6-(5-methyl-pyridine-2- ~~ Y1 yl-sulphonylamino)-2,2' -bipyrimidin-4-yloxy]-ethyl ester, l pyridin-2-ylcarbamic acid 2-[5-(2-methoxy-phenoxy)-6-(5-methyl-pyridine-2- YA yl-sulphonylamino)-2-morpholin-4-yl-pyrimidin-4-yloxy]-ethyl ester, YA pyridin-2-ylcarbamic acid 5-(2-chloro-5-methoxy-phenoxy)-6-(5-isopropy!l- Ye pyridine-2-yl-sulphonylamino)-2-morpholin-4-yl-pyrimidin-4 -yl-methyl ester, 3 pyridin-2-ylcarbamic acid 2-[6-(5-isopropyl-pyridine-2-yl-sulphonylamino)-5- ~~ YY (2-methoxy-phenoxy)-2-morpholin-4 -yl-pyrimidin-4-yloxy]-ethyl ester, YY pyridin-2-ylcarbamic acid 2-[6-(2,5-tert-butyl-thiophene-3-yl-sulphonyl- ve amino)-5-(2 -methoxy-phenoxy)-2,2-dipyrimidin-4-yloxy]-ethyl ester, Yo pyridin-2-ylcarbamic acid 2-[5-(2-methoxy-phenoxy)-6-(3,5-dimethyl- 1 isoxazolyl-4-yl-sulphonylamino)-2,2"-dipyrimidin-4-yloxy]-ethyl ester, A pyridin-2-ylcarbamic acid 2-[6-(5-tert-butyl-thiophene-2-yl-sulphonylamino) )- YA 5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yloxy]-ethyl ester, Ya Pyridine-2-ylcarbamic acid 2-[6-(2,5-dichloro- thiophene-3-yl-sulphonylamino) €. -5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yloxy]-ethyl ester, p-Pyridine-2-ylcarbamic acid 2-[6-(3,5-dimethyl) - isoxazolyl-4-yl-sulphon-ylami- 10)-5-(2-methoxy-phenoxy)-2-morpholin-d-yl-pyrimidin-d-yloxy]-ethyl ester. £y 1 - Compound according to claim no. ©; Whereas, the compound is furan-3-ylmethylester 2-[ 5-(2-methoxy-phenoxy)6-(5-methyl- Pyridine-2-sul- Y phonylamino)-2-morpholin-4-yl-pyrimidin-4 -yloxy]-ethyl ester. Y We C 1 - Compound of claim No. 6; Where the compound is 0 5-iert-butyl-thiophene-2-suiphonic acid 5-)2- methoxy-phenoxy)-6-[2-(3-pyr- ¥idin-2-yl-ureido)- ethoxy]-2,2'-dipyrimidin-4-ylamide, 3 ¢ 5 : 5-isopropyl-pyridine-2-sulphonicacid5-(2-methoxy-phenoxy)-6-[2-(3-pyridin-°) 2-yl-ureido)-ethoxy]-2,2'-dipyrimidin-4-ylamide. 1 -1 is a compound of the form: RS 1 kg 1107 N > m ) { ed Veo Y N = RT stands for R3 3 where RY is chosen from The group consisting of tpyridyl pyridyl substituted pyridyl subsituted © with the group that is selected from a lower-alkyl 1-halogen camino sual chalogen mono-sid JI lower-alkylamino-absorbent SEY di-lower-alkylamino and low-tlower-alkanyl A ¢pyrimidinyl pyrimidinyl subsituted with a choice of 4 group of lower alkyl halogen amino chalogen camino mono-lower-alkylamino mono-lower-alkylamino di-lower-alkylamino 1 lower-alkanyl furyl furyl furyl subsituted 0 One of the elements of the group consisting of a lower-alkyl halogen camino sisal <halogen 0 mono- lower- calkylamino " di-lower-alkylamino" and lower alkanyl lower-calkanyl 0 cthienyl and thienyl subsituted with a group to be chosen from a lower-alkyl amino size chalogen monoalkyl amino low Vo m cmono- lower-alkylamino 1V low di-alkylamino J ils di-lower-alkylamino YA low dower-alkanyl 14 select 182 from the group consisting of low alkyl hydrogens dower -alkyl 0 lower alkoxy JJower- alkoxy low alkyl TiO Jdower-alkylthio 7 lower alkoxy ¢lower- alkoxy- lower- alkyl alkylsulfonyl YY lower - alkoxy ¢lower- alkylsulphonyl -lower-alkoxy phenyl “lower-alkylphenyl Jud YY low ¢lower- alkylphenyl alkoxyphenyl ¢clower- alkoxyphenyl (addi a ¢ 0 low alkylenedioxyphenyl) ¢lower- alkylenedioxyphenyl low alkylphenyl lower ¢alkyl-phenyl Yo ¢Jower alkyl-phenyl-lower alkyl 71 lower alkoxy ©1077-phenyl Jt cphenyl-lower alkyl alkyl YY low alkyl dioxyphenyl lower alkyl lower YA pyrimidinyl pyridyl morpholino morpholino thiomorphilino piperidino su yu thiomorphilino YA and benzodioxolyl 5 ve is selected 18 of the group consisting of lower alkyl lower alkyl 1 lower clwer- alkoxy formyl halo - reduced alkyl chalo-lower alkyl vy hydroxy -lower alkyl chydroxyl-lower alkyl amino amino-lower alkyl ¥V low alkyl (CHy)p-O-¢(CHy)p-O-(CR'R®)OH ¢«CH,0-A- lower- alkyl .«(CHp)-O~(CR*RY);-Y-R® ¢«(CHy)m-O-(CR*R® NH, «(CR'R®),-OR' 4 vo is selected. Both RY and “18 from the group consisting of the 4-dower alkoxy chydrogen or the halogen TY RO are chosen from the group consisting of pyridyl pyrimidinyl ¢ pyrimidingl 4 tfuryl phenyl -phenyl substituted with a group to be chosen of a YA lower alkoxy lower alkoxy and a ¢halogen in both 8' and 8' is hydrogen hydrogen or a slower alkyl A 1 is ketalized 0 7-di oe Sy ma ethylene ketalized 1,2-dihydoxy tethylene > We : and Y is not chosen from the set consisting of “—0C(0)O - -NHC(OJNH- “OC(O)NH- £1 t NHC(0)O n to gt oY oY m equals 7 equals zero or 1 A 1) = the compound according to claim number VY where RY is chosen from the group X consisting of chydrogen pyrimidiny pyridyl morpholino Y thiomorphilino thiomorphilino piperidino 0106:0100 pyrrolidino ¢ benzodioxolyl alkoxy Jud lower- calkoxyphenyl 8 alkyl oi Subscript Jawer-alkylthio 1 8- Compound according to claim number VY where RC is a moiety chosen from “the group consisting of 27,011 covariates)-and.-.and-m-z"- © 7-8a-0 (0) The RO is chosen from the group consisting of Pyridel 5891M Pyramidiel & Alistentsturm and Fiorel 1SQR. -70 1 the compound of claim V4 where B® is -7-8, 0)021- and 7 is —0)C(0)0- 1 -"1 the compound bed of claim 71 where the compound is 0°: 5-isopropyl-pyridine-2-sulphonic acid [5-(2-methoxy-phenoxy)-2-mor- ~~ Y pholin -4-yl-6-[2-(pyrimiden-2-yloxy)-ethoxy]-pyrimidin-4-yl]amide. Y YY 1 compound according to claim number OY where 83 is hydroxy ethoxy V We: ‘ _— 4 m - YY 1 Compound according to claim no. (YY) where the compound is selected from the group TF which consists of: 5-isopropyl-pyridine-sulphonic acid [6-(2-hydroxy-ethoxy)-2-(3-methoxy- g) ‎benzyl)-5-(2-methoxy-phenoxy)-pyrimidin-4-yl] amide, ¢ 5-isopropyl-pyridine-sulphonic acid [6-(2-hydroxy-ethoxy)-2-(3-methoxy- 5) benzyl)-5-phenoxy-pyrimidin-4-yl] amide, 1 5-isopropyl-pyridine-2-sulphonic acid-[2-(3-methoxy- benzyl)-6-(2-hydroxy- no ethoxy )-5-phenoxy-pyrimidin-4-yl] amide, A which is TY*- the compound of claim number 1; 5-isopropyl-pyridine-2-sulphonic acid-[6-(2-hydroxy-ethoxy)-2-(3-methoxy- Y benz-yl )-5-(2-methoxy-phenoxy)- pyrimidin-4- yl]amide. 1 which is YY of bes compound number claim YO \ 5 -isopropyl-pyridine-2-sulphonicacid- [6-(2-hydroxy-ethoxy)-2-(3- Y methoxy-benzyl)-5-phenoxy-pyrimidin-4-yl] amide. 3 which is YY the compound of claim No. YY 1 5-isopropyl-pyridine-2-sulphonic acid-[2-(3-methoxy- benzyl)-6-(2-hydroxy- Y ethoxy)-5-phenoxy-pyrimidin-4-yl] amide. 3 Where 82 is selected from group 07 the compound according to claim number -71 \ phenyl-lower cower alkylphenyl consisting of low alkylphenyl Y — alkoxyphenyl - low dower-alkylpheny- lower alkyl lullah; Alkylphenyl - low ¥ Low - Alkyl Jud Dioxyl alkylpheny dJower-alkoxylpheny-lower alkyl ; Low alkyl pyrimidinyl istanestidrum pyridyl ¢lower alkygenedioxyphenyl-lower alkyl © Alg tpyridyl morpholino morpholino sthiomorphilino piperidino a pyrroidine and benzodioxolyl 1 4 ?- Pharmaceutical composition which includes: X 0) of ¥ mg to 0 milligrams of a compound of the formula: : RISO,NH Rt R?I : N . R2 ~ \ 0 RS v =« R7 y[ R3 ¢ ' is a heterocyclic selected from the group consisting of unsubstituted © rings of 2-furyl Joss Y pyrimidinyl «pyrimidinyl 7-pyridyl (2-pyridyl ¥— 1-pyridyl S3opyridyl 4-pyridyl 1 1,2- diazinyl linezide-1 1 «4- pyridyl ;- diazinyl -1, 4; “benzofuranyl benzotinyl cbenzothienyl 0 indolyl cindolyl purinyl ¢purinyl thiomorpholine cthiomorpholino 1 piperidine piperidine cquinolyl isoquinolyl and quinazolyl Y or the aforementioned single heterocycles Or double-substituted by 10-alkyl “Coy alkyl alkanyl” Cry halogen amino camino mono-alkylamine 4 bir or di-alkylamino Cy di-alkylamino Vo Selection 2p from the group that OST of alkyl hydrogen (Cry alkoxy hydrogen) is an alkyl tar of an alkoxy ben alkyl of 11-alkylsulphonyl 7-alkoxy “ phenyl J «Cy. alkoxy alkoxy VA©-phenyl; A 7-alkylenedioxyphenyl dioxygenase and a 4-non-homocyclic ring are selected from the group consisting of unsubstituted "-furyl-2" rings : A= Jor su Y 2-pyridyl “-epyrimidinyl 3-furyl ?-ofuryl 1 1,4- diazinyl 1 1,2- diazinyl diazyl = Yo) cd- pyridyl ? <- pyridyl 3-01 1 3- thienyl ?- thienyl 2- thienyl Jai “morpholino morpholine cdiazinyl VY thiazolyl 01 imidazolyl coxazolyl isoxazolyl isoxazolyl YY benzothienyl benz and ethyl “benzofuranyl benzofuranyl epyrrolyl pyrolyl imidazolyl Yi (piperidino su yu cthiomorpholino thiomorpholino purinyl purinyl cindolyl indolyl Yo heterocyclic squinazolyl quinazolyl isoquinolyl isoquinolyl cquinolyl quinolyl 1 Alkanoyl (Cp alkyl _ aforementioned, which is mono- or double-substituted by an alkyl 'mono-alkylamino' mono-alkylamino camino amino 'halogen' 'Cp alkanoyl YA' dialkylamino dialkylamino ' CigYq Cy. Alkoxy Alkoxy «Cy alkyl P 183 is selected from the group consisting of once alkyl hydroxyalkyl hydroxyalkyl «C7 haloalkyl halo alkyl formyl formyl 9 FV) - ««(CHy),-O -(CR*R®),0H “CH;0-A-C17 alkyl” C17 aminoalkyl alkyl sual YY from RY and to amygdala (...WRT); (CH)m-O-(CR*RONH, 0 ben and an alkoxy halogen is selected The group consisting of hydrogen YE < halogen + is a heterocyclic is selected from the group consisting of 187 TT pyrimidinyl 3-furyl *-furyl 2-furyl unsubstituted groups of ?-furyl vv 10 cdpyridyl ; 4-t morpholiner diazinyl 4-diazinyl 1” 1,2- diazinyl *?- diazinyl 4 10102011 imidazolyl cthiazolyl thiazolyl isoxazolyl 3-isoxazolyl thienyl 0 indolyl cbenzothienyl pyrrolid Azaharim Benzofuranyl 6020171 benzotenyl 1 quinolyl cpiperidino piperidino cthiomorpholino thiomorpholino cpurinyl purinyl cindolyl €Y or homo ring quinazolyl and quinazolyl isoquinolyl isoquinolyl £Y alkanoyl (Cry alkyl mentioned above which are mono- or di-substituted by an alkyl £4 mono-alkylamino camino amino chalogen halogen «Cy; alkanoyl © no -wm- Crp £7 or the “Cu and phenyl” substituted with a group to be chosen from the Cry alkyl AY alkoxy “Cy alkoxy” halogen and the alkyl “C1”. alkyl RY SR 3 where each separately is hudrogen or the alkyl Cop alkyl A £4 is JET 1 hydroxy-ethylene ketalized 1,2-dihydoxy tethylene 0 51 7 is selected from the set consisting of i 0-C(0)0- “NHC(0)O- + NH(CO)NH- “O(CO)NA- oY of “ equals J FY ); of « equals zero or 1; and 00 (7) is an inert carrier. 1 4- The pharmaceutical composition according to claim No. TA, which also includes inactive Y additives, cinert additives, binding compounds, cinders, cfillers, YF diluents, preservatives 5:; stabilizers emulsifiers and flavorants i flavorants | -00 1 Pharmaceutical composition which includes “0 (1) from ? milligram to 001 milligram of a compound of formula : 103 RY RS 0 I N Mala m 0" i N = R&R? 3 t where RY ° is chosen from the group consisting of a tpyridyl subsituted pyridyl 1 with the group chosen from a lower-alkyl halogen Yo a 1” 6mm cat camino sul lower-alkylamino mono-alkylamino -000; di +lower-aikanyl (addi a) di-lower-alkylamino (addi a tpyrimidinyl pyrimidinyl subsituted with group 1 selected from lower-alkyl halogen camino six halogen mono-alkyl 11-lower-alkylamino cmono-lower-alkylamino di-alkylamino-low 10-21 0 made of wah and low alkanoyl? One of the elements of the group consisting of a lower alkyl dower-alkyl halogen 014 amino camino monoalkyl Sl “mono-lower-alkylamino_saési a sisal 0 alkyl amino di-lower-alkylamino and alkanoyl Low Jawer-alkanyl enyl cthienyl VY 1 and thienyl subsituted with a selectable group of ddower-alkyl 7 low alkyl halogen camino sim. alkylamino A di-lower-alkylamino and low alkanyl Jdower-alkanyl 03 0 Choose 2 from group consisting of low alkyl hydrogen Jdower-alkyl 7 | low alkoxy clwer - alkoxy lower-alkylthio YY alkoxy- lower- alkyl -106; Low alkyl sulfonylu- YY low alkoxy «phenyl Jud ¢lower- alkylsulphonyl-lower-alkoxy alkyl Jus Vi low ¢lower- alkylphenyl dlower- alkoxyphenylaéai alkylene Yo dioxyphenyl low lower alkylenedioxyphenyl lower alkyl- phenyl 7 lower alkyl-phenyl-lower alkyl YY low alkoxy:©10-low alkyl phenyl cphenyl-lower alkyl YA lower alkyl talkylenedioxyphenyl lower alkyl lower pyrimidinyl ¥4 pyridyl “pyridyl” morpholino manufactured: 0; 1 ¢benzodioxolyl RP is selected from the group consisting of a lower alkyl YY lower alkoxy formyl halo-lower alkyl <halo-lower alkyl Woe _1y— amino-lower chydroxyl-lower alkyl vy (CHa) 0-¢(CHy)-0-(CR*R)nOH «CH0-A- lower- alkyl low alkyl calkyl ‎;? ~(CHp)m-O-(CR*R?),-Y-R' «(CH)m-O-(CR'R")NH: Uncle Damn Yo Both RY and RY are chosen from the group consisting of a lower alkoxy hydrogen-hydrogen or a thalogen A RY is chosen from the group consisting of pyridyl ¢pyrimidinyl 3-furyl ¢furyl | phenyl - phenyl substituted with a group to be chosen of a 0 low-door alkyl alkoxy and a halogen | slower alkyl or low alkyl hydrogen each of 2 and alkyl is hydrogen 1 ketalized 1,2-dihydoxy SEY 1 YS is A for : | sethylene ¢V - —OC(0)0 From the group consisting of Y select 21 NHC(0)O- t -NHC(O)NH- «OC(O)NH- ~~ 0 £1 " equals 7 - " or ;; and 31 ““ is zero or 1; f: M (Y) is an inert solder. £9 1 1 ?- the composition according to claim no. os wherein it includes the composition according to of claim number oY since the composition includes yo milli" of the compound of formula 1. YY 1 The composition according to claim No. Fe where the composition includes * milligrams of Y the compound of formula 1. YE 1 Pharmaceutical composition lag of Claiming No. (Fr) which also includes additives 1 cinert additives lala ¥ binding compounds LS ya ¢binders fill: 5116; Diluents V Preservatives 8m Cstabilizers Emulsifiers 638 Flavorants ~~ ¢ : Fe) Method for treating disorders associated with vasoconstriction including 1" high blood pressure hypertension blood retention It can be used without vasospasm ¥ and angina pectoris, and this method includes giving the patient who suffers from this disorder an impressive amount of a compound with the formula: RY RS 1 10 N Z: 3 \ ed N = |R7 | cat 13h" where L is a heterocyclic ring chosen from the group consisting of A unsubstituted rings of ?- 2-furyl pyrimidinyl ?- pyridyl-2 «pyridyl 4 "-pyridyl 2-pyridyl “pyridyl -4;0"-diazinyl -1,2 1 0 0 ;-diazinyl -1 ,4; morpholino “morpholino ?thienyl -2” ?-thienyl 1)-¢3 isoxazolyl “isoxazolyl” oxazolyl “thiazolyl” VY imidazolyl cimidazolyl pyrrolyl benzofuranyl cbenzothienyl 0 indolyl cindolyl purinyl ¢purinyl thiomorpholino 4 piperidino quinolyl isoquinolyl and quinazolyl Vo or non-rings The preceding congener SA is mono- or di-substituted by an alkyl «Cy. alkyl alkanoyl “Cy halogen” camino six chalogen mono-alkylamino “Cy. WY” or di-alkyl amino “Cry YA” RP is selected from the group consisting of alkyl chydrogen C17 alkyl i.e D 14 Alkoxy Cy alkoxy alkyl fer ger alkoxy ben alkyl “Crs 0 alkyl alkyisuiphonyl Ja sil 7-alkoxy bertville” phenyl alkoxy 71 © - vinyl; A Cy alkylenedioxyphenyl and a TY non-homocyclic ring selected from the group consisting of unsubstituted rings of ?-furyl-2 cfuryl YY 7-furyl 3-furyl pyrimidinyl 7-pyridyl 2 -pyridyl “-pyridyl 3opyridyl 05 4 -pyridyl 1” 4-pyridyl ?- diazinyl 0 ¢1,2- diazinyl 4-diazinyl-1,4 “diazinyl Yo morpholino 7 thienyl 2-7-thienyl 3-13 isoxazolyl coxazolyl thiazolyl cthiazolyl imidazolyl dimidazolyl 1 pyrrolyl benzofuranyl benzothienyl YA Indolyl cindolyl purinyl <purinyl thiomorpholino cthiomorpholino piperidino “piperidino YA quinolyl cquinolyl isoquinolyl and quinazolyl heterocycle” 0 previously mentioned which is mono- or di-substituted By alkyl (Ci alkanoyl 1) halogen amino camino mono-alkylamino “Cp VY” or dialkyl “C7 dialkylamino sie vy 183 is selected From the group consisting of the “Cy alkyl” alkoxy Cy. alkoxy VE; formyl haloalkyl «Cy haloalkyl hydroxyalkyl hydroxyalkyl gar To aminoalkyl (C 1,7 aminoalkyl alkyl tatate +(CHy)y-0-(CR'R"),0H - ‎ (CHp)m-O-(CR'RONH, 1 5 l) 0 r) ?; RY is chosen from _ the group consisting of alkoxy chydrogen b and two halogens: <halogen Y'A ke RY 4 3 for a heterocycle chosen from the group consisting of 0 unsubstituted groups of ?-furyl 2-furyl ?-furyl 3furyl cpyrimidinyl 56 "-pyridyl 2-pyridyl ?-pyridyl (3-pyridyl; -pyridyl nm-4 10 5"-diazinyl 1¢1,2- diazinyl 4-diazinyl -¢1,4 morpholiner —Y (morpholino _thienyl 3-isoxazolyl thiazolyl cthiazolyl imidazolyl inradhamsen £8 pyrrolyl benzofuranyl benzofuranyl benzothienyl indolyl . —1 i quinolyl piperidino su yu ¢thiomorpholino thiomorpholino cpurinyl purinyl cindolyl 8 or the heterocyclic “quinazolyl” and isoquinolyl cquinolyl: an alkanoyl (Cp alkyl male) which is mono- or di-substituted by an alkyl AGL EY mono-alkylamino camino amino chalogen halogen «Cp; alkanoyl 4 «Cp. an alkyl substituted with a group to be chosen of the alkyl phenyl Judy «Cry» or the £9 alkyl ber and an alkyl halogen ber©; alkoxy halogen Os “Cy.7 alkyl or alkyl hudrogen where each separately is hydrogen R® Thru 51 Ketalized 1,2-dihydoxy ethylene ou Sy ma SEY) is a ketalized A oY sethylene oY ; ~0-C(0)0- A is selected from the set of NHC(0)O- +NH(CO)NH- “O(CO)NH- mm set J YY is equal to 1.5 is equal to zero or “ov” as the effective amount ranges from about FO (method of claim)* - 1 mg/kg body weight per day. 001 to about 1” v A method for treating disorders related to vasoconstriction is chosen from YY 1 blood retention and constipation <hypertension The group consisting of high blood pressure Y and angina pectoris 8 It includes giving the patient who has vasospasms Sle ll spasm * - He suffers from this disorder a significant amount of a compound of the formula RISO:NH !k RS? [ N 0 RZ ~{ \ 6 RS 3 N = Rr? cat R7 1: 1 where L is chosen from the group consisting of a fpyridyl substituted pyridyl Jower-alkyl group which is selected from low alkyl pyridyl 40 A 4 halogen «uncle 1 cat; camino sis mono-lower-alkylamino 0 di-lower-alkylamino and lower alkanyl ¢lower-alkanyl 11-pyrimidinyl pyrimidinyl substituted subsituted with a selection of 0 lower-alkyl halogen camino six chalogen mono-lower-alkylamino mono-lower-sual alkyl halogen alkylamino 4 and low alkanyl tinter-alkanyl furyl cfuryl furyl substituted furyl subsituted 0 with one of the group consisting of a low alkyl cJower-alkyl halogen ¢halogen Y1 amino camino monoalkyl amino low “mono- lower-alkylamino = 11 sud alkyl lower di-lower-alkylamino and lower-alkanyl cthienyl YA and de gana thienyl subsituted are selected from lower alkyl clwer-alkyl 3 halogen camino sisal halogen mono- a door-alkylamino di-lower-alkylamino and lower alkanyl <lower-alkanyl 71 | YY 13 are selected from the group consisting of lower alkyl hydrogen 0" lower alkyl lower alkoxy lower-alkoxy lower alkyl fero-alkylthio lower alkoxy - low alkoxy- lower- alkyl -©©100;lower-alkylphenyl-lower-alkoxy ve phenyl J ¢lower- alkylsulphonyl-lower-alkoxy alkyl Ji 1 lower ¢lower- alkoxyphenyl (sedi a Jad Alkytin VY Lower-alkylenedioxyphenyl phenyl-lower alkyl- YA Slower alkyl-phenyl-lower alkyl 4 Low Jui— lower alkoxy phenyl-lower alkyl Ye low alkyl talkylenedioxyphenyl lower alkyl lower pyrimidinyl pyridyl pyridyl morpholino tmorpholino ¢thiomorphilino CE tbenzodioxolyl and benzodioxolyl tpiperidino sham TY dower alkyl From the group consisting of low alkyl RP Ty halo-lower alkyl formyl dower- alkoxy low vie amino is selected -lower amino-low alkyl chydroxyl-lower alkyl vo (CHa) O-¢(CHy),-O-(CR*RY)mOH (CH,0-A- lower- alkyl alkyl Low alkyl ¥1 º ~(CHy)m-O-(CR*R®)y-Y-R' «(CH2)m-O-(CR*R")NH, ((CR*R®),-OR' TV hydrogen ‏ From the group consisting of hydrogen RY RY TA ¢halogen or lower alkoxy halogen va pyrimidinyl epyridyl is selected From the group consisting of pyridyl RY 5-phenyl is selected substituted with a group to be chosen of a phenylfuryl alkyl 1(¢pyrimidiny] 3 thalogen and a dower alkoxy halogen EY lower alkyl or a low alkyl hydrogen that is R” Either 187 and ketalized 1,2-dihydroxy (SHY) are catalized A § ¢ tethylene £0 - —OC(0)0 ¥ is chosen from the group of 3 NHC (0)O s-NHC(O)NH- “OC(O)NH- 699 gf JV CY “is equal to 1 £A equals zero or “£4 as the effected quantity varies from TV depending on the method for claim No. -©* 1 mg/kg body weight per day. Where the compound is selected from group SY 1 consisting of: (AY 5-Isopropyl-pyridine-2-sulphonic acid 5-(2-chloro-methoxy-phenoxy)-6-meth ÷ yl-2-morpholin -4-yl-pyrimidin-4-ylamide, £ We : —y— 5-(2-chloro-5 -methoxy-phenoxy)-6-formyl -2-morpholin-4-yl-pyrimidin-4-yl e amide 1 5-isopropyl-pyridine-2-sulphonic acid 5-( 2-chloro-5-methoxy-phenoxy)-6-l hydroxymethyl-2-morpholin-4-yl-pyrimidin-4-ylamide , A : 5-isopropyl-pyridine-2-sulphonic acid 5-(2- chloro-5-methoxy-phenoxy)-6- 5 chloromethyl-2-morpholin-4-yl-pyrimidin-4-ylamide, 01 5-(2-chloro-5-methoxy-phenoxy)-6-(2-hydroxy- ethoxymethyl)-2-morpholin-4-11 yl-pyrimidin-4-ylamide. VY