MXPA94007369A - Novel deoxy and oxygen-substituted sugar-containing 14-aminosteroid compounds - Google Patents

Abstract

Deoxy and oxygen-substituted sugar-containing 14-aminosteroid compounds and the pharmaceutically acceptable acid salts or esters thereof of general formula (I), wherein a) R1 is (i) COOR5, where R5 is a 1-6 carbon lower alkyl group;a 1-6 carbon lower alkyl group substituted by an amino group;an arylalkyl or heteroarylalkyl group or a carbocyclic ring, or (ii) CHR6OH, where R6 is a hydrogen atom or a 1-6 carbon lower alkyl group, or (iii) COR''', where R'''is hydrogen;1-6 carbon lower alkyl;1-6 carbon lower alkyl substituted amino;amino or dialkylamino, and b) R2 is -NR7R8;where R7 and R8, which may be the same or different, are hydrogen atoms or 1-6 carbon lower alkyl group, and c) R3 is (i) a deoxy or oxygen-substituted monosaccharide sugar residue, (II) wherein R9a, R9, R10, and R10a, which may be the same or different, are 1-6 carbon lower alkyl;hydrogen;hydroxy;fluorine;alkoxy;acetoxy;arylalkyloxy;or benzoxy;R11 is 1-6 carbon lower alkyl;hydrogen;hydroxy;fluorine;benzoxy;arylalkyloxy;heteroarylalkyloxy;acetoxy or alkoxy;wherein further when R5 is 1-6 carbon lower alkyl;either R9, R10, or R11 cannot be hydroxy or acetoxy;further provided that when R9a is hydrogen and R10a is hydrogen and R9 is hydrogen;hydroxy or acetoxy;and R11 is hydroxy;acetoxy or alkoxy;R10 cannot be hydroxy or acetoxy;and R12 is methyl;acetoxymethyl or hydroxymethyl;t can be a single or double bond, or (ii) a deoxy or oxygen-substituted monosaccharide sugar residue, (III) wherein R11 is arylalkyloxy;heteroarylalkyloxy or 1-6 carbon lower alkyl substituted oxosilane and R12 is methyl, and d) R4 is (i) OH, or (ii) H, or (iii) OR13, where R13 is a monosaccharide sugar residue;acetoxy;benzoxy;arylalkyl or heteroarylalkyl, and e) Z is (i) -CH-, where a and b are single bonds, or (ii)=C, where either a or b is a double bond.

Description

COMPOUNDS 14-AMINOESTEROIDS NOXIOUS DESOXY AND OXYGEN- SUBSTITUTE CONTAINING SUGAR Song Liu David E. Portlock Gilies Y. Genain Jean J. Koenig Jacques de Rostolan Randy S. Mu BACKGROUND OF THE INVENTION This invention relates to novel 14-aminoesteroid compounds deoxy and oxygen substituted. The present invention also relates to pharmaceutical compositions containing these novel compounds as well as a method for the treatment of Congestive Heart Failure (CHF) using the compounds of the present invention.

CHF is a progressive disease where the heart becomes increasingly less able to provide adequate cardiac output (CO), which is the volume of blood that the heart pumps with respect to time, to -? bring oxygenated blood to peripheral tissues. When the heart fails initially, the rest of the body compensates for the loss of CO and such compensation mechanisms eventually result in the syndrome known as CHF. As CHF progresses, structural damage and damage occur. Such structural damage manifests macroscopically as a ventricular hypertrophy in the myocardium, and microscopically as a z-interstitial, perivascular and replacement fibrosis in the wall of the ventricle, decreased density of myocardial capillaries and death of myocardial cells. When fibrosis of the myocardial tissue occurs, it compromises the heart functioning because remnant viable myocardial cells have a larger workload. I have only oddly, in the failing heart, the ability to develop strength during systole (phase in the cardiac cycle during which the expulsion of -? blood from the ventricles) is reduced. In this way, a greater diastolic-end volume is needed (during the diastolic phase of the cardiac cycle the ventricles are filled) to perform any level of external work. In heart failure, reduced expulsion, caused by a disproportion between capacity and workload, results in an increase in final diastolic pressure and pulmonary capillary pressure. They follow him and constantly pulmonary congestion and peripheral edema. From the perspective of the patient, while CHF progresses, he experiences increased worsening of the symptoms of fatigue and dyspnea. rf * Effective treatment of CHF requires a determination of its etiology, if possible, as some etiologies of CHF have their own unique form of treatment. CHF has a variety of etiologies, including myocardial diseases such as coronary artery disease or myocarditis; valve diseases such as mitral valve prolapse or aortic aortic stenosis; pericardial diseases; - congenital heart disease; pulmonary disease, cardiac arrhythmias, hypertension and diabetes. For example, if the etiology of CHF is myocarditis or an arrhythmia, then treating the patient with an antimicrobial or an antiarrhythmic agent, respectively, can restore patient A to normal cardiac function. However, once the etiologies that do not respond to other treatments are ruled out, treatment is initiated by one or more of three modalities; 1) the pumping capacity of the heart is improved by administering an inotropic agent, such as digitalis, 2) the workload of the heart is reduced by rest and / or by the administration of vasodilators such as captopril and 3) the retention of water and sodium is controlled by a diet low sodium or the administration of a diuretic such as thiazide. The treatment of CHF is individualized according to the symptomology of the patients and the tolerance for certain medications. For example, some patients may have a strong tendency to develop digitalis intoxication, while other patients with mild symptoms may benefit from diuretics, which have a higher therapeutic index. Moreover, current wisdom suggests that diuretics are an appropriate first-line therapy for CHF and that treatment with diuretics should be followed by sr.) And the treatment with vasodilators and digitalis. It has also been observed that digitalis is the most effective in patients suffering from severe CHF. See generally, Braunwald, Heart Disease: A Textbook of Cardiovascular I joined. Vol. (3rd ed. 19 & amp;), Chung, E.K., Quick Reference to Cardiovascular Disease, Chapter 27 (2nd ed. 1963) and Fowler, N.O., Cardiac Diagnosis and Treatment. Chapter 12 (2nd ed 1976). «And * While digitalis is useful to diminish the symptoms associated with the odinámicos problems characteristic of severe CHF, its low therapeutic index, indeed. limits its therapeutic utility. See generally, Braunwald, Heart Disease; A Textbook of Cardiovascular Medicine. Vol. (3rd ed. 1966), Chung, E.K. , Quick Reference to Cardiovascular Disease, chapter 27 (2nd ed.1963), Fowler, N.Q., Cardiac Diagnosis and Treatment. Chapter 12 (2nd ed. 1976) and Goodman and Bilman, The Pharmacological Basis of Therapeutics. Chapter 3 > + (6th ed., 1990). The toxicity problems associated with digitalis have prompted researchers to try to develop safer cardioactive compounds. Cardioactive compounds containing steroidal nuclei have been described in the following patents: World Patent Publication WO 67/04167 to Chiodini, et al., Published on July 16, 1967 discloses steroid d aminoglycoside derivatives substituted by a non-toxic residue. in position 3 and an acetal bond in position 14-, the description states that the compounds are useful for the treatment of hypertension. The French patent 2,642.97 of Guiña published on August 17, 1990 describes a composite similar to digitalis, 2,3-dioxymethyl-6-met il-3-beta-D glucose-strophanthine, which contains a substituted steroid nucleus. in position 3 with a glucose portion and in * position 17 with the lactone portion and in position 14 with a hydroxyl group. The description states that the compound is useful in the prevention of pathological conditions resulting from the cardiac insufficiencies for which it prescribes digitalis and in the prevention of pathological conditions resulting from hypertension due to arterial calci cation. It is considered that the compound d Guiña is a positive inotrope, a peripheral vasodilator an antiarrhythmic agent. Mundia Patent Publication W0 67/04166 to Chiodini et al., July 16, 1967, discloses a steroid aminoglycoside having an amino-substituted alkylamino sugar in the 3-position such as 2-amino or 2-alkylamino-2-deso i-hexapiranssi residues. it, 3-amino or 3-alkylamino-3-deacy-hexo-pyrasposyl, 3-amino or 3-alkyl-amino-3,6-dideoxy-hexopyranosyl, 3-amino or 3-alkylamino-2,3,6-trideoxy-hexopyranosyl , 4-amino or 4-alkylamino 10 2,4,6-trideoxy-hexopyranosyl and a cyclic amide (lactam) in position 17. Position 14 is substituted with a hydrogen. It is said that the compound is useful as hypertensive. World Patent Publication WO 91/17176 to Enpy, et al., Published November 14, 1991, discloses a steroid glycoside useful as a blood pressure-increasing agent, having a sugar moiety in the 3-position, such as pentose, hexose or combinations thereof and a lactose ring at position 17, position fc 14 is replaced with an OH, H or F, Cl, Br or NH-2 group; and DD 296502 A5 to Siemman, et al., issued December 5, 1991, describe a steroid amide to treat heart failure where position 3 is replaced with a sulfonyl amino group and position 17 is replaced with a lactone ring of 5 or or members; position 14 is replaced with a hydroxy group. The patent of E.U.A. 5,144,017 to La Bella, September 1, 1992, discloses steroid compounds that are said to be useful as cardiac stimulators wherein position 3 is replaced with a glycoside radical such as a β-D-glucoside, α-rhamnoside, tridigitoxoside and position 17 it is substituted with an acetoxy group or an amino group; position 14 has a hydroxy group; and the patent of E.U.A. 5,175,261 to McCall, on December 29, 1992 describes pyrimidini lp iperaz inila steroids compounds useful in the treatment of spinal trauma, cephalic injury and pain. subsequent cerebral vasospasm, preventing damage following cardiopulmonary resuscitation and cardiac infarction where position 3 is hydroxy, CH30, COOH, or bensoxy, position 14 is a hydrogen, and position 17 is a heterocyclic amine. DD 256,134 Al a Wunderwald, et al., Granted • on April 27, 1966 discloses a method for making cardioactive esteorides wherein the 3-position of the steroid molecule is replaced with a morpholinoformilox residue i, and the 17-position of the steroid molecule is replaced with a lactone ring; position 14 is replaced with hydroxy, hydrogen or an olefin. It was considered that said compounds are useful for increasing cardiac contractility. JP 4-290699 to Ichikawa, et al., Open to the public on October 15, 1992, discloses a coded cardiotonic steroid wherein position 3 of the steroid nucleus is replaced with an oligosaccharide; wherein said oligosaccharide further consists of three glucopyranosyl portions 1 and position 14 is replaced with an OH group, and position 17 is replaced with a lactone ring. Templeton, etal., 36 3. Med. Chem. 42-45 (1993) describes the synthesis of derivatives of 14-h idroxi-21-nar ~ 5β, 14β-pregnane and 5β, 14β-pregpane, «-L-rhamnosides of C-3 and tris-ß-D-di thioxides. It is reported that these compounds are effective cardiac icos. These derivatives, which possess a C-17ß group C0CH-? 0H, CH ^ OH, COasMe, CHSBNH-J. 0 CH ^ NOa,, join the recognition site 12 cardiac muscle digitalis receiver. Templeton, e al., 1 3. Chem. Sci. Perkin. Trans .. 2502-2517 (1992) describes the synthesis of 20ot- and 20ß- cetamido-, amino-, nitr and hydroxy-3-glucoside (aL-rhamnopyranoside and tris-β-D digitoxoside) and genin derivatives of 14- hydroxy-5β, 14β pregnane together with the oxime of C-20, hydrazone amidinohydrazona. It is determined that these compounds are effective cardiotonics. Adeoti, 3. B., et al., 1 Tetra edrop Letters, 3717-3730 (1969) describes a method for introducing a 14β-amino function within a steroid molecule. Said method allows the preparation of 14β-amino 5β-pregnane-3β, 20β cardioactive diol. Additionally, it is shown that inhibitors of angiotensin converting enzyme (ACEI) reduce mortality in CHF pats. See, Nicklas, 3. M. Pitt, B. et al., (The SOLVD Ipvest igators), "Effect or Enalapril on Survival in Pats with Reduced Lef Ventricular Ejection Fractions and Congestive Heart Failure" N. Engl. 3. Med. 325 (5): 293 (1991). However, four million people still suffer from CHF. Mortality 5 years after the diagnosis of CHF is 60.% for men and 45 for women. This is a clear indication that they need better therapies directed towards the treatment of CHF. See, Parmley, W.W., "Pathophysiology and Curren Therapy of Congestive Heart Failure", 3. Am. Col. Cardiol. 13 13: 771-765 (1969); Francis, G.S. et al., "Copgestive Heart Failure: Pathophysiology and Therapy", Cardiovascular PharmacoloQv, 3rd Editiop (1990). It has been shown that 14-aminoesteroid compounds are useful in the treatment of CHF by incerenergizing cardiac contractility. These compounds provide the therapeutic benefit of increased cardiac contractility without the side effects of digitalis. These 14-aminosteroids are described in the following three patents, all incorporated herein by reference: US patent. 4,552,666, Jarreau, et al., Issued November 12, 1965; patent of E.U.A. 4,564,269, Oarreau, et al., Issued April 22, 1966 and; patent of E.U.A. 4,665,260, Jarreau, et al., Issued December 5, 1969. These three patents describe compound 14-aminosteroids possessing positive inotropic activity. S has now discovered that the 14-aminoesteroid compounds of % the present invention, wherein the 3-position is substituted with a deoxy portion and an oxygen-substituted sugar moiety, are more effective inotropes. Said 14 sugar-substituted deoxy and oxygen aminoesteroids are more resistant to metabolism and therefore provide a longer inotropic activity than the 14-aminosteroids of the prior art. 14 BRIEF DESCRIPTION OF THE INVENTION Deoxy and oxygen-substituted 14-aminoesteroid compounds and pharmaceutically acceptable esters or esters thereof of the general formula: where COORa, wherein R a is a lower alkyl group of 1-6 carbon atoms; a lower alkyl group of 1-6 carbon atoms substituted by an amino group; an arylalkyl or heteroarylalkyl group or a carbocyclic ring, or (ii) CHR? OH wherein R? is a hydrogen atom or a lower alkyl group of 1-6 carbon atoms, or (iii) COR '' ', wherein R' '' is hydrogen; lower alkyl of 1-6 carbon atoms; amino, lower alkyl of substituted CX_A; amino or dialkylamino and b) Ras is -NR7R? wherein R-, and Rβ, which may be the same or different, are hydrogen atoms or lower alkyl groups of 1-6 carbon atoms, and c) R3 is (i) a monosaccharide deoxy or substituted oxy residue, wherein R ^ -R "y, R10 and IO * 1 ° S which may be the same or different are lower alkyl of 1-6 carbon atoms; hydrogen; hydroxy; fluorine; alkoxy; acetoxy; arylalkyloxy benzoxy; R ^ is a lower alkyl of 1-6 carbon atoms; hydrogen; hydroxy; fluorine; benzoxy; Arylalkyloxy; heteroarylalkyloxy; acetoxy or alco? i; wherein further when Rs is a lower alkyl of 1-6 carbon atoms, R ^, R10 RJLA can not be hydroxy or acetoxy; with the condition 16 further that when •? - - is hydrogen, Ri »is hydrogen, R ^ is hydrogen; hydroxy or acetoxy and R? a. it is hydroxy, acetoxy or alkoxy, R10 can not be hydroxy acetoxy; Ria, be methyl; aceto? imetyl or hydroxymethyl; can be a single or double bond, or (ii) an oxygen-substituted deoxy monosaccharide residue wherein RiA is arylalkyloxy, substituted Ci-a heteroarylalkyloxy, Rxs is methyl (i) OH or (ii) H, or (iii ORxs where Ria is a monosaccharide residue, acetoxy, benzoxy, arylalkyl, heteroarylalkyl and e) Z is 17 (i) -CH- where a and b are single bonds or, (ii) = C where a or b is a double bond.

DEFINITION AND USE OF TERMS The following is a list of definitions for the terms used in the present invention. "Arainosteroid" is a steroid ring compound that has an amino group in the steroid nucleus. "Alkyl" is an unsubstituted or substituted, straight-chain or branched chain saturated hydrocarbon chain having from 1 to 6 carbon atoms, preferably unless otherwise indicated, from 1 to carbon atoms. Preferred alkyl groups include but are not limited to methyl, ethyl, propyl, isopropyl butyl; a monovalent radical derives from an aliphatic hydrocarbon by the removal of a hydrogen atom; such as methyl. A lower alkyl group contains 1-6 carbon atoms. "Heteroalkyl" as used herein is an unsubstituted or substituted saturated chain having 3 members and comprising carbon atoms and one or heteroatoms. "Alkenyl" is a n-substituted or substituted, linear or branched hydrocarbon chain having 2 6 carbon atoms, preferably 4 carbon atoms, and having at least one olefinic double bond. "Alkynyl" is an unsubstituted or substituted hydrocarbon chain having from 2 to 6 carbon atoms preferably from 2 to 4 carbon atoms and having at least one triple bond. "Acetate": a salt of acetic acid containing the radical CHACOO- "Acetoxy": Acetyloxy. The radical CH3COO- "Aglycone": that component of a glucoside, e.g. vegetable pigment, which is not a sugar. "Carbocyclic ring" or "carbocycle" as used herein is a saturated, unsaturated or substituted, saturated or aromatic hydrocarbon ring generally containing 3 6 atoms, preferably 5 atoms. "" Heterocyclic ring "or" Heterocycle "as used herein is an unsubstituted substituted, saturated, unsaturated or non-aromatic ring which comprises carbon atoms and one or more heteroatoms in the ring. Heterocyclic rings generally contain d 3 to 6, preferably 5 to 7 atoms. Unless otherwise indicated, the heteroatoms may be independently chosen from nitrogen, sulfur, and oxygen. 19"Aryl" is an aromatic carbocyclic ring. Aryl groups include, but are not limited to, phenyl, toluyl xylyl, cu enyl and naphthyl; an organic radical derived from an aromatic hydrocarbon by the removal of an atom; v.gr. phenyl from benzene. "Heteroaryl" is an aromatic heterocyclic ring Preferred heteroaryl groups include, but are not limited to, thienyl, furyl, pyrrolyl, pyridinyl, pyrazinyl oxazolyl, thiazolyl, quinolinyl, pyrimidinyl tetrazolyl. "Alkoxy" is an oxygen atom having a hydrocarbon chain substituent, wherein the hydrocarbon chain is an alkyl or alkenyl (e.g., -O-alkyl or O-alkenyl); an alkyl radical attached to the remainder of the molecule by oxygen, such as methoxy. Preferred alkox groups include, but are not limited to, ethoxy, ethoxy propoxy and alkyloxy. "Hydroxyalkyl" is a substituted hydrocarbon chain having a hydro? I substituent (e.g. -OH), may have other substituents. Preferred hydroxyalkyl groups include, but are not limited to hydroxyethyl, hydroxypropyl, phenylhydroxyalkyl. "Carboalkyl" is a substituted hydrocarbon chain having a carboxy substituent (eg, -COOH) may have other substituents. The carboxyalkyl groups preferred include carboxymethyl, carboxyethyl and their acids and steres. "Oxosilane" is a unit of oxygen and silicone that is repeated Si-Q-Si-O-, also known in the "siloxane" technique. "Aminoalkyl" is a chain of hydrocarbons, (eg, alkyl) substituted with an amino moiety (eg NH alkyl), such as dimethylaminoalkyl. "Alkylamino" is an amino moiety having one of two alkyl substituents (eg, N-alkyl). "Alkenylamino" is an amino moiety having one or two alkenyl substituents (eg, N-alkenyl). "Alkynylamino" is an amino moiety having one or two alkynyl substituents (eg, N-alkynyl). "Alkylimino" is an amino moiety having one or two alkyl substituents (eg, N = alkyl-). "Arylalkyloxy" is an oxygen atom having a substitute alkyl aryl, v. gr. phenylmethoxy phenylmethenoyl? i. 21"Heteroarylalkyl" is an oxygen atom having a "heteroalkyl" substituent, e.g.

"Arylalkyl" is an alkyl portion substituted with an aryl group. Preferred arylalkyl groups include benzyl and phenylethyl. "Heteroarylalkyl" is an alkyl portion substituted with a heteroaryl group. "Arylamino" is an amino moiety substituted with an aryl group (eg, -NH-aryl). "Aryloxy" is an oxygen atom having an aryl substituent (eg, -O-aryl). "Acyl" or "carbonyl" is a portion formed by removing the hydro group from a carboxylic acid (eg RC (= 0) -> Preferred alkylaryl groups include, but are not limited to, acetyl propionyl and butanoyl "Acyloxy" is an oxygen atom having an acyl substituent (eg, -O-acyl), for example, 0-C (= 0) alkyl. 22"Acylamino" is an amino moiety having an acyl substituent (eg, -N-acyl); for example, -NH- (C = 0) alkyl. "Benzoxy": the benzoyloxy radical "Bepzoyl": the aryl radical, CAHBCO-, derived from benzoic acid. "Benzoyl? I": v. gr. bepzo? i. The CAHsCOO radical derived from benzoic acid. "Carbamate": a salt of carbamic acid. This contains the radical -NCOa-, also known in the art as urethanes or carbamate esters. "Carboxi": prefix indicating the acidic carbohydrate group. "Ester": an organic salt formed from alcohol (base) and an organic acid by eliminating water; functional groups derived from carboxylic acids are those compounds that are converted into carboxylic acids by simple hydrolysis. The most common derivatives are esters, in which the hydroxy group is replaced by an alkoxy group.

OR RC-OR 23"Glucoside"; a natural compound of a sugar with another substance, which hydrolyzes a sugar plus an active principle: (eg coniferin produces glucose plus coniferyl alcohol) as the active ingredient; glucosides produce glucose, fructosides produce fructose, galactose produce galactose, etc .; the cyclic acetal of a carbohydrate. "Halogen" or "halide" is an atom or radical of chlorine, bromine, fluorine or iodine. The preferred halides are chlorine, bromine and fluorine. "Lactone": any of a class of inner esters of hydrocarboxylic acids formed by the loss of a water molecule from the hydroxy and carboxyl groups of the acids, characterized by the carboxyl-oxy-OCO- group in a ring, and Gasified according to the position of the hydroxyl group of the acid of origin. A "pharmaceutically acceptable" salt is a cationic salt formed in any acidic group (eg, carboxyl) or an anionic salt formed in any basic group (eg, amino group). Many such salts are known in the art, as described in the World Patent Publication WO 67/05297, Johnston et al., Published September 11, 1967 incorporated herein by reference. Preferred cationic salts include the alkali metal salts 24 (such as sodium and potassium), and alkaline earth metal salts (such as magnesium and calcium). Suitable anionic salts include halides (such as chloride), as well as carboxylates (such as maleate). Preferred apionic salts include the maleate. "Salts": substances produced from the reaction between acids and bases; a compound of a metal (positive) and a non-metallic (negative) metal: M-OH (base + HX (acid) = MX (salt) + Ha0 (water). "Steroid nucleus": generic name for a family of compounds lipids comprising bile acid sterols, cardiac glycosides, saponins and sex hormone.

"Substituent": any atom or group qu replaces the hydrogen of a compound of origin. "Substitute": replace an element or radical in a compound with a substituent.

* "Replaced": pertaining to a compound that has undergone a substitution. "Substitution": a reaction in which an atom or group of atoms in a molecule (usually organic) is changed by another. Substituent groups can substitute themselves. Such substitution may be with one or more substituents. Such substitutions include, but are not limited to, those listed in C. Hansch and A. Leo, * Substituent Constants for Correlation Analysis in Chemistry and Biology (1979), incorporated here for your reference. Preferred substituents include, but are not limited to alkyl, alkenyl, alkoxy, hydroxy, bear, amino, aminoalkyl (eg amino and ilo, etc.) cyano, halogen, carboxy, alkoxyacetyl (eg carboethoxy, etc.). ), thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl (eg piperidinyl, morpholinyl, peperazinyl, pyrrolidinyl, • etc.), imino, thioxo, hydroxyalkyl, aryloxy, arylalkyl combinations thereof. A "monosaccharide" is an individual portion of sugar; v. gr. hexose, 2-deoxyglucose, 6-deoxyhexose, 2,6-dideso? iheose, etc. rhamnose, glucose, arabinose, digitoxose, fructose, galactose; Iranian, hexopyranose, 6-deoxyglucose, 4,6-dideoxy-glucopyranose, mannose, cimarose,? ilose, lyose, ribose, digitalose, 4-amino-2,4,6- 26 á > tr ideso? i 1 i? ohexop irañosa, 4-amino-4, -d ideso? iglucop iranosa, 2, 3-d idesox i ramnop irapasa, 4-methox i-4, 6 dideox iramnop iranosa. An "oligosaccharide" is a sugar having 2- residues of monosaccharides, preferably 2-3. The last cnosaccharide residue of the oligosaccharide is known as the "terminal" oligosaccharide residue. The residue "monosaccharide" or "oligosaccharide" can be represented graphically in a ring or a chair configuration. For example, glucose (a moposaccharide) can therefore be represented: "ring" "chair" 27 * DETAILED DESCRIPTION OF THE INVENTION The present invention encompasses certain oxygen-substituted dextrose-containing 14 a / ninoesteraid compounds, method for their manufacture, pharmaceutical compositions thereof and a method of treating using said novel compounds and compositions thereof for the treatment of Failure. Cardiac Congestiv (CHF) in humans or other mammals. The compounds - specific and compositions to be used in the invention must, therefore, be pharmaceutically acceptable. As used herein, such a "pharmaceutically acceptable" component is one that is suitable for use in humans and / or other mammals without excessive adverse side effects (such as intoxication, irritation and allergic response), commensurate with a reasonable benefit ratio. /risk.

ACTIVE MATERIALS Compounds 14-amino steroids deoxy and substituted oxygenate containing sugar and the pharmaceutically acceptable acid or stere salts thereof of the general formula: (i) COORa, wherein Rs is a lower alkyl group of 1-6 carbon atoms; a lower alkyl group of 1-6 carbon atoms substituted by an amino group; an arylalkyl or heteroarylalkyl group or a carbocyclic ring, or (ii) CHR. &QH wherein R-. is a hydrogen atom or a lower alkyl group of 1-6 atoms • carbon, or (iii) COR '' ', where R' '' is hydrogen; lower alkyl of 1-6 carbon atoms; amino, lower alkyl of Cx ^ < i > replaced; amino or dialkylamino and b) Ras is -NRrR? wherein R7 and ß, which may be the same or different, are hydrogen atoms or lower alkyl group of 1-6 carbon atoms, and c) Ra is 29 (i) a deoxy or substituted oxygen monosaccharide residue, R12 they may be the same or different they are lower alkyl of 1-6 carbon atoms; hydrogen; hydroxy; fluorine; alkoxy; acetoxy; arylalkyl? i benzoxy; R is a lower alkyl of 1-6 carbon atoms; hydrogen; hydroxy; fluorine; benzoxy; arylalkyl; heteroarylalkyloxy; acetoxy or alkoxy; wherein also when Rs is a lower alkyl of 1-6 carbon atoms, ^, x or n can not be hydroxy or acetoxy; with the condition * additional that when RV? Í is hydrogen, Rio * is hydrogen, R ^ is hydrogen; hydroxy or acetoxy and R x is hydroxy, acetoxy or alkoxy, Rxo can not be hydroxy acetoxy; Laugh, be methyl; t can be a single double bond or (ii) a monosaccharide deoxy or oxigen-substituted residue. wherein Rn is oxyalkyl arylalkyl, heteroarylalkyloxy or lower alkyl of C? _? replaced, Ría. is methyl and d) R ^ is (i) OH or (i i) H, or (iii) 0 R a wherein R a is a mopasaccharide residue; acetoxy, benzoxy, arylalkyl, or heteroarylalkyl and e) S is (i) -CH- where a and b are simple bonds • o, (ii) = C where a or b is a double bond. The symbol "-" as used herein indicates that the stereochemistry is undefined and that the substituents in the steroid nucleus can be in the oc or ß configuration. The preferred stereochemistry is the β configuration at positions 3, 12, 14 and 17 in the steroid nucleus. Residues of monosaccharide deoxy or ogen 31 Substituted of the present invention can be linked to the 3-position in the steroid nucleus in the "s" -Adjusting configuration, someone skilled in the art of carbohydrate chemistry understands that the configuration of its listeners in a given sugar residue it is defined by the specific sugar named.

THE STEROID NUCLEUS The novel, sugar-deoxy or substituted oxygen-containing compounds 14- myosteroids of the present invention comprise a steroid nucleus wherein said steroid nucleus is variably substituted.

THE SUBSTITUENTS IN THE STEROID NUCLEUS The Substituents R-, • The Rx substituent is in position 17 in the steroid nucleus. There are three (3) possible substituents i- R ± can be COOR »where RB is hydrogen, a lower alkyl group of C? _? , a lower alkyl group of Ca? _, i, substituted by an amino group, or an arylalkyl or heteroarylalkyl group or a carbocyclic ring. Preferred substituents Rs are lower alkyl of C? _ ?, arylalkyl or a carbocycle. The preferred Rs is an alkyl 32 lower of C? _? and the most preferred Rs is methyl; thus, Rx is a carboxylic acid ester (COOCH3). Ri can also be CHR? OH where R¿. is a hydrogen atom or a lower alkyl group of Cj, _ ?; the preferred R ^ is H; thus, Rx is CH ^ OH. Finally, Rx can be COR '' ', where R' '' is hydrogen, lower alkyl, methylamino, amino or dialkylamino; the most preferred R '' 'is methylamine; thus, R x is CONHCH3. The most preferred substituent R is COORa wherein Ra is methyl and; thus, Rx is a methyl ester of carboxylic acid (see, CQOCH3). The Substitute R ~ - The substituent Rai is at position 14 in the steroid nucleus. There is a (i) substituent Ra. Ra is -NR7RβR-. and R? , which may be the same or different, are hydrogen atoms or lower alkyl group containing from 1 to 6 carbon atoms. Preferably R-. and R? they are H and thus, Ra is NHa.

The Substitutes R. * The substituent R3 is in position 3 in the steroid nucleus. There are two (2) substituents R3. R3 may be a substituted deso or substituted residue containing 33 sugar and that has the following structure: R 12 R ^ ?, R ^ ,, R o and Rl ?? which may be the same or different are lower alkyl of 1-6 carbon atoms; hydrogen; hydroxy; fluorine; alkoxy; acetoxy; Arylalkyloxy; heteroarylalkyl or benzoyl; R n is lower alkyl of 1-6 carbon atoms; hydrogen; hydroxy; fluorine; benzoxy; Arylalkyloxy; heteroarylalkyloxy; - acetoxy or alkoxy acid; wherein also when Rs is a lower alkyl of 1-6 carbon atoms, R ", RÍO or Rn can not be hydroxy or acetoxy; with the additional proviso that when R, ß is hydrogen, R or »is hydrogen, R ^ is hydrogen, hydro? i or aceto? and Rn is hydro? i, acetoxy alkoxy, Rio can not be hydroxy or acetoxy; Rxs¡ is methyl; acetoxymethyl or hydro? imetyl; t can be a simple or double link. Accordingly, in the compounds of the present 34 invention when Rx is COOR », Rs is a lower alkyl of 1-6 carbon atoms and COORs is a carbohydric acid ester, R«, and R ^ m and R10 # can be hydrogen but Rio or Rix can not be hydro ? io aceto? i; Rn can not be alkoxy. RIVER is selected from hydrogen, lower alkyl of 1-6 carbon atoms, fluorine, alkoxy, arylalkyloxy, heteroarylalkyl, or benzoxy. Rn is selected from hydrogen, lower alkyl of 1-6 carbon atoms, fluorine, arylalkyl, heteroarylalkyloxy or benzoxy. Thus, when R-9, R > ? »And io. they are hydrogen, Ri0 can be hydro? i and Rn is selected from lower alkyl of 1-6 carbon atoms, fluorine, hydrogen, arylalkyloxy, heteroarylalkyl? i or bepzo? i. In addition when R "*, R ^ and RÍO" are hydrogen, Ri0 can be acetoxy and Rn is selected from lower alkyl of 1-6 carbon atoms, fluorine, hydrogen, arylalkyl, heteroarylalkyl or benzoxy. Also, when R ^, R ^ m and R10ß are hydrogen, Rn can be hydroxy and Rio is selected from hydrogen, lower alkyl of 1-6 carbon atoms, fluorine, alkoxy, arylalkyloxy, heteroarylalkyloxy or benzoxy. When R ^,, R * - and RXO. they are hydrogen, Rn can be acetoxy and R or is selected from hydrogen, lower alkyl of 1-6 carbon atoms, fluorine, alkoxy, arylalkyl, heteroarylalkyloxy or benzoxy. Additionally, when Rx is COORs and Rs is a lower alkyl of 1-6 carbon atoms, and COORs an ester of carbohydric acid, R ^ can be hydro? i, R ^ m can be hydrogen, Ri0 can be hydrogen, but Rxo or Rx can not be hydroxy or aceto? i; and Rn can not be alco? i. Rio is selected from hydrogen, lower alkyl of 1-6-carbons, fluorine, alkoxy, arylalkyl, heteroarylalkyloxy or benzoy. Rn is selected from hydrogen, lower alkyl of 1-6-carbons, fluorine, arylalkyl, heteroarylalkyloxy or benzoy. So, when R *? is hydro? i, is hydrogen and R10? is hydrogen, R? it can be OH and Rn selects from hydrogen, lower alkyl of 1-6-carbons, fluorine, arylalkyl, heteroarylalkyl, or bepzoxy. In addition, when R ^ is hydroxy, R-m is hydrogen and Rt "is hydrogen, Rio can be acetoxy and Rn is selected from hydrogen, lower alkyl of 1-6-carbons, fluorine, arylalkyloxy, heteroarylalkyloxy or benzoxy. Also, when R < * is hydro? i, R- * is hydrogen and R? 0"is hydrogen, n can be hydro? i and Rio is selected from hydrogen, lower alkyl of 1-6-carbons, fluorine, alkoxy, arylalkyloxy, heteroarylalkyl or benzoxy When R «, is hydroxy, R-» «is hydrogen and R10ß is hydrogen, Rn can be aceto? I and RÍO is selected from hydrogen, lower alkyl of 1-6-carbons, fluorine, alco? I, arylalkyloxy, heteroarylalkyloxy or bepzoxi. In addition, when R is COOR », R-, it is a lower alkyl of 1-6 carbon atoms and COORB is an ester of 36 carboxylic acid, R., can be acetoxy, R ", ß can be hydrogen and R10ß can be hydrogen, but RI or Rn can not be hydroxy or acetoxy; and Rn can not be alco? i. Rxo is selected from hydrogen, lower alkyl of 1-6-carbons, fluorine, alkoxy, arylalkyloxy, heteroarylamyl lo? I or benzo? I. Rn is selected from hydrogen, lower alkyl of 1-6-carbons, fluorine, arylalkyl, heteroarylalkyl, or bepzoxy. So, when R ^ is acetoxy, R <;? is hydrogen and R "s" is hydrogen, RIO can be hydroxy and Rn is selected from lower alkyl of 1-6-carbons, fluorine, hydrogen, arylalkyloxy, heteroarylalkyl, or benzoy. In addition, when R ^, is aceto? I, R ^ is hydrogen and R or »hydrogen, R? S can be acetoxy and Rn is selected from lower alkyl of 1-6-carbons, fluorine, hydrogen, arylalkyloxy, heteroarylalkyloxy or benzo? i. Also, when R ^ is acetoxy, R- is hydrogen and Rxo »is hydrogen, Rn can be hydroxy and Rio is selected from lower alkyl of 1-6-carbons, fluorine, alkoxy, hydrogen, arylalkyl, heteroarylalkyl ? io benzo? i. In addition, when Rq.es aceto? I, R ^ is hydrogen and RÍO »is hydrogen, Rn can be acetoxy and Rio is selected from hydrogen, lower alkyl of 1-6-carbons, fluorine, alkoxy, arylalkyloxy, heteroarylalkyloxy or benzoxy The substituents R < * preferred are hydrogen, 37 fluorine, hydroxy, lower alkyl of 1-6-carbons or acetoxy. The substituents of R «? Particularly preferred are hydrogen, hydroxy and fluorine. Preferred R ^ substituents are hydrogen, fluorine, hydroxy and a lower alkyl of 1-6-carbons, preferably methyl and fluorine. Preferred Rio substituents are hydrogen, fluorine, hydroxy, arylalkyloxy, heteroarylalkyloxy or acetoxy or methyl. Particularly preferred Rx substituents are hydrogen, methyl and fluorine. Preferred Ri0 substituents are hydrogen, fluorine, hydroxy and a lower alkyl of 1-6-carbons, preferably methyl. Particularly preferred substituents are hydrogen, methyl and fluorine. Preferred Rn substituents are hydroxy, arylalkyloxy, heteroarylalkyloxy and acetoxy. Particularly preferred substituents Rn are hydroxy and acetoxy. Preferred R? A? Substituents are methyl, aceto? Imethyl, and hydroxymethyl. The R a substituent, particularly preferred is methyl. In a particularly preferred compound of the present invention, R ^? it is hydrogepo; R «is hydro? I; Rxo is hydrogen; RÍO »is hydrogen and Rn is hidro? I. Ra can also be a desoxy residue or substituted oxygen containing sugar and having the following structure: in dopde Rn is arylalkyl? i, heteroarylalkyl? or an oxosilane lower alkyl of 1-6 carbon atoms substituted and is methyl.

The Substituents R The substituent R ^ is at position 12 in the steroid nucleus. R? + Can be hydroxy (OH), hydrogen (H) or 0RA3, where R? A is a monosaccharide residue; acetoxy, benzoxy or arylalkyl or heteroarylalkyl. Preferred Rt + substituents are H or OR 3, where Ri 3 is a monosaccharide residue. Said monosaccharide residue is selected from hexose, 2-deoxyglucose, 6-deoxyheasose, 2,6-dideoxyhexose, ramosse, a glucose and arabinose, a digitous, a fructose, a galactose, ramnop iranosa, 39 hexopyranase, 6-deso? iglucase, 4, 6-dideso? ligneous, cimarous, xylose, lyosose, ribose, digitalosa glucosamine, 4-amino-2,4, 6-trideso? ilixohexopiranssa, 4 to ino-4, 6-dideso? iglucopyranose, 2,3-dideso? iramnop? ranosa 4-methoxy-4,6-dideoxyrampyranose, preferably the anomers ß-D or «-L thereof. The substituent R ^. particularly preferred is H. Z Z is -CH, where a and b are single bonds, = C, where a or b is a double bond. The preferred Z-C where a and b are simple links. The preferred 14-amino steroid compounds substituted deso? I or o? Substituted sugar-containing compounds of the present invention are: Acid methyl ester hydrochloride < 3β, 5β 14β, 17β) -14-amino-3-F. (2, 4-d i-O-acetyl-3, -d ideso? I-a-L manop i ranosi 1) or? i landrostapo-17-carbo? Ilic 40 Methyl ester of acid (3ß, 5ß, 14ß, 17ß) -14-a ino-3- (6-deso i-2,3-0- (1-met il-et i 1 iden) -4-0-Cl , 1-di met i let i 1) d imet i Isi 1 i 11- aL-manop i ranos i 1) o? i landrostane-17-carboxylic (3ß, 5ß, 14ß, 17ß) -14-amylo-3-C (6-deoxy-2, 3,4-tr iO-cet il - "- L-manop iranosi 1) ox i 1- hydrochloride N-methylantrostane-17-carbo? Ia? Da 41 Methyl ester of acid (3ß, 5ß, 14ß, 17ß) -14- ai no-C (2,4-di-O-ben zo i 1-3, 6-di desox i -aL-mapop ir nos i 1) ox i 1 androst ano-i 7-carbox í 1 ico Ethyl ester of (3ß, 5ß, 14ß, 17ß) -14-amino-C (2-0-benzayl-3,6-dideso? I - «- L-mannopyranosyl) or? I! 2 »androstane-17-carboxy 1 ICO ^ ^ (3ß, 5ß, 14ß, 17ß) -14-amino-3-C (6-deso? I- <xL-manop iranosi 1) ox i 3 -hydrochloride N-methyl landrostane-17-carbo? Iamide Methyl ester of acid (3ß, 5ß, 14ß, 17ß) -14- to ipo-3- (3,6-dideso? I-a-L-manop iranosi 1) or i 3 ndrostane-i 7- carbo? Lic 43 Methyl ester of acid (3ß, 5ß, 14ß, 17ß) -14 * amino- 3- CC4-0-benzoyl-6-deso? i-2,3- 0- (1-met ilet i liden) -a-L- manop iranosi 13ox i androst no-l 7-carbox l 1 ico Ethyl ester of (3ß, 5ß, 14ß, 17ß) -i4-amino-3- (4-0-benzoyl-6-deoxy-a-L-anopyranoside 1) oxy 3 androstane-17-carboxylic acid Methyl ester of acid (3ß, 5ß, 14ß, 17ß) -14 amino-3- (4-0-benzoi1-2,3,6-tridesoxy-β-L-mannopyranosyl) or γ 3 androst no-i 7- carbohydrate Methyl ester of acid (3β, 5β, 14β, 17β) -14 amypo-3- (2,3, -tridesoxy-β-L-mannopyran i i) oxy androstane-17-carbohydrate Methyl ester hydrochloride of (3ß, 5 14ß, 17ß) -14-amino-3- (3,6-dideoxy- "- L-mannopyranosyl) oxy androstane-17-carboxylic acid 1-methyl ester Methyl ester of acid (3ß, 5ß, 14ß, 17ß) -14 amino-3- (4-0-benzoyl-2,3,6-tridesoxy - «- L-mapopyranosi 1) oi 3 androstane-17-carbo? 1ico 46 Methyl ester of acid (3β, 5β, 14β, 17β) -1 amino-3- (4-0-benzoyl-3,6-dideoxy- "- L-mapopyranosyl) or 3-androstane-17-carbohydrate Acid (3ß, 5 14ß, 1ß) -14-amino-3- (2,3,6-russo? I-a-L-matro Iranosyl) methyl ester hydrochloride or anos-7-carbohydrate androsium hydrocarbons 47 Methyl ester of acid (3ß, 5ß, 14ß, 17ß) -14 to ino-3-C (4-0-benzoi1-, 3-didesh idro-2,3,6-rhipsoxy-aL-manopyranosine) oxy androstane-17 -carboxí lico 3 Methyl ester of (3ß, 5ß, 14ß, 17ß) -14-amino-3- (2,3,6-tr ideso? I-a-L-Iranosi-1) or i 3 ndros ano-17-carbo? Ilic Methyl ester of acid (3ß, 5ß, 14ß, 17ß) -14 amino-3- (2 ', 3', 6'-trideso? I-2 ', 2'-dif luoro-aL-flianop irano i 1) - or? i -androst ano-i 7-carboyl Ethyl ester of 3ß, 5ß, 14ß, 17ß) -14-amino-3- (6 '-deso? I-2' - et il-a-L-mannopyranosyl) -oxi 3-androstane-17-carbo? Ilic 49 Methyl ester of (3ß, 5ß, 14ß, 17ß) -14 amino-3-C (2 ', 6'-dideoxy-2', 2'-di luoro-a-L-mannopyranosyl) - axi3-androstane-i7 -carboxylic Acid methyl ester < 3β, 5β, 14β, 17β) -14 amino-3- (6'-deoxy-2'-C-met il-a-L-glucopyranosyl) -oxi-3-androstane-17-carboxylic acid Ethyl ester of (3ß, 5ß, 14ß, 17ß) -1 to ino-3-C ('-deoxy-3' -C-methy1-a-L-altropyranosyl) -oxi-androstane-17-carboxylic acid Methyl ester of acid (3ß, 5ß, 14ß, 17ß) -1 amino-3- (6'-dideoxy3 ', 3'-di-fluoro-aL-mannopyranosi 1) -o? I 3 androstane-17-carboxy 1 ico 51 Í4ß-amips-20β-methoxy-3β- (2 ', 3' -deso? I-4 '-aceto? I) • »A- (L) -ramnopiranosi 1-o? I 3-5ß.17a (H) pregnane Methyl ester of 14β-amino-3β-C (tri 2 ', 3', 4'-0-benzoyl) -a- (L) -myrnopyranosyiaxy 3-Sß-androstana-17β-carboarylic acid 52 Methyl ester of 14β-amipa-3β- (di-2 ', 3'-benzoyl-a- (L) -ramide-isosyl) -3, 5-androstane-17-carbohydrate Methyl ester of 14β-amylo-3ß-C (tetraacetyl i) -β- (D) -glucop Iranosi acid? i 3-5ß-androstane-17-carbo? ílic 53 Methyl ester of 14β-amine-3β-C (2 ', 3', 4 'tri-O-methyl -1) -a- (L) -myrnopyranosyl-1-oxy-5β-androst-17β-carboxylic acid Methyl ester of 14β-amino-3β- (3'-0-methyl) α- (L) -miranoyranosyloxy 3-5β-androstane-17β-carboxy li or 54 Methyl ester of 14β-amino-3β-C (di-2 ', 4'-Q-acetyl-3'O-met i 1) -a- (L) -ramnop iranosi loxi 3-5β-androstane-i 7ß- carboxylic Methyl ester of 14β-amine-3β-E (2'-0-met il) • a- (L) -ramnop i ranosi lox i 3-5β-androstapo-l 7β-carbaxyl li 55 14β-amino-3β-C (tri-2 ', 3', 4 '-O-acet i 1) - «- (D-rhamnopyran i lo? I -5β-androstane-l 7 (H) -carboxyiamide • A preferred starting material and / or intermediate for making the preferred compounds of the present invention is 2,4-O-dibenzoate of 3,6-d ideoxetholactone iL erythro-hexenone, which has the following structure: A preferred synthesis of said starting material / intermediate compound using the following general reaction scheme is described in Example 24 56 Part A. Generally, 2, 4-0-d acid 6-lactone ibenzoate 3-d ideso is synthesized. i-L-er i tro-he-2-enonic by first preparing the compound 2, 4-0-d ibenozoate of e-deoxy i-L-mannopyranosyl bromide, using the procedure described in Ness, R.K .; Fletcher, H.G.; Hudson, C.S. 3. Am. Chem. Soc. Vol. 73, p.296 (1951) and Allard, P; Dinh, T.H .; Boujette, C; Igolen, 3., 3. Med. Chem. 1961, vol 24, p. 1291. Then, said compound is added to DMSO and to a suitable base at temperatures of 50 ° C to 150 ° C, preferably of "60 ° C to 60 ° C, more preferably at 70 ° C for 5 minutes for about 30 minutes, preferably 15 minutes to about 20 minutes. Said suitable base may be chosen from tertiary amines, pyridine, collidine, amidine bases and heteroaryl amine bases (including, but not limited to pyridine and collidipa), preferably triethylamine (Et ^ N). While DMSO can be used only with the base, since it acts • as a solvent and as a reagent, it could only be used as a reagent (with an amount adjusted in accordance) and combined with a suitable solvent. Said suitable solvent includes chlorinated solvents, aromatic hydrocarbons, esters and ethers. After the reaction is complete, said reaction mixture can be poured into ice water, and then purified and extracted using method known to the inventors. e? pertas in the technique. While the preferred synthesis method for this starting material is defined in Example 24 given the general reaction described above, one skilled in the art could use various solvents, bases and purification extraction procedures to synthesize said starting material. Preferably the reaction is anhydrous. In addition to the general synthetic scheme described above and to the preferred synthesis encompassed by the scheme of Example 24, said preferred starting material 2,4-0 dibepzoate of 3,6-dideoxy-L-erythro-hex-2-a-lactone acid Enonic can also be synthesized using the general procedure set forth below; A preferred embodiment of the following general scheme is set forth in Example 25. Generally, a mannopyranose α-L-6-deoxy-mopohydrate is combined with a suitable solvent, including but not limited to DMF and acetopyryl. A suitable oxidant is then added including but not limited to bepzoyl peroxide, as shown, together with a suitable metal bromide chloride, selected from the group consisting, but not limited to, lithium bromide, lithium chloride, bromide nickel and nickel chloride. The resulting reaction mixture is stirred at temperatures of 20 ° C 100 ° C, preferably 20 ° C to 60 ° C, until the reaction is complete. A suitable bas selected from the group consisting of tertiary amines, amidine bases, and heteroarylamine bases (including, but not limited to, pyridine-calidin), preferably triethylamipate (Et 3 N) followed by the same is then added to the reaction mixture. addition of bepzoyl chloride. The resulting reaction mixture is stirred at 0 ° C to 100 ° C, preferably at 20 ° C 60 ° C, until the reaction is complete. Water is then added to the reaction mixture, and the product is extracted using methods available to those skilled in the art. Suitable solvents include, but are not limited to, aromatic hydrocarbons, steres and ethers. The extracts are purified and crystallized using method readily available to one skilled in the art. The preferred synthesis set forth in Example 2 can be varied by using different solvents, bases or promoters readily available to someone skilled in the art, using the geleral reaction procedure as described above. 59 MANUFACTURING METHODS The following non-limiting examples illustrate the manufacturing methods for the compounds of the present invention.

EXAMPLE 1 Synthesis of acid methyl ester (38. 58. 140- 178) -14-amino-3-r. (2 ', 3' .6'-trideoxy-4'-Q-benzoyl-1-L-raanopyranosyl) -oxi 3 -androstane-17-carboxylic acid Preparation of 6-deso? I-2,3-0- (1-met i let i 1idene) -LM methyl mannospyranoside-4-benzoate To a solution of 6-deoxy-2,3-0- (1-met) i lide > - «methyl mannospyranoside (6.0g, 27.5 mmol) in CHaCla! (50ml) 0 ° C under nitrogen is added dry pyridine (3 l) .Vas Evans, ME; Parrish, FW; Long, L. Carbohydr Res. 1967, 3 60 453, incorporated here for your reference. With agitation for 5 min, Benzoyl chloride (9.5 ml, 62.5 mmol) is added dropwise at 0 ° C. The reaction mixture is allowed to warm to room temperature for 30 min and is stirred at room temperature for 24 hours. The resulting solution is diluted with CHaCla. (lOOml), wash with Ha.0 and brine and dry. Evaporation produces a crude product that crystallizes from henion / ethyl acetate (3: 1) to provide 6-deso? i-2, 3-0- (i-met i let i liden) - methyl α-L-mannosanide-4-benzoate (6.1g, 76%) as a white solid.

Preparation of methyl 6-deoxy-'- L-mannopyranosid-4-benzoate HCl (aqueous) (3N, 3ml) is added to a solution of 6-deso? i-2, 3-0- (1-meti leti 1 iden) - «- L-mannopyranoside-4-benzoate methylo (6.1g, 16.9 mmol) in MeOH (190ml) at room temperature. The resulting mixture is stirred for 6 hours. Removal of the solvent produces a semi-solid residue that is crystallized from hexane / ethyl acetate. Recrystallization in the same solvent system produces methyl 6-deso? I-a-L-mannopyranoside 4-benzoate. (3.2g, 60.% ") as a white solid.An alternative reaction condition is as follows: P-TsOH (10 -i molar) is added to an aqueous methanolic solution of 6-deoxy-2,3-0- (1-methylethylidep) -a-L-anopyranoside methyl 4-benzoate. The resulting mixture is heated to 60 ° C for 12 hours. The evaporation of solvent produces a residue. The residue is disulted with CHasCl-a, washed with NaHCOa, (aqueous) 5 & , Ha.0, and brine and dry. The residue, after removal of the solvent, is crystallized from hexane / ethyl acetate to produce methyl 6-deo-i-a-L-mannopyranoside 4-bepzoate as a white solid.

Preparation of 2,3,6-tridesoxy-2,3-dehydromanopyran? Been 4 methyl benzoate A mixture of methyl 6-deo? -l-anopyranoside-4-benzoate (10g, 35.5 mmol), triphenylphosphine (39g, 149 mmol), triiodoimidazole (26.4, 26 mmol), imidazole (5.1 g, 75 mmol) and But + NI (12.5 g, 34 mmol) in toluene (650 ml) were stirred at reflux for 2 hours. The solution takes a red-brown color from the. produced. Toluene (150 ml) is added to the reaction mixture which is then poured into stirred aqueous NaHC0a (5.600 ml). The remaining residue is dissolved in acetone and poured into the aqueous phase. The resulting mixture is stirred for 5 minutes and separated. The organic layer is washed twice with aqueous NaaSa0a (5%, iOOml), twice with aqueous NaHC03 (5%, iOOml), twice in a row. with HaiQ (lOOml), and dried over anhydrous MgSO? +. The removal of the solvent leaves a crude product pale yellow. Purification by chromatography (co-elution / ethyl acetate in a gradient of 50: 1 to 50: 3.5) d a pure compound, 2,3,6-tridesoxy-2,3-dehydromanopyranoside methyl 4-benzoate ( 5.1, 56.%) with a colorless solid.

Preparation of methyl 6-deoxy-2,3-dideso-imanopyranoside-4-benzoate A suspended solution of methyl 2,3,6-trideso-i-2,3-dehydramanopyranoside-4-benzoate is shaken (3.2g, 12.9 mmol) and Raney nickel (excess, washed with Hß0 i-PrOH) in i-PrOH (120ml) under a hydrogen atmosphere (2612 kg / cma) for 6 hours. The resulting mixture is filtered and concentrated under reduced pressure to provide a colorless liquid product, 2,3,6-tridesoxanopyranoside-4-benzoate methyl (3.2g, 99%).

Preparation of 2,3,6-tr idesoxy-4-benzoi 1-1-chloro-β-L-Iranose BCI3 (1.0 M in CH 2 Cl 2, 20 ml) is added dropwise to a solution of 2.3.6. -trideoxyanopyranoside-4-benzoate d methyl (4.0g, 16.0 mmol) in CHaCl. (160ml) at -70 ° C magnetically shake. After the starting material (3 63 min), NaHCOa, aqueous (2%, 30ml) is poured into the mixture at low temperature (the aqueous is initially frozen). The separated organic layer is dried with Na 2 SO 4, filtered, then dried further with a 4A molecular sieve. This solution is used directly for the next reaction step. A small portion of the solution is evaporated in vacuo to give a pale yellow liquid product, 2,3,6,6-idesox i-4-benzoyl 1-1-loro-β-L-mannoprani. Preparation of (3β, 5β, 14β, 17β) -14 amino-3-C (2 '.3' .6 '-trides Q? I-4-benzoyl-aL-mannopyranosyl) -o? I -androstane- methyl ester 17-carboxylic acid As described in the US patent 4,665,260 incorporated herein by reference, to a magnetically stirred solution of aglycone, (3β, 5β 14β, 17β) -14-amino-3-hydro? I-androstane-17-carboalonic acid methyl ester (5.6g 16.0 mmol), molecular sieve of 4 & (iOg) and tetramethyl urea (3 mmol, 3.6 ml) in CHa, Cla (70 ml) under N at room temperature is added silver triflate (4.1 g, 16 mmol). The mixture is stirred for 10 min. before the compound 2,3,6-trideso? i-4-benzoyl-1-chloro-β-L-manopylaposa (4.0 g, 1 mmol) is introduced into a solution of CHa.Cla. (370 ml) The resulting mixture is stirred in the dark for 24 hours. After filtration, aqueous NaHCO3 (saturated 20 ml) is added to the filtrate. After stirring for 15 min, the organic fas is washed with aqueous aHCOa (5%), Ha, 0 and brine, s 64 • dry with N SO ^ and evaporate under reduced pressure to produce a residue. Purification by chromatography (silica gel, elution with CHCl-g / MeOH in a gradient d 500: 10 with 3 drops of NH.OH at 500: 50 with 15 drops of NH.alpha. OH) gives the product methyl ester of acid ( 3ß, 5ß, 14β, 17β) -14 amino-3-C (2 ', 3', '-trideso? I-4-benzoyl-a-L-mannopyranosyl) -oxi 3-androstapo-17-carboxylic acid and the This starting material is methyl (3ß, 5ß, 14ß, 17ß) -14-amino-3-hydroxy androstane-17-carboxylic acid. The glucoside s crystallizes from hexape / ethyl ether (10: 1) and recrystallizes from ethyl acetate / water to give the final white crystalline solid product.

EXAMPLE 2 Synthesis of Acid Methyl Ester (38. 58. 146. 178) -14-amino-3-C (2 * .3 / .6'-Rissoxy-benzoyl-6-butyranosyl) -oxi-3-androstane- 17- arboxiico • and 65 The combined mother liquor is concentrated from the preparation of (3β, 5β, 14β 17β) -14-amino-3-C (2 ', 3', '-tridesoxy-4-benzoyl-aL- methyl ester. mannopyranosyl) -oxi] -androstane-17-carbolic of Example i The final product (3β, 5β, 14β, 17ß) 14-a-ino-3-C (2 ', 3', 6'-) methyl ester trideoxy-4-benzoyl-β-L-mannopyran il-3-androstane-17-carboxylic acid is precipitated from hezh as an amorphous solid.

EXAMPLE 3 Synthesis of methyl ester of acid (38. 58. 148. 176> -14- awino-3-C (2 * .3 .6 -trideso i - «- -manopiranosi1) -oxi3- androstane-17-carboxylic acid NaOMe (300 mg, 5.6 mmol) is added to a stirred solution of methyl ester of acid (3ß, 5ß, 14β, 17β) -14 to ino-3- (2 ', 3', 6'-ri desox i -4 -benzo-il-aL-mannopyran il) - 66 oxy-3-androstane-i7-carboxylic acid (316 mg, 0.56 mmol) in anhydrous MeO (15 ml) at room temperature. The mixture was stirred for 12 hours under Na. Removal of the solvent under vacuum produces a white solid residue. This crude mixture is then divided between CHC13 and Ha0. The aqueous layer is extracted three times with CHCla. The combined extracts are washed with Ha0 and brine, dried and evaporated to give 210 mg of solid product. Purification by chromatography (silica gel, eluted with CHa.Clas / eOH / Ht OH in a gradient d 500: 20: 4 drops at 500: 40: 10 drops) gives the methyl ester d acid (3β, 5β, 14β, 17β) -14-amine-3-E (2 ', 3', 6'-trideso? IaL mannopyranosi 1) -oxi 3-andros non-17-carbohydrate pure as a white crystalline solid end product.

EXAMPLE 4 Synthesis of methyl ester of acid (38. 58. 148. 178> -14- to ino-3-C (2 * .3 ', 6 / - rudso i-8-L-mannopyranosyl) -oxi 3- androstane-1 - arboxilico 67 A mixture of (3β, 5β, 14β 17β) -14-amino-3- (2 ', 3', 6'-trideoxy-4-benzayl-β-L-mannopyranosyl) -oxi3-androstane-17-methyl acid ester Carboxylic (SOOmg, 0.6 mmol) and NaOMe (240 mg, 4.5 mmol) in anhydrous MeOH (15 mL) is stirred at room temperature under a. for 24 hours. Removal of the solvent produces a crude solid residue which is partitioned between CHClg, and Ha.0. The aqueous layer is extracted twice with CHC13. The combined extracts are washed with brine, dried and evaporated under vacuum to give the product. Purification by chromatography (eluyend with CHCla / MeOH / NH ^ OH) in a gradient of 500: 20: 5 drops 500: 30: 10 drops) gives the compound, methyl ester of acid (3β, 5β, 14β, 17β) - 14-amino-3-C (2 ', 3', 6 '-trideso? I-ß-L mannopyranosi1) -o? I 3-androstane-17-carboalkyl crystal izad as a white solid from ethyl ether and hexane.

EXAMPLE 5 Synthesis of acid methyl ester (38. 58. 148. 178) -14-amino-3- C6 'deoxy-2' .3 '- (1-methylethylidene) - / -benzoyl - «- L- ptanopiranosi13- oxi > -andros no-17- arboxi1ico Preparation of Acid methyl ester hydrochloride (38 58. 14ß. 17β) -14-amino-3-C (6'-deoxy-2 ', 3' - (l eti let i 1 iden) -aL-mannopyranosi 13-oxy> -androstane-17-carboxylic acid HCl etherate is added (catalytic amount) to a suspended solution of methyl ester hydrochloride of acid (3ß, 5ß, 14ß, 17ß) -14-amino-3- (6'-deaxi-aL-manopyrabinyl) oxy] -androstane-17-carboxylic acid , as described in US patent 4,665,260, incorporated herein by reference (12 g, 22.6 mmol) in 2,2-dimetho-propane (65 ml) dry DMF (60 ml) The mixture is stirred for 12 hours ambient temperature The solvent removal under vacuum 69 produces a light yellow residue which is crystallized from ethyl ether / hexane (11.2g, 92%) as a white solid, final product of methyl ester hydrochloride salt of acid (3β, 5β, 14β, 17β ) -14-amino-3-C. { 6'-deoxy-2 ', 3' - (1-met i let i 1 iden) -a-L-marano iranosil > -o? i -androstane-17-carbo? lico.

Preparation of (3β, 5β, 14β, 17β) -14-amino-3-αC (6'-deoxy-2 ', 3' - (1-met i let i 1 iden) -4'-benzoyl-1-methyl ester aL-anop iranosi 1 -ox i -androstane-7-carbo-yl To a stirred solution of (3ß, 5ß, 14ß, 17ß) -14-amino-3-C- methyl ester hydrochloride salt C6 '-desox i-2', 3 '- (1-met i let i 1 iden) -aL-manop iranosi 13-o? I 3-androstane-17-carbo-lico (6.3g, 14.5 mmol) in CHaCla Anhydrous (150 ml) is added dry pyridine (2.4 ml), benzoyl chloride (3.4 ml) and DMAP (177 mg, 1.4 mmol) at 0 ° C under Na.The mixture is allowed to warm to room temperature. 2 hours The reaction is complete in 3 days The evaporation of the solvent gives a crude product (10g) The purification by recrystallization from ethyl acetate / MeOH yields the HCl salt of the product The salt is dissolved in CHCl 3. and washed with aqueous NaHCOa (5%) and H ^ O and dried and evaporated to give the final product methyl ester of acid (3β, 5β, 14β, 17β ) -14- amipo-3-CC6 '-desox i-2', 3 '- (1-met i let i 1 iden) -4' benzoi 1-aL-manop iranosi 13-ox i -androstane-17-carbo ? í 1 ico. 70 • EXAMPLE 6 Synthesis of methyl ester of acid (38. 58. 148. 17ß) -14- awtino-3-C ('-deoxy-' -benzoi1 - «- -mano-piranosi1. -oxy-3-androstane-17 -carboxylic HCl etherate (saturated, 2.0 ml) is added to a suspended solution of (3β, 5β, 14β 17β) -14-amino-3-C-C6 '-deso? I -2', 3 '- (methyl ester) (3). 1-met i let i 1 iden) -4'-benzoi 1-aL-mannopyranosi 13-o? I > -androstane-l 7-carbo? 1 1 # (631 mg, 1.3 mmol) in MeOH (50 mL) at room temperature The solution becomes clear quickly. The reaction is complete after 1 hour. Evaporation of the solvent left a residue which was dissolved in CHaCl »(30ml) and mixed with NaHCOa (5%). The mixture is stirred for 15 min. The aqueous cap is brought with CHaClai. The combined organic layers are dried over a ^ SO ^. The removal of the solvent leaves a pure solid product, methyl ester of acid (3ß, 5ß, 14ß, 71 17β) -14-amino-3-C (6'-deso? I-4'-benzoyl-a-L-mannopyranosyl) -o? I 3-androstane-7-carboxylic acid.

EXAMPLE 7 Synthesis of acid methyl ester (38. 58. 148. 178) -14- ajB? Po-3- .. < 2 '.3'. & / - tridesoxy-4 / -Q-benzoyl-x-L-erythro-hex-2-enopyranosi1) -oxi 3-androstane-17-arboxylic and Preparation of methyl ester of acid (38. 5ß 14ß. 17ß) -14-amino-3-C (6'-deoxy-4'-benzoi 1-2 ', 3'-diphenium ionium - «- L-mannopyranosyl) -o? I 3-androstane-l 7 -carboxyl Phenyl chlorothiopoformate (0.41 ml, 3 mmol dropwise, under Nj. ta a solution of methyl ester d (3ß, 5ß, 14ß, 17ß) -14-amino-3-C (6'-) Deoxy-4'-benzoyl-a L-mannopyranosi 1) -oxy] -aprostane-17-carboxylic acid (720 mg, 1.1 mmol) and DMAP (560 mg, 4.6 mmol) in anhydrous CHaCN (15 mL) at 0 ° C. Let the mixture warm up to a temperature of 72 ambient. After 12 hours, the solvent is removed under vacuum. The residue is partitioned between aqueous CHa-Cla * and Hi + Cl The separated aqueous layer is extracted with CH.BCla. - The combined organic extracts are washed with NaHCO3 (5%), dried and evaporated to give a crude product. Purification by chromatography (eluting with CH2Cl3 / Me0H in a gradient of 500: 7 with 3 drops of NH2OH at 500: 20 with 10 drop of NH2OH) gives methyl ester of acid (3β, 5β, 14β, 17βX- 14 to ino-3-C ('-deoxy-4'-benzoi 1-2', 3 '-difen i 1 t ionoformyl-a-mannopyranosyl) -oxi-3-androstane-17-carboxylic acid (260 mg, another 92 mg they are obtained from a second purification of mother liquid, 36%).

Preparation of methyl ester of (3ß. 5β. 140. 178) -14 amino-3-C (2 ', 3', 6'-trideso? I-4'-Q-benzoyl- "- L-eri-1-methyl ester) he-2-eneryranosyl) -o? i 3-androstane-17-carbo-1-one AIBN (11 mg, 0.07 mmol) and n-Bu3SnH (25 mg, 0.96 mmol) were added to a solution of (3β, 5β, 14β, 17β) -14-amine-3 ~ C (6'-deso? I-4 ') methyl ester. -benzoyl-2 ', 3'-diphenylthiophen i 1-aL-manop iranosi1) -ox i 3-androstane-17-carboxylic acid (260 mg, 0.32 mmol) in toluene (30 ml). Solution s bubbles completely with a. for 10 min. The reaction mixture is then heated to reflux for 2 hours. The evaporation of the solvent leaves a residue that is purified by chromatography. Eluting with CHaCl ^ / MeOH in u 73 gradient of 400: 7 with 2 drops of NHi + OH at 400: 30 with 11 drops of NH ^ OH provides methyl ester of acid (3ß, 5ß, 14ßt 17ß 14-a ino-3- (2 ', 3', ' -trideso? -4'-0-benzoyl-aL-erythro-hex-2-enopyranosyl) -oxi-3-androstane-17-carboxylic acid as a crystalline sol.

EXAMPLE & Synthesis of acid methyl ester (38. 58. 148. 17B) -14- to "? Ipo-3-. { C6'-deoxy-2 / .3 / - (1-methylethylidene) -4 / -Q-t-butyIdimetiIsi1i1- < x-L-mannopyranosi -oxi > - carbonaceous-13-carrosilicate TBDMSiCl (2.2 g, 14.6 mmol) in DMF (IO) is added to a solution of (3β, 5β, 14β, 17β) methyl ester, 14-amino-3-CC6'-deso i-2 ', 3'- (1-met i let i 1 iden) -L-mannopyranosyl 3-oxy> -androstane-17-arboxylic (6.61 g, 12. mmol) and imidazole (1.7 g, 24.6 mmol) in anhydrous DMF (50 m under Na .. The mixture is stirred at room temperature for 74 hours. hours. If TLC (CH12Clffi / Me0H 10: 1.5) indicates that the reaction is incomplete, more TBDMSiCl (0.7g, 4.6 mmol) is added. After 14 hours, ice water is poured into the reaction mixture and the solution is poured four times with CH ^ Cla. (20 ml total). The extract is washed with H0, aqueous NaHC03 (2%) and brine, and dried over NaS0t + After which it is concentrated, this light yellow residue is crystallized from MeOH.The filtration gives acid methyl ester (3β, 5β 14β). , 17ß) -14-amino-3-CC6 '-deso? I-2', 3 '- (1-methylethylidene) -' 0-t-butylidimethyl Isi1i 1-aL-mannopyranosi13-o? I > androstane-l7-carboxylic acid as a white crystalline solid.

EXAMPLE 9 Synthesis of acid methyl ester (38. 58. 148. 178) -14-amino-3-C < 3 / .6'-dideoxy-2 '.4 / -O-dibenzoyl-«-L-mannopyranosyl) -oxi-3-n-drostane-17-arboxyl 75 • Preparation of methyl 6-deso? I - «- L-anopyranoside-2,4-0-dibenzoate See Yangm G-B-; Kong, F. Carbohydr. Res. 1991 211, 179. Kovac, P .; Edgar, J. 3. Qrq. Chem. 1992, 57.2455 incorporated herein for reference.

Preparation of 6-deso? i-3-0-phen i It iono-formyl-a-anopiranósido-2,4-0-dibenzoato methyl • Phenyl chlorothionoformate (54 ml, 0. mmol) is added to a solution of 2,4-0-benzoate of 6-deso-a-L-mapopyranoside (100 mg, 0.26 mmol) and DMAP (95 mg, 0.76 mmol in CH; anhydrous sCN (6 ml> 0 ° C under g, the solution is stirred at 0 ° C). for 1 hour and then at room temperature for hours, precipitation occurs during the reaction period The mixture is diluted with CH.Cla, (15 ml) and washed with H (aqueous) (0.5 N), Ha0, NaKC03 (aqueous ) (5%) and brine, and • dry. Evaporation of the solvent provides 6-deso? I -3-0 phenylthio-formyl-a-L-mannopyranoside, 2,4-0-dibenzoate d methyl which is used for the next reaction if additional purification. Further purification mediated chromatography (eluting with heel / ethyl acetate 10: 1) d a white solid. 76 Preparation of 3, 6-d ideso? i-L-manop iranoside-2.4-0 methyl dibenzoate AIBN (55 mg, 0.34 mmol) and n-Bu3SnH (2. ml, 13.4 mmol) are added to a solution of 6-deso i-3-0-phenyl ion. Methyl a-L-anopyranoside-2,4-O-dibenzoate. The solution is degassed by passing it through Na gas. last 20 min The reaction bottle is placed in an oil bath (120 ° C). After 1.5 hours, TLC indicates that the reaction is complete. The evaporation of the solvent leaves a residue. Purification by chromatography (eluting with hexapo / ethyl acetate) in a gradient of 500: 20 to 500: 50) leaves 3,6-dideoxy-α-L-mannopyranoside, 2,4-dibenzoate d methyl (1.6 g, 70 % in two steps from 2,4-0 benzoate of 6-deso iaL-manop iran been).

Preparation of (2S.3R .5S.6R) -2-chloro-3,5-0-dibenzoyl-6-methyla pirana BCl is added a (1.0 M in CH 1 C1X 1 6.5 ml) drop to a stirred solution 3,6-dideoxy-aL-mannopyranoside, methyl 2,4-0-dibenzoate (1.2g, 3.3 mmol) in CHaCla. (60 ml) at -76 ° C under nitrogen. After the starting material is completely consumed (30 min), aqueous NaHC03 (2%, 30ml) is poured into the mixture at a low temperature (the aqueous layer is initially frozen). The separated organic layer is dried with NafflS0t +, 17 it is filtered and dried further with a molecular sieve d 4A. This solution is used directly for the next step of the reaction. A small portion of the solution is evaporated under reduced pressure to provide a colorless liquid product, (2S, 3R, 5S, 6R) -2-chloro-3,5-dibenzoyl-6-methyl-pyran.

Preparation of (3β, 5β, 14β, 17β) -14 amino-3- (3 ',' -dideoxy-2 ', 4'-0-dibenzoyl-aL-mannopyranoyl) -oxy-3-androstane- methyl ester 17-carboxy 1 ico Silver triflate (1.0 g, 4.0 mmol) is added to a magnetically stirred solution of methyl ester d acid (3ß, 5ß, 14β, 17β) -14-amino-3-hydraxy-androstane-17-carboxylate. aglycone as described in the US patent No. 4,665,260, incorporated herein by reference (1.7 g 5.0 mmol), molecular sieve of 4A (3 g) and tetramethyl urea (6. mmol, 0.76 ml) in CHZela »(20 ml) under at room temperature. The mixture is stirred continuously for 1 min before introducing a solution of (2S, 3R-5S, 6R) -2-chloro-3,5-0-dibenzoyl-6-methyl pyran (1.2 g, 3.3 mmol) and CHaiCla »(160 ml). The resulting mixture is stirred in the dark for 19 hours. After filtration, add aqueous NaHC03 (saturated, 20 ml) to the filtrate. After stirring for 15 min, the organic phase is washed with aqueous NaHCO (2%), Ha.0 and brine, dried with NSO 2 and evaporated under vacuum to provide a residue. This crude mixture dissolves in CHaiClg. The majority of the remaining methyl acid (3β, 5β, 14β, 17β) -14-amino-3-hydroxy-1-androstane-17 carboxylic ester crystallizes out of the solution. The product is further purified by chromatography (silica gel, elution with CHa, Cla. / MeOH in a gradient d 500: 10 with 3 drops of NHl + 0H at 500: 20 with 6 drops of N +0 to give acid methyl ester). (3β, 5β, 14β, 17β) -14-amino-3-C (3 ', 6'-dideoxy-2', 4'-0-dibenzoyl-aL-manno-iranosi-1) -oxi3 androstane-17-carbo-ion , which is recrystallized from hexane / ethyl acetate (10: 1) as a white solid.

EXAMPLE I Synthesis of methyl ester of acid (38. 58. 148. 178) -14- amipo-3-C (3 '.' -didesoxy - «- L-mannopyranosyl) -oxi 3-androstane-17-carboxylic acid NaOMe (4.0 g, 73.6 mmol) is added to a solution 79 agitated from (3β, 5β, 14β, 17β) -14 amino-3- (3 ', 6'-dideoxy-2', 4'-0-dibenzoyl-α-L-mannopyranosyl) -glycosane-androstane ~ acid methyl ester i7-carboxylic acid (6.2 g, 9. mmol in anhydrous MeOH (40 ml) at room temperature The mixture is stirred for 24 hours under Na ~ The removal of solvent under reduced pressure leaves a solid residue. in CHC13 and Ha0 The aqueous layer is extracted with CHC13 three times The combined extracts are washed with brine, dried and evaporated to leave a solid product The purification by chromatography (silica gel, eluted with CHa? Cla./ MeOH / NHt + OH in a gradient d 500: 10: 3 drops at 500: 40: 12 drops) provides methylic acid ester (3ß, 5ß, 14ß, 17ß) -14-amino-3- (3 ', 6'-dideso? IaL manopiraposil) - or? and 3-androstans-17-pure carbohydrate as a white crystal. EXAMPLE 11 Synthesis of Acid Methyl Ester (38. 58. 148. 178) -14-amino-3-C (3 '.6'-dideoxy-2 * -0-benzoyl-1-L-mannopyranosyl) -oxi 3 -androstane-17-carboxy 1 ico 60 The cramatographic separation of the crude mixture obtained in Example 10, methyl ester of (3ß, 5 14ß, 17ß) -14 ~ amino-3- (3 ', 6'-dideso? IaL-mano iranosyl) oxy 3- ndrostane-17-carboxylic acid also leaves a polar product, methyl ester of (3ß, 5ß, 14ß, 17ß) -14-amino-3 C (3 ',' -dideoxy-2 '-0-benzoyl-aL- mannopyranosyl) -oxi 3-androstane-17-carboxy 1 ico.

EXAMPLE 12 Synthesis of hydrochloride, of methyl ester of acid (38. 58. 148. 178) -14-amino-3-C (3 #, 6'-dideoxy-2 '.4-Q-di cetyl-«-L - mannopyranosyl) -oxi 3-androstane-17-carboxylic acid Methyl ester of (3ß, 5β, 14β 17β) -14-α-ino-3- (3 ', 6'-dideoxy-α-l-uransyranosyl) -oxi-3-androstane-17-carboxylic acid ester (640 g, 1.75 g) is suspended. mmol) in MeOH (iOml at -5 ° C.) Methanolic HCl is added dropwise and the solid enters solution.The stirring is continued for 10 min.

The solution is evaporated at 0 ° C to provide a solid white salt of methyl ester hydrochloride of (3β, 5β, 14 17β) -i 4-α-ino-3-C (3 ', 6'-didesoαl-mannopyranosyl) hydrochloride. ) -o? i 3-androstane-17-carboxylic acid (quantitative yield). This salt is subsequently dissolved in a solvent acetic anhydride / CHASCl-j, (1: 1) (30 ml) and add drops of dry pyridine. The mixture is stirred at a low ambient temperature for 46 hours. After concentration, the residue is precipitated from hexane / EtsjQ to leave methyl ester hydrochloride acid (3ß, 5ß, 14ß, 17ß) -14-amycto-3-C (3 ', 6'-dideso i-2' , 4'-diacetyl-aL-mannopyranosyl) -o? I 3-androstane-i7-carbo? Lyl as a white crystal.

EXAMPLE 13 Synthesis of hydrochloride of (38. 58. 146. 176) -14-amino-3-C ('-deoxy- < x-L-mannopyranosi1) -oxy-3-n-drostane-17-methyl-amide 62 A hydrochloride solution of (3β, 5β, 14β, 17β) -14-amino-3-C (6'-deso? I aL-mannopyranosyl) -o? I3-androstane-17-carbo is added. Ilic, as described in the US patent 4,665,260, incorporated herein by reference (500 mg, 0.94 mmol) in MeOH (10 L) to a steel pump and cooled to -5 ° C. Methylamine is bubbled into the solution until the volume increases by 1 ml. The pump is sealed and placed inside a 125 ° oven for 3 days. After the pump cools to -10 ° C the seal is opened and the solution is transferred to a flask and evaporated under vacuum to leave a solid. Recrystallization of this crude product in MeOH / ethyl acetate yields hydrochloride of (3ß, 5ß, 14β, 17β) -14-αn-3-C (6'-diisolalycopyranosyl 1) -o? I -androstane- i 7-met i lick (quantitative performance) as a crystalline solid. • 63 EXAMPLE 14 Synthesis of hydrochloride of (38. 58. 148. 178) -14-amino-3-Z < £ > '-deoxy-2 .3' .4"-O-triacetyl -« - L-mannopyranosyl) -oxi 3-androstane-17-methylamide A solution of (3β, 5 14β, 17β) -14-amino-3- (6'-diso-iaL-mannopyranosyl) -α-androstane-17-methylamide hydrochloride (1.25 g, 2.35 mmol), pyridine s ( 0.5ml) and acetic anhydride (20ml) at ambient temperature low a. for 3 days. The evaporation of the solvent b vacuum leaves a semi-solid residue. Solid precipitates are formed with the addition of ethyl acetate. The solid obtained from filtration is recrystallized from ethyl acetate and MeOH (10: 0.5) to provide (3ß, 14β, 17β) -14-amino-3- (6'-deox i-2 ', 3' hydrochloride. .4'-tr iaceti 1-a anop iranosi 1) -o? i -androstano-i 7-met i lami da com a crystalline white sol. 64 EXAMPLE 15 148-amylo-38-C (tri-2 / .3 *, 4 ^ -O-methyl-3-6-androstane-178-carboxylic acid methyl ester) 1.0 g of methyl ester of 14-azido-3β-Ca- (L) -ramnopyranosyloxy 3-5β-andrast non-17β-carboxylic acid, obtained as described in the patent E.U.A. 4,665,260, incorporated herein for reference, b an argon atmosphere, in 20 ml of dimethylformamide b agitation in an iron bath. 250mg of • suspension of sodium hydride (60% in oil) and 1 ml of methyl iodide, and the reaction is continued under stirring at 0 ° C for 5 hours. The reaction mixture is neutralized with acetic acid, washed with 60 ml of sodium bicarbonate, extracted with ethyl acetate and then washed with water and saturated NaCl solution. After purification by column chromatography on silica gel and eluted 65 with a mixture of chloroform-ethyl alcohol (99: 1), you obtain the methyl ester of 14β-azide-3ß- (t 2 ', 3', 4'-0-met i 1) -a- (L) - rhenopranosyl lo? i 3-5ß-apdrostane-17 carbo. The azido group is converted to an ami group after the addition of the above azido derivative (640 in a solution of methyl alcohol (60 ml) of hydrazine hydr and the addition of Pd (0H) 3 as a catalyst (mg). The reaction mixture is heated under reflux for 1 hour, after filtration on Celite, extraction with ethyl acetate, washing with water and with a saturated solution of NaCl, the residue is purified by evaporation chromatography, eluted with a heptane- ethyl acetate-triethylamine (49: 49: 2) to give 14- amino-3ß-C acid methyl ester (r i-2 ', 3', 4 '-Q-met i 1) -a- (L) - ramnop i ranosi lox i 3-5ß-androstane-17β-carboyl. 66 EXAMPLE 16 Acid methyl ester 148-amino-38-C (3 # -0-methyl) - «- < D-Rhamnopyranosyloxy 3-58-androstane-178-arboxyl This compound is prepared as described in Example 15 but using 360 mg of methyl ester of 14β-azido-3β- (3'-0-met il) -a- (L) -amnopyranosyl i-5β-androstane- methyl ester. 17β-carboxylic acid instead of 14β-axido-3ß-E methyl ester (tri-2 ', 3', 4'-0-methyl 1) -a- (rampop iranosi lo? I -5ß-androstapo-l7ß-carbo • Methyl ester of 14β-amino-3β-C (3'-eti 1) -a- (L) -ramnop iranosi loxi 3-5ß-andros ano-l 7β-carboalionic acid is obtained. 67 EXAMPLE 17 148-α-NON-36-C (tri-2 '. 4'-di-Q-acetyl 3'-Q-methy1) - "- (L) -myrnopyranosyloxy 3-58-androstane-l78 acid methyl ester - carboxyl The methyl ester of 14β-azid 3β-C (3'-0-methyl) -a- (L) -ramnopyranasyl) and 3-5ß-apdrostane-17β-carboxylic acid (370 mg) is dissolved, which is used in the Example 16 in 5 methylene chloride and to this solution are added 0. pyridine, 0.2 ml acetic anhydride and then 2.5 mg dimethyl amino pyridine. The mixture is stirred for 4 hours at room temperature and a part of the solvent is removed by heating. 10 ml of ammonia are poured from the solution, the residue is brought with ethyl acetate, then washed with water and saturated NaCl solution. After CLAP chromatography, methyl 4-azido-C (2 ', 4'-di-0-acetyl-3'-0-met i a- (L) -ramnopyranosiloxy 3-5β-androstane- is obtained. 7β-carboxylic acid. 66 Methyl ester of 14β-amino-3β-C (2 ', 4'-di-0-acetyl-O-met i1) -a- (L) -miranoyranosyl and 3-5ßn-androstane-17β-carboxylic acid is obtained from the above 14-az derivative by the same procedure as in Axis 16.

EXAMPLE 16 148-α-NON-38- (tri-2 '.3', 4 / -0- benzoy 1) - "- (L) -myrnopyranosyloxy 3-58-androstane-178- acid methyl ester 13 g of 14-azido-3β-hydro? I-5β-androstane-17β-carboalonic acid methyl ester and 6.3 ml tetramethyl urea are placed in a three-neck flask equipped with a magnetic stirrer, containing approximately 200 ml of ethylene chloride The mixture is stirred under a nitrogen atmosphere, a molecular sieve (15g, 4A) is added and the mixture is left under stirring for 1 hour. 12.6 g 69 are added zinc trifluoro methane sulfonate and then g of tri-O-benzayl-rhamnosyl bromide are dissolved in 300 ml of methylene chloride dropwise. The reaction is continued overnight under agitation at room temperature. After the addition of a saturated solution of sodium bicarbonate, filtration is carried out, washing with methylene chloride, washing with water and then with a saturated NaCl solution, extraction with methylene chloride and drying, crystallization in methyl alcohol is obtained methyl ester of 14β-azido-3β- (tri-2 ', 3', 4'-benzoi 1) -a- (L) -ramnop iranosi lox i 3-5β-androst non-17 # -carbohydric acid . The above 14-azido derivative is refluxed with sodium tellurium borohydride for two hours under argon. The reaction mixture is allowed to cool to room temperature and 270 mg of the above 14-azido ester are added in a 2 ml solution of deoxygenated absolute alcohol. The mixture is kept under stirring for 2 hours and then for 15 minutes in air so that excess reagent is removed. After filtration on Celite, elution with a mixture of chloroform-alcohol ethyl (90:10), the filtrate is evaporated until it is dried. The bases are diluted with toluene and extracted with an aqueous solution of 2% sulfamic acid. After the addition of carbonate 90 sodium and methylene chloride extraction, 169 mg of base and 42 mg of neutral compound were obtained. Sodium chloride is added to saturation and the polar compound is obtained, which is also present the first basic extract. The compound is purified on a column of silica gel to obtain the methyl ester 14β-amino-3β- (tri-2 ', 3', 4'-0-benzoyl) - "- (rhamnopyranosyl)? -androstane-17ß-carboxylic.

EXAMPLE 19 Methyl ester of 148-amino-38-C (tri-2'-Q-met il) - "- (D-rhamnopyranosi loxi 3-58- ndros ano-178- arboxylic acid 200 mg of methyl ester of 14β-azido-3β-C (3'-0-benzoyl-2'-methy1) -a- (L) -ramnop iranosi it are reacted overnight. i 3-5ß-androstane-l 7ß-carbo? Ilic and 0.2 ml of sodium etapolate in a mixture of 10 ml of methyl alcohol and 10 ml of methylene chloride ba 91 argon, while agitation is carried out under ambient temperature. After extraction with methylene chloride with water and with saturated NaCl solution, the residue is purified by chromatography, eluting with a methylene-acetone chloride mixture (65:15) followed by crystallization in a mixture of methyl alcohol-isopropyl alcohol . 115 mg of the methyl ester of 14-azido-3β-C (2'-0-met il) -a- (L) -ramnop iranosi loxi-3-5β-apdrostane-17β-carboxylic acid ester obtained as above are treated with hydrazine hydrate in the presence of catalyst according to the method of Example 15, and it obtains 14β-amino-3β-C (2'-0-met il) (L) -ramnop iranosi lox i-5β-androstane methyl ester -17ß ~ carboxíli o.

EXAMPLE 20 Methyl ester of 14β-amino-3α-C (tetra-O-acetyl) -β- (D-glucopyranosyloxy-58-androstane-178-carboxylic acid) 92 Dissolve 1.5 g of methyl ester of acid 14 • amino-3β-hydro? I-5β-androethane-17β-carbohydrate, 0.65 g tetramethyl urea, 1.5 g of molecular sieve (4A) in 25 ml methylene chloride, under argon, in an ice bath. The mixture is stirred and 1.63 g of zinc trifluoro-sulphonate are introduced, and 5 g of tetra-0-benzoii-a- (D) -glucosyl bromide dissolved in 22 ml of ethylene chloride are slowly added in 1 hour. Then, 0.6 g trifluoromethal zinc sulfonate is added and the temperature is increased • to room temperature, after 2 hours, 0.2 g of silver trifluoromethyl sulfonate is added. The reaction is continued overnight and 0.5 g silver trifluoromethyl sulfonate is added twice at d hour intervals. When the reaction is complete, 30 ml of saturated sodium bicarbonate solution is added to the reaction mixture and the insoluble is removed by filtration.

# Rinsing with ethylene chloride. The filtrate is washed with sodium bicarbonate, water and then with a saturated NaCl solution. Extraction is carried out with methylene chloride and the residue is filtered on silica (Merck 6 eluting with a mixture of methylene chloride-methyl alcohol (99: 1), and then with a methylene chloride-methylene alcohol mixture. -ammonium (95: 5: 0.5) G is obtained from an oily product The previous product is treated c 93 sodium methanolate to produce the corresponding glucopyranosyl derivative which is acetylated dimethylaminopyridine and acetic anhydride in methylene chloride at room temperature for approximately hours and is reduced on the 2 'position by Pd / C. obtains 14β-amino-3ß- (tetr acet i1) -β- (D) -glucopyranosyl methyl ester? i -5ß-androst no-i 7β-carboxylic acid. EXAMPLE 21 148-α-Inno-38- (tri-2 '.3', 47-Q-benzoy1) -a- (L) -aminopyranosyl-3-yl-3-androstane-178-carboxylic acid methyl ester A 2M trimethylaluminum solution (7.7 ml) in 25 ml of toluene is slowly added to a suspension of 0.6 g of ammonium chloride in 20 ml of chloroform a -1. The reaction mixture is cooled to ambient temperature with stirring for 2 hours and prepare a solution 94 contains 0.6 g of 14β-azido-3β- (L) -rampopyranosiloxy-5β-androstane-17β-carboxylic acid methyl ester as described in the U.S. Pat. 4,655,260, incorporated for reference. This reaction mixture is dissolved in a 25 ml mixture of toluene and 5 ml chloroform are added thereto. The reaction mixture was heated under relf for 6 hours, then at 40 ° C for 16 hours. The mixture is poured into 20 ml of 2.5N hydrochloric acid in an ice bath, neutralized with ammonia. After evaporation, the residue is filtered and purified by chromatography, eluting with a mixture of methylene hydrochloric acid methylene hydroxide (90: 10: 1). After the filtration, 0.54 g of 14β-azido-3β-Ca- (L) -m-p-pynopyranosyl and 3-androstane-17β-carboalic acid amide are collected (yield: 70%). 0.5 g of the amide of 14-azido are dissolved in 30 of chloroform and 0.5 ml of acetic anhydride and 55 of dimethylaminopyridine are added therein. The reaction mixture is stirred for 15 hours at ambient temperature. After extraction with methylene chloride, the organic phases are washed with water (the pH is adjusted to approximately 3 add hydrochloric acid), then with saturated aqueous N solution and dried over sodium sulfate. In this way it obtains the corresponding tri-0-acetyl derivative 95 (yield: 100%). The above derivative (0.5 g) is dissolved in 60 ml methanol under argon, and 0.5 g of ammonium formate followed by 0.25 g of Pd / C (10%) are added. The reaction mixture is heated under reflux for 30 minutes and Celite filtered. After evaporation to dryness, they collect 0.5 g of crude product, which is purified by chromatography on a column of silica gel, eluting with a mixture of methylene chloride-methyl alcohol-ammonium hydroxide (65: 15: 1.5 ) to give the final amide product of 14β-amino-3β- (tri-2 ', 3', 4'-0-acetyl) -1L) -amnopyranosyl loxy-5β-androstane-17β-carboxylic acid.

EXAMPLE 22 148-amino-208-methoxy-38 (2 * .3 '-deoxy-4' -Q-aceti1) - «- (L) rhamnopyranosiloxy 3-58.17« (H) -preqnano 96 223 mg of di-3,4-0-acet-il- (L) -ramnal are dissolved in i ml of dry chloroform, and a solution containing 760 mg of 14β-azido-20β-meta-3β- is added thereto. hydro? 5β, 17a (H) -pregnane and 0.09 ml of BF3 / EtOa in 2.6 ml of methylene chloride. The reaction is carried out at room temperature for 25 minutes and then the reaction mixture is placed on crushed ice. After extraction with methylene chloride, washing with sodium bicarbonate, the residue is purified by chromatography on a column of silica gel under reduced pressure, eluting with an ethyl acetate-hexane mixture (1:12) and 321 mg of 14-azide-20β-meto? I-3β- (2 ', 3'-dehydro-2', 3'-deoxy-4 '-0-acet i 1) - «- (L) -miranopyranosiloxy3-5ß , 17a (H) -pregnano. The above 14-azido derivative is dissolved in 4 ml of absolute ethanol and a hydrogenation reaction is carried out in the presence of 100 mg of PtOa »as catalysed for 24 hours. After evaporating to dryness, filtering is subjected to silica gel column chromatography, obtain the final product, 14β-amino-20β-meto? I-3β-C (2 ', 3 deoxy-4'-0 -acet il) -a- (L) -amnopyranosiloxy 3-5β, 17"(H) -pregnano, which crystallizes in the henian. 97 EXAMPLE 23 148-Amino-3? -C (di-2 .3-o-benzoyl) - () -aminopiranosyloxy-3-58-androstane-178-carboxylic acid methyl ester 1.5 g of 14-amino-3β-hydro? I-5β-androstapo-17β-arbo-organic acid methyl ester are dissolved, as described in the patent of E.U.A. 4,665,260 incorporated for reference, 0.65 ml of tetra et ilurea and 1.1 g molecular sieves (4A) in 20 ml of methylene chloride. The mixture is stirred and 1.05 g of zinc trifluoromethyl sulfonate are introduced in 30 minutes. Then, 2.4 g of di-2,3-0-benzoyl-a- (rhamnosyl bromide dissolved in 15 ml of methylene chloride was slowly added to the reaction mixture for 4 hours after extraction with methylene chloride. with water (in the presence of ammonia) and the sec on sodium sulfate and evaporation to dryness, obtain 3.2 g of a yellow oily residue.

The oily residue is subjected to silica gel column chromatography, eluting with a mixture of methylene chloride-methylene alcohol-ammonium hydroxide (96: 2: to give the final product 14β-am 3β- methyl ester) ( d i-2 ', 3' -0-benzoi 1) -a- (L) -ramnop iranosi loxi 3-5β-androstane-17β-carboxylic acid as a white powder.

EXAMPLE 24 Synthesis of 14-amino-3-C (3'-d'-dideoxy-2 ', 4 * -Q-dibepzoyl) - «- L-mannopyranosyl) oxy 3-androstane-17-carboxylic acid methyl ester Methyl ester of 14-amino-3-C (3 ', dideso? I-2', 4'-0-dibenzayl) -aL-manop iranosi l) oi 3-androstane-17-carbo? Lyl ester (prepared as described in Example 9 of the present invention) can also be synthesized according to the procedures described below: Preparation of 2.4-0-dibenzoate of 3-dideoxy-L-er -lactone-itro-hez-2-enonic acid Deoxy-α-L-mannopyranosyl 2,3,4-tri-O-benzoate bromide is added, anhydrous (727.2 g, 1.35 m [prepared as described in Ness, RK, Fletcher, H. Hudson, CS, 3. Am Chem. Societv. 1951, Vol. 73, pp. 296 in Allard, P., Dinh, TH; Gouyette, C; Igolen, 3; .M Chem. 1961, Vol. 24, p.1291) to a mud heated (70 ° C) DMSO (3.6 L) and Et ^ M (451 ml), 3.24 mol) with vigorous agitation. The reaction mixture is stirred at this temperature until the reaction is complete (15-20 min) as indicated by thin layer chromatography. The reaction mixture is then poured into ice water (4.3L). The product is extracted with EtOAc (4.3 L) and the extracts combined with water (2 x 4.3L) and then with saturated solution of N (3L). The organic layer is dried over MgSO 4, activated carbon is treated, filtered through Celite and evaporated to give a yellow solid. The yellow solid 100 crystallize from isopropanol (150 ml) to give white crystalline product. The mother liquor is optionally concentrated to give a second crop of product.

Preparation of 2.4-0-dideo-arabino-hexonic acid 2.4-0-dibenzoate It is used 3,6-dideoxy-L-erythro-hex-2-enonic acid o-lactone 2,4-O-dibenzoate to make 3,4-dideoxy-3-e-lactone dibenzoate -axon hexon The procedure used is that described by Várela, O.J.; Cirelli, A.F.; From Lederkremer, R. Carbohvdrate Research. 1979, Vol. 70, p.27, with the idea that acetone is used as a solvent instead of EtOAc. To a solution of 2,4-dibenzoate of e-lactana 3,6-dideso? I-erythro-he? -2-enonic, (166.6 g, 0.46 mol) acetone (1.0L) is added Pd / C 10% (1.7 g). This mixture then shakes under a hydrogen atmosphere (2612 kg / c PARR apparatus) at room temperature for 16 hours. The reaction mixture is then filtered through Celite and 101 The filtrate is concentrated under reduced pressure to give white crystalline solid.

Preparation of 2,4-0-dibenzoate of 3,6-dideoxy-a.β ar bino-he? O iranosa A solution of Li (BuO) g-H (120.7 g, 0.47 mol) in THF (672 ml) is added slowly (1 hour) to a cooled solution (-10 ° C to -5 ° C) of 2,4- 6-Lactone-3,6-dideoxy-L-arabino-heonic acid 6-lactone dibenzoate (166 g, 0.47 mol) THF (1.6 L) while the temperature is maintained below 0 ° C. The reaction is complete after stirring for additional hour (s) and checked by thin layer chromatography. The reaction mixture is quenched with saturated NaHCO 3 solution (600 ml) to which Celite (g) is added. After filtering on a Celite bed and rinsing with additional THF, the organic phase is separated, saturated NaHCO3 solution is washed (2? ID, dried over MgSO.t. + concentrated under reduced pressure to give the product. 102 product is purified after the dissolution EtOAc / heptane 25% and making the silica gel slurry. then filter the silica gel, rinse EtOAc / heptane 25% and the filtrate is concentrated to give product as a clear oil or foam.

Preparation of 2, 4-di-0-benzoate-1- (2,2-trichloroethanimidate) from 3,6-dideso? I-a-L-arabino-he? Opirano 2,4-Di-0-benzoate-1- (2,2, trichloroethanimidate) of 3,6-dideoxy? I-a-L-arabino-he? Opyran is prepared according to the general procedure as described by Urban, F.3.; Moore, B.S., Breitenbach, R. Tetrahed Letters. 1990, Vol. 31, p.4421. Add CsaC03 (5.6 g, 15.9 mmol) trichloroacetonitrile (155.5 mL, 1.55 mol) to a solution of 2,4-di-0-benzoate of 3,6-dideoxy-α, β-L-arabino-hexopyran (136.0 g, 0.39 mol) in CHaCla, (1.0 L). After agi 103 for 5.5 hours at room temperature, the reaction mixture is washed with water, saturated NaCl solution, added over MgSO.sub.3, concentrated under reduced pressure and azeotropically distilled with toluene to give the product as a foam.

Preparation of methyl ester of acid (38. 5ß, 14β. 17β) -amino-3-C (3 ', 6'-dideoxy-2,4'-dien-ibenzoyl) -aL-ftianopyranosyl) -oxi 3- androstano-l 7-carbo? lico Nolecular sieves (4A, 5g) are added to (3ß, 5β, 14β, 17β) -amino-3-hydro? I-androstane-17-carboalic acid methyl ester solution (5.0 g, 14.3 mm [prepared as it is described in US Pat. No. 4,664,260, incorporated herein for reference) and trimethyl-silsilyl triflate (3.67 ml, 20.0 mmol) in CHaCl '(200 ml) and stirred for 2 hours at -25 ° C to -15 ° C. A solution of 2,4-di-0-benzoate-1- (2,2-trichloroethanimidate) of 3 ', 6'-dideso-iaL-arabi 104 is added slowly. he? opiranssa (6.17 g, 16.4 mmol) in CH ^ Cla. (60 ml) for hours while maintaining the temperature within -25 ° C to -15 ° C. The reaction mixture is ag for 16 hours. (If thin-layer chromatography indicates that the reaction is incomplete, more trifl of trimethylsilyl and 2,4-di-0-benzoate-1- (2,2-trichloroethanimidate) of 3 ', 6'-di-loxy-aL may be added. ARABIO-IANOUS AEROSY The reaction mixture is washed with saturated NaHCOO solution (250 ml), the aqueous layer is extracted again with CH-aCla »-2 x iOOml) and the combined layers of CHai are washed with water. (300 ml) and then with saturated NaCl solution < 300ml). The CH-BCIS layer is dried over MgSOn. and concentrated under reduced pressure to give the crude product.

EXAMPLE 25 Synthesis of 2,4-Q-dibenzoate of β-lactone of 3,6-d i esoxy-L-erythro-hex -enone acid The 2,4-0-dibenzoate of S-lactone acid 3, 105 dideoxy-L-erythro-hex-2-enonic [prepared as described in __ Example 24 of the present invention3 can also be prepared according to the procedures described below: α-6-deoxy-mannopyranos monohydrate ( 10 g, 54.9 mmol) to DMF or acetonitrile (100-200 m followed by the addition of benzoyl peroxide (1.0 to equivalents) and a suitable metal chloride or bromide (0. 1.5 equivalents), such as lithium bromide, chloride • Lithium, nickel bromide, nickel chloride, etc. The reaction mixture is stirred at 20 ° C to 100 ° C until complete, as indicated using c-thin chromatography. A suitable base, such co-triethylamine (6.0 to 10.0 equivalents) is then added, followed by the addition of benzoyl chloride (3.0 to 5.0 equivalents). Let this be shaken at an interval of 20 ° C to 60 ° C until • complete, as indicated, using thin-layer chromatography. Water is then added to the reaction mixture and the product is brought with a suitable solvent, such as EtO. The combined organic extracts are washed with water, dried over NaS0t + and concentrated to give the crude product. This is then crystallized from EtOH for the pure product as a white solid. 106 EXAMPLE 26 Synthesis of Acid Methyl Ester (38. 58. 148. 17B) -14-amino-3-C (3,6 / -dideoxy-2 '. 4 / -Q-dibenzoyl) - «- L-anopyranosi1) -oxi 3- ndrostane-17- arboxiol The methyl ester of (3β, 5β, 14β, 17β) -1 amino-3-C (3 ', 6'-dideoxy-2', 4'-0-dibenzoyl) -aL-mannopyranosyl) -oxi 3-androstane C-prepared carboxylic acid is described in Example 9 and Example 24 in the present invention! it can also be synthesized according to procedures described below: Molecular sieves (4A, 0.5 g) are added to a solution of methanesulfonic anhydride (0.326 g, 1.66 mmol) CHajCla (lOml) and stirred for 0.5 hours at 0 ° C. Then triethylamine (0.4 ml, 2.7 mmol) and 2,4-di-0-benzo (0.611 g, 1.72 mmol) [prepared according to the test described in Example 243 and continued hard stirring are added. minutes. (See procedure as generally described in Leroux, 3; Perlin, A.S., Carbohydr Research (1976) 67, 163, except that triethylm is used in place of s-collidine). Methanesulfonic acid (Ol 1.54 mmol) is then added, followed by the addition of α (3β, 5β, 14β, 17β) -14-amino-3-hydroxy-androstane-carboalic acid methyl ester (0.5 g, 1.43 g. mmol) Prepared as described in the US patent 4,665,260 incorporated herein for reference]. The reaction mixture is allowed to warm to room temperature and is then stirred for hours. The reaction mixture is filtered over Celite, washed with water (10 ml) and with saturated NaCl solution (10 ml). The layer is filtered and evaporated to give the crude product, methyl ester acid maleate (3ß, 5β, 14β, 17β) ~ 14-amino-3 - [(3 ',' -dideso? anopyranosyl) -oxi 3- androst no-17-carbo? unique EXAMPLE 27 Synthesis of methyl ester of acid (38. 58. 148. 176) -14 amino-3-C (3,6'-dideoxy - "- L-mannopyranosyl) -oxi-androstan-1-arboxylic acid The methyl ester of (3β, 5β, 14β, 17β) -1 amino-3-C (3 ', 6'-dideoxy-2', 4'-0-dibenzoyl) -aL-mannopyranoeyl) -oxi-androstane- The C-prepared 7-carboxylic acid described in Example 10 in the present invention can also be synthesized according to the procedure described below: To a solution of (3ß, 5 14ß, 17ß) -14 -amino-3-C (3 ', 6' -dideso? i-2 ', 4' -0-dibenzoyl) -a-mannopyranosyl) -o? i3-androstane-l 7-carbo? l (200 g, 0 mmal) Cprepared as described in Example 26 in the present invention! in a mixture of MeOH (2L) and CH ^ Cl- ^ (NaOMe (16 g, 0.30 mol) is added with stirring. room temperature. The reaction mixture is allowed to stir for 24 hours and then it is quenched by adding NaHCO 3 (54 g, 0.65 mol). This is stirred for 2 hours, filtered and concentrated under reduced pressure to give an oily residue. The residue is slurried in Heptane / 10% t-butyl methyl ether (2.25 L) for 2 hours, filtered and re-made in water (ID for 2 hours, product is obtained as a white solid after which The residue is filtered and dried.

EXAMPLE 26 Synthesis of acid methyl ester maleate (36. 58. 14 178) -14- mino-3-C (3 '.6'-dideoxy- "- L-mannopyranosyl) -oxy-3-androstane-17-carboxylic acid The solution of methyl ester of acid (3ß, 5 14ß, i7ß) -14-amino-3-C (3 ', 6'-dideso? I-2', '-0-dibenzoi 1) -a manopyranosyl) - oxi 3-androstane-7-carboxylic acid (15.og, 3 110 mmol) [prepared as described in Example 27 of the present invention] in MeOH (50 ml) is added dropwise maleic acid solution (4.0 g, 34.5 mmol) in methanol. then add acetone (200ml) and the mixture is cooled to 24 hours. The white crystalline product then filters and dries.

DETERMINATION OF PHARMACOLOGICAL ACTIVITY It is postulated that the positive inotropic effect of cardiotonic steroid compound is due to its effect on pump a *, K * in the sarcole of cardiac muscle cells. Specifically, cardiotonium steroids inhibit Na *, * activated adenosine triphosphatase, which in turn leads to an increase in intracellular calcium. Thus, more calcium is available to activate the contractile mechanism. See, generally, Goodman and Gilman, Pharmacoloqical Basis of Therapeutics. Chapter 34 (6th 1990). The positive inotropic activity of a new chemical entity is determined in cardiac tissues and whole animal models. Isolated tissue provides direct measurement of the inotropic potency of a compound while the system is virtually free of metabolic, neurahormonal, and absorptive 111 which can influence the response of the tissue. The tests in viVQ provide a determination that takes into account those physiological parameters that are not found in the isolated tissue test. In the trial for inotropic activity, papillary heart strips are used from cobay heart. Although the papillary muscle is more involved with valvular function, the basic contractile response that is muscle is similar to that of the ventricular muscle. , a dissected segment of papillary muscle is suspended from the heart of a guinea pig in an organ bath which provides the tissue with an aqueous environment that contains the substrates necessary for cellular function at a controlled temperature. By fixing a free end force transducer of the muscle strip such that the muscle is suspended between a fixed base and the transducer and applying an electrical stimulus, it is possible to measure shrinkage or shrinkage in response to various compound test concentrations. Under typical conditions, inotrop positive is defined as the increase in contractile force produced by an unknown agent and the data is usually reported as the concentration of drug necessary to produce a 50% increase in contractile force from the baseline (ECso). The determination of positive inotropy in vivo 112 does two ways. The first is very similar to the measurement described for the in vivo method in which the stress meter is sutured outside the heart to determine contractile force. In the second record, force transducer is inserted into the left ventricle to detect pressure changes. The contractile force of myocardium correlates with the rate of development of pressure within the left ventricle and is expressed as c + dP / dt. In any case, the data is reported as the amount of drug necessary to achieve an activity level of 30% increase in contractility or + dP / dt (for example, EDao) and is expressed as mg of drug / weight of the animal.

PHARMACEUTICAL COMPOSITIONS The novel substituted sugar containing 14-amino steroid and oxidant compounds of the present invention can be administered to humans or other mammals by a variety of routes, including, but limited to, oral dosage forms and injection (intravenous, intramuscular, intraperitoneal and subcutaneous One skilled in the art can formulate other numbers of dosage forms containing the novel substituted sulfur-free 14-ami steroids steroids q 113 contain sugar of the present invention, using suitable pharmaceutical excipients as def post later. Considering pleasing the patient, they generally prefer oral dosage forms. The term "pharmaceutical composition" as used herein means a combination comprising a safe and effective amount of the active ingredient, compue 14-amino steroid deoxy or novel substituted oxygen contains sugar, or mixtures thereof, and pharmaceutically acceptable excipients. The phrase "safe and effective amount," as used herein, means a large amount of a compound or composition that positively modifi es significantly the symptoms condition to be treated, but small enough to avoid serious side effects (in a proarc reason of benefit / risk), within the scope of the solid medical judgment. The safe and effective amount of active ingredient for use in the pharmaceutical compositions used in the method of the present invention will vary with the particular condition to be treated, the age and physical condition of the patient to be treated, the severity of the condition, duration of the treatment, the nature of the concurrent tera, the particular active ingredient that is being used, the pharmaceutically acceptable excipients 114 particular that are being used and similar factors within the knowledge and experience of the head physician. The term "pharmaceutically acceptable excipients" as used herein, includes any physiologically inert, pharmacologically inactive mate known to one skilled in the art, which is compatible with the physical and chemical characteristics of the particular act ingredient, the 14-amyloid steroid deso compound. iu substituted sugar containing sugar, selected for use u Pharmaceutically acceptable excipients include, but are not limited to, polymers, resins, plasticizer fillers, binders, lubricants, polishing disintegrants, solvents, co-solvents, quenching systems, surfactants, preservative agents sweeteners, flavoring agents, dyes, pharmaceutical grade pigments and viscosity agents. The term "oral dosage forms" as used herein, means any composition that is administered to an individual by providing said gastrointestinal tract composition of an individual, via the mouth of the individual. For purposes of the present invention, the supplied form can be found as a tablet, covered or uncovered; solution; suspension; or a capsule with cover or without cover. 115 The term "injection" as used herein means any pharmaceutical composition that is systematically administered to a human or mammal or animal by providing a solution or emulsion that conti the active ingredient by making a sting on said individual's skin, in order to supply said emulsion solution. in the circulatory system of the individual already by intravenous injection, intramuscul intraperitoneal or subcutaneous. One skilled in the art can satisfactorily control the rate of systematic delivery by manipulating any one or more of the following: (a) the appropriate active ingredient; (b) the pharmaceutically acceptable excipients are acceptable as long as the variants do not interfere with the activity of the particular active ingredient selected; (c) the type of the excipient, and the concomitant desirable permeability thickness (swelling properties) of said excipients; (d) conditions dependent on the time of the excipient itself and / or within the excipients; (e) the particle size of the granulated active ingredient; (f) the pH dependent conditions of the cipients. 116 As discussed above, pharmaceutically acceptable excipients include, but are not imitated, resins, fillers, binders, lubricants, solvent brighteners, disintegrants, co-solvents, surfactants, preservatives, sweetening agents, agent flavorings, buffer systems, pharmaceutical grade pigment dyes and viscosity agents. The preferred solvent is water. Flavoring agents that are among those useful for the present include those described in Reminqton's Pharmaceutical Sciences, 16th edition, M Publishing Company, 1990, p. 1266-1300, incorporated here for your reference. Suitable pharmaceutical compositions for use in the present invention generally contain 0.2% flavoring agents. The dyes or pigments found herein useful for the present include those described Handbook of Pharmaceutical E? Cipients, pp, 61-90, 1966 by American Pharmaceutical Association & amp;; the Pharmaceutic Society of Great Britain, incorporated herein by reference. Pharmaceutical compositions in the present invention generally contain 0.2% dyes or pigments. Preferred co-solvents include, but are not limited to, ethanol, glycerin, propylene glycol, polyethyl glycols. The pharmaceutical compositions of the present 117 invention include 0-50% co-solvents. Preferred buffer systems include, but are not limited to, acetic, carbonic, phosphoric, succinic, maleic, tartaric, citric acetic, benzoic, lactic, glyceric, gluconic, glutaric glutaric acids and their sodium, potassium and ammonium salts. Those who particularly prefer are phosphoric, tartaric, citric and acetic acids and their salts. The pharmaceutical compositions of the present invention include 0-5% buffer systems. Surfactants include, but are not limited to, polyoxyethylene glycol fatty acid esters, monoalkyl polyoxyethylene ethers, sucrose monoesters, lanolin ethers and ethers, alkyl sulfate salts and sodium, potassium and ammonium salts of fatty acids. . The pharmaceutical compositions of the present invention include 0-2% surfactants. Preferred preservatives include, but are not limited to, phenol, alkyl esters of parahydrobenzoic acid, o-fephenphenol, benzoic acid and salts thereof, boric acid and salts thereof, sorbic acid and salts thereof, clearbutanol, alcohol benzyl ti erosal, phenylmercuric acetate and nitrate, nitromerso benzalkonium chloride, cetyl iridinium chloride, met paraben and propylparaben. The salts of benzoic acid, cetylpyridine ethylparaben chloride and propylparaben are particularly preferred. The pharmaceutical compositions of the present invention include 0-2% preservatives. Preferred sweeteners include, but are not limited to, sucrose, glucose, saccharin, sorbitol, mannitol aspartame. Particularly preferred are sucrose and saccharides. The pharmaceutical compositions of the present invention include from 0-5% sweeteners. Preferred viscosity agents include, but are not limited to, methylcellulose, sodium carboxymethylcellulose, hydro? Ipropylmethylcellulose, sodium hydropropylcellulose alginate, carbomer, povidone, acacia gum, guar g, urano gum, and tragacanth. Particular preference is given to methylcellulose, carbomer, xantha gum, guar gum, povidane, sodium carboxymethylcellulose and magnesium aluminum silicate. The compositions of the present invention include 0-5% viscosity agents. Preferred fillers include, but are not limited to, lactose, mannitol, sorbitol, tribasic calcium phosphate, calcium dibasic phosphate, sugar compressible starch, calcium sulfate, dextrocellulose and microcrystalline cellulose. The compositions of the present invention include from 0-75% fillers. Preferred lubricants include, but not 119 limit to, magnesium stearate, stearic acid and ta • The pharmaceutical compositions of the present invention include 0.5-2% lubricants. Preferred brighteners include, but are not limited to, talc and colloidal silicon dioxide. Pharmaceutical compositions of the present invention include i-5% brighteners. Preferred disintegrators include, but are not limited to, starch, starch glycolate, crospovidone starch, sodium elose and microcrystalline cellulose. The compositions of the present invention include 4-15% disintegrants. Preferred binders include, but are not limited to, acacia gum, tragacanth, hydro? Ipropylcellul pregelatized starch, gelatin, povid hydropropylcellulose, hydroxypropylmethylcellulosemethocellulose, sugar solutions, such as saccharoses. * sorbitol and ethylcellulose. The compositions of the present invention include 1-10% binders. The compounds of the present invention can comprise from 0.1% to 99.9% by weight of the pharmaceutical compositions of the present invention. Preferably compositions of the present invention comprise approximately 20% to approximately 60% by weight of pharmaceutical compositions of the present invention. 120 • Accordingly, the pharmaceutical compositions of the present invention include 15-95% of an active ingredient, 14-amino substituted steroid deso or substituted? -group containing sugar, or a mixture thereof; 0 of ageptes flavorings; 0-50% co-solvents; 0-5% damping system; 0.2% surfactants; 2% of conservatives; 0-5% sweeteners; 0-5% viscosity agents; 0-75% fillers; 0.5-2% lubricants; 5% rinse aid; 4-15% of disintegrators and 1-10% • binders. Suitable pharmaceutical compositions describe in the present invention. The variation of the non-limiting examples described in the present invention is completely within the capabilities of one skilled in the art to achieve a wide range of pharmaceutical compositions. The selection of a pharmaceutically acceptable carrier to be used in conjunction with the sugar-substituted substituted amino-substituted steroid compounds of the present invention is basically determined in the manner in which the compound is to be administered. If copolymer is to be injected, the preferred pharmaceutical carrier is sterile physiological saline, whose pH is adjusted to about 7.4. The pharmaceutically acceptable vehicles suitable for the application 121 Topical include those suitable for use in crem gels, tapes and the like. The preferred mode of administration of the sugar-containing substitute 14-amino-substituted steroid steroids of the present invention is orally. The preferred form of dosage unit is therefore tablets, capsules and the like, which comprise safe and Effectiveness of the 14-am substituted sulfur-containing substituted sulfur-containing steroids of the present invention. Pharmaceutical vehicles acceptable for the preparation of unit dosage forms for oral administration are well known in the art. Their selection will depend on secondary considerations such as taste, cost and storage stability, which are not critical for purposes of the present invention and which a person of ordinary skill in the art can do without difficulty. Various dosage forms can be used including solid forms such as tablets, capsules granules and bulk powders. These oral dosage forms comprise a safe and effective amount preferably of O.img to 5.0 mg of the 14-amine substituted steroid desoxygen containing sugar. preferably, these oral dosage forms buy 0.25-1.0 mg of the 14-amino steroid deso? i or o? replaced that contains sugar. The tablets can be tablets, crushed tablets, coated with sugar coated, coated with film or mult co primidae, containing binders, lubricant diluents, disintegrating agents, colorant agents, flavoring agents, flow inducing agents and suitable melting agent. Liquid or dosage forms include aqueous solutions, emulsion suspensions, solutions and / or suspensions reconstituted from non-effervescent granules and effervescent preparations reconstituted from effervescent gr nul containing solvents, preservatives, emulsifying agents, suspending agents, diluent sweeteners, ageptes of fusion, coloring agents and agent flavoring suitable. Preferred vehicles for oral administration include gelatin, propylene glyc cottonseed oil and sesame oil. The compositions of the present invention may also be administered topically to a subject, for example by directly placing or smearing the composition on epidermal or epithelial tissue of the subject. Such compositions include, for example, lotions, cream solutions, gels and solids. These topical compositions comprise a safe and effective amount, preferably 0.5 mg to 2.0 mg of the 14-amino steroid deoxy or oxygen. replaced that contains sugar. More preferably, topical compositions comprise 1.0 mg of 14-am steroid deoxy or substituted oxygen containing sugar. Suitable vehicles for topical administration preferably remain on the skin as a continuous film, and resist removal by transpiration or immersion in water. Generally, the carrier is organic in nature and is capable of dispersing or disbating therefrom the 14-amino steroid deoxygen or substitute sugar-containing steroid. The vehicle may include emollient emulsifiers, thickeners and pharmaceutically acceptable solvents. The compositions of the present invention can also be administered via the inhalation route. The compositions are prepared in a matrix comprising solvent such as water or a glycol., preservatives such as methyl or propyl paraben and propellants such as nitrogen dioxide. Additionally, the compositions of the present invention can be administered via a subcutaneous implant formed from silicone elastomers of ethylene vinyl acetate copolymers or lactic acid glycol co-polymers. In order to illustrate how to prepare pharmaceutical compositions containing novel co- 124 present invention, the following limiting examples of pharmaceutical compositions are presented.

EXAMPLES OF PHARMACEUTICAL COMPOSITION EXAMPLE 1 An immediate release dosage form (tablet) containing the methyl ester hydrochloride (3ß, 5ß, 14ß, 17ß) -14-amino-3- [(2,4-di-O-acetyl-3, dideoxy) -aL-manop iranasi 1) -oxi 3-androstane-17-carbo? í 1 ico.

Active ingredient Amount of 1.0 mg hydrochloride methyl ester of acid (3ß, 5ß, 14ß, i7ß) -14-amino-3- [(2,4-di-0-acetyl-3,6-d idesoxy-aL-mannopyranosyl ) -oxi 3-androstane-17-carbolic Excipients Microcrystalline cellulose 26.5 mg Lactose, hydrated 67.2 mg Crospovidone 3.0 mg Magnesium stearate 0.3 mg 125 • Manufacturing Instructions: (for 10,000 tablets) 1) 10.0 g of the drug, 265.0 g of microcrystalline cellulose, 672.0 g of lactose and 30.0 g of crospovidone are mixed in a Patterson-Kelley mixer (PK) or an appropriate mixer. 2) The above mixture is mixed with 3.0 g of magnesium stearate in a PK mixer or an appropriate one. 3) The final mixture is compacted into tablets F 100.0 mg in a suitable tableting machine.

EXAMPLE 2 A parenteral dosage form containing (3β, 5β, 14β, 17β) -14-amino-3- [(6-deox-2,3,4-tri-0-acetyl-α-L-mannopyranosyl) -o? Hydrochloride. i 3-N-methylandrostane 17-carboxyamide and suitable for use as an injection * intravenous (I.V.) has the following composition: Inactive Active Amount hydrochloride 1.0 mg (3ß, 5ß, 14ß, 17ß) -14-amino-3- [(6-deoxy-2,3,4-tri-0-ce i 1-aL-anus iranosi 1) - oxy-3-N-methylantrostane-17-carboxy ida 126 Excipients Mannitol 200.0 mg Citric acid / sodium citrate enough quantity to adjust the p between 5.5 - 6.5 Manufacturing Instructions (for 1000 small bottles) 1) Dissolve 1.0 g of the drug, 200.0 g mannitol and sodium citrate and sufficient citric acid 2200.0 ml of sterile deionized water for injection, 2) The above solution is filtered through a sterile membrane filter of O.22 microns. 3) 2.2 ml of the previous solution is placed inside small glass jars. Type Desupés is lyophilized in a suitable lyophilizer. 4) After lyophilization, the small flasks are covered with bromobutyl or other suitable stoppers are sealed. The lyophilized product is reconstituted with ml of sterile water for immediate injection prior to use. 127 • EXAMPLE 3 An oral sustained release dosage form (tablet) containing the methyl ester of aci (3β, 5β, 14β, 17β) -14-amino-3 - [(3,6-dideoxy-iarylopyranosyl) -a? 3-Androstane-17-carboxylic has following composition: t Active ingredient Amount methyl ester of acid 5.0 mg (3ß, 5ß, 14ß, 17ß) - 14-amino-3- [(3,6-d idesoxy-a-L-mapopyranosi 1) -a? i - androstane-17 -carboxylic Excipients Hydroxypropylmethylcellulose 120.0 mg Lactose, hydrated 120.0 mg Magnesium stearate 12.0 mg Colloidal silicon dioxide 4.0 mg Manufacturing Instructions (for 10 000 tablets) 1) 50.0 g of the drug, 1. kg of hydroxypropylmethylcellulose and 1.2 kg of lactose are intimately mixed in a double-vessel Patterson-Kelley mixer or a suitable mixture. 2) To the above mixture is added 120 g of agnesium stearate and 40 g of colloidal silicon dioxide, this is mixed lightly in a suitable mixer. 3) The above mixture is compacted into tablets weighing 261.0 mg in a suitable tablet press.

MISCELLANEOUS EXAMPLES In addition to the three previous examples, the active ingredient drug is formulated in a number of different dosage forms: 1) a pharmaceutical aerosol containing solven (for example water, glycols), preservatives (methyl or pra paraben) and propellants (nitrogen, carbon dioxide) other suitable excipients. 2) a rectal suppository containing theobroma oil or polyethylene glycols, 3) a subcutaneous implant containing silicone elastomer, copolymers of ethylene acetate vipi copolymers of ico-glycolic acid and hydrogels and other suitable polymers, 4) implantable devices available 129 # commercially, *. 5) a transdermal system containing silicone fluid in an ethylene vinyl acetate copolymer membrane or other suitable ingredients for delivery c or without the aid of iontophoresis. 6) a ucoadhesive buccal patch containing hydrocolloid polymers (hydroxyethylcellulose hydroxypropylcellulose, povidone) and other suitable polymers METHODS OF TREATMENT The term, Cardiac Failure Congestive "CHF" as used here, denotes a progressive disease in which hemodynamic capacity as well as heart structure is increasingly and irreversibly compromised. New York Heart Association (NYHA) has classified progression of CHF according to the patient's symptoms four functional classes.

Functional Classification of the New York Heart Association Class I. Patients with C3.rd i s.aa disease but if limitations resulting from physical activity. 130 Ordinary physical activity does not cause excessive fatigue, dyspnea, or angina pain. II. Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable when they are at rest. The ordinary activity results in fatigue, palpitation, dyspnea or angina pain. III. Patients with heart disease that result in a marked limitation of physical activity. He is comfortable when they are at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, angina pain. IV. Patients with heart disease that results in the inability to carry out any physical activity without discomfort. Symptoms of heart failure or angina syndrome may be present at rest. If any physical activity is carried out, the discomfort increases. NYHA classes III and IV, also referred to as evident congestive heart failure, are often treated by administering compounds that increase the contractile cardiac function by exerting a positive inotropic effect. Reference compound to increase the cardiac contractili is oral digoxin. The treatment of the symptoms of CHF evident by administering inotropes to increase 131 CO and satisfy the metabolic needs of the body can improve the quality of life of a CHF patient since the heart can supply the metabolic need of the body. Conventional wisdom, however, indicates that inotropic, such as digitalis, can increase the t mortality since the inotropic action creates an extra work ca for the heart. Moreover, digita has a low proportion of therapeutic doses: technical and administration of digitalis in a class prior to III the classification of NYHA may not be prudent. Additionally, the inotrope of bipyridine Milrinone has been shown to aggravate ventricular arrhythmias possibly increasing mortality. See DiBianco, et al., "A Comparison of Oral Milrinone, Digoxin and Th Combination in the Treatment of Patients with Chronic He Failure," N. In l. 3. Med. 320: 677 (1969) The term "he odinamic" as used here refers to the mechanical capacity of the heart. The initial hemodynamic consequence of heart failure is a decrease in the volume of the plunger stroke which is a measure of the amount of blood expelled with each beat of the heart. The heart then compensates to increase the CO and maintain the flow to the vital organs. As cardiac failure worsens, intracardiac pressures rise, as do pulmonary and venous pressures. The heart is 132 increasingly unable to provide the required CO. The term "structural damage" as used herein refers to microscopic and macroscopic changes in the heart of a person suffering from CHF. The following changes take place structurally at a microscopic level: the first state of cardiac hypertrophy is morphologically characterized by increases in the size of the fibrobrils and mitochondria as well as the lengthening of the mitochondria and nuclei. The muscle cells are longer than normal, but cellular organization is conserved greatly. In a state of more advanced hypertrophy, preference increases in the size or number of specific organelles, such as the mitochondria, as well as the irregular addition of new contractile elements in localized cell areas, result in subtle abnormalities of the organization and cell contour The adjacent cells may vary in their degree of elongation. Cells subject to long-term hypertrophy, show more obvious disruptions in the cellular organization, such as nuclei scratched between elongated highly lobed membranes, which displace adjacent myofibrils and cause disturbance of the normal register of Z-bands. The preferential increase temp the mitochondria are supplanted by a predominance in 133 • volume of myofibrils. The late state of hypertrophy is characterized by cell death and loss of the contractile elements with marked disruption of Z bands, severe disruption of the arrangement normally paral of the sarcomeres, dilatation and increased tortuosity of the T tubules, and replacement of the contractile elements with fibrous tissue. . See Braunwald, Heart Disease: A Textb of Cardiovascular Medicine. Vol, 1, (3rd ed 1966). It's microscopic changes are revealed at a macroscopic level • by cardiac hypertrophy or heart lengthening. The hypertrophic heart becomes less efficient due to microscopic changes that cause loss of contractile elements and fibrotic deposition, and clinical symptoms of the patient worsen as it progresses through each functional classification of NYHA. The compounds of the present invention increase cardiac contractility. The dosing interval can be between .01 mg and 5 mg per day as determined by the attending physician according to the mode of administration of the severity of CHF and the duration of treatment. In order to illustrate the particular utility of these unique 14-amino substituted deso? I or o? Ig sugar-containing steroid compounds for the treatment of CHF, the following limiting clinical examples are presented. 134 CLINICAL EXAMPLES EXAMPLE 1 A 65-year-old white obese woman with a history of non-insulin-dependent diabetes mellitus and a myocardial infarction 2 years earlier is admitted to the coronary care unit 12 hours after she presents symptoms with acute myocardial infarction. hospital stay is complicated by an acute pulmonary edema that is manifested by severe dyspnea in orthopnea repose, distension of the jugular vein, bilateral rattle towards the middle scapula; a dilated heart bilateral infiltrates on CXR. The pushing pressure of the pulmonary capillaries is 35 mm Hg. He is treated with c morphine, or γgen, intravenous nitroglycerin, a cyclic diuretic and 0.25 mg of methyl ester hydrochloride of acci (3ß, 5ß, 14ß, 17ß) -14-amino-3- [(2, -di-O -aceti 1-3, -didesox a-L-mannosyranosyl) -o? i -androstane-7-carboxylic acid per v intravenous every 4 hours for three days, followed by 0. mg of methyl ester hydrochloride of acid (3ß , 5β, 14 17β) -14-amino-3- [(2,4-d i-0-acetyl-3,6-dideoxy-aL-manapyranosyl) -o? I 3-androstane-17-carbo? orally or once a day. She improves in this regimen and is discharged 10 days with dyspnea when she performs mild exercise (soft congestive heart failure, NYHA class II) with 135 follow-up for external patient with a diuretic, ACE inhibitor, nitroglycerin and oral 0.25 mg of methyl ester acid (3ß, 5ß, 14ß, 17ß) -14-amine-3- [(2,4-di-0-acetyl- 3, dideoxy-aL-manop iranosi 1) -o? I 3-androstane-17-carboxyl or by.

EXAMPLE 2 A 44-year-old black man with a history of uncontrolled hypertension for a long time and one year history of moderate congestive heart failure (NYHA class III) presents several episodes of presyncope during the previous weeks. He also complains of fatigue and dispn when he dresses. Medications include digoxin (0. mg / day), lasi? and ACE inhibitor. It presents a gallop of S edema of disseminated ankle corrosion, left ventricular hypertrophy and occasional PVCs on the ECG. • Further evaluation describes frequent multifocal ventricul ectopia and a sustained ventricular tachycardia run in Holter monitoring, a 30% ejection fraction by radionuclide ventridulography and serum digoxin level of 2.2 ng / ml. It is suspected that arrhythmias and pre-syncope are a result of into? Ication by digitalis, and the medication is discontinued. (3ß, 5ß, 14ß, 17ß) -14-amino-3-C (6-deso? 136) hydrochloride was established # 2,3,4-tri-O-aceti 1-a-L-mannopyranosi 1) -o? I 3-androstane-i-carboxyamide in an oral dose of 0.25 mg per day. Due to the persistence of fatigue and dyspnea, the dose is increased during the following six weeks to mg daily additional episodes of pre-syncope, a reduction in PVCs, the absence of non-sustained ventricular tachycardia in second Holter monitoring and an increase in the ejection fraction. to 36%. Her dyspnea with daily activities such as dressing is solved and she is able to work • your garden with occasional soft dyspnea (class II NYH) After a one-year follow-up, your condition remains unchanged.

EXAMPLE 3 A previously healthy Chinese woman of 24 years old presents with a two-month history of dyspnea to the reali * strenuous exercise. There is no family history of heart disease; he does not smoke, and he does not drink alcohol. The normal physical menu except for tachycardia and a maximum impulse point displaced laterally. On the ECG there is a cardiac frequency of 105 and non-specific flattening of the T wave, and the CXR reveals an elongated heart. echocardiogram shows a b i entricular elongation with global hypokinesia and an exuleion fraction of 40%. 137 • valves appear normal. A stress test on a treadmill wheel with limited symptoms shows no evidence of ischemia. A dilated idiopathic cardiomyopathy is diagnosed, class I of NYHA. Initial treatment with an ACE inhibitor produces an intolerable, and therefore is discontinued. (3β, 5β, 14β, 17β) -14-αn-3-androstane-17-carboxylic acid (3-dideoxy-α-mannopyranosyl) -o i 3-androstane-7-carboxylic acid is orally administered at a dose of 2 mg / min. times a day, and during the next month your ability to exercise improves. also an increase in ejection fraction (echocardiogram) to 55%, and an increase in exercise time of 200 seconds in the treadmill test.

EXAMPLE 4 A white man of 55 years of age with a • history of two previous myocardial infarctions and whose pa died suddenly at the age of 50, is being maintained isasorbide dipitrate and a beta blocker with angina stable effort for two years. During the previous month, however, he develops dyspnea by climbing a swelling ankle in the night and dyspnea occasionally nocturnal paraxis. It has a resting heart rate of 9 1+ ankle corrosion edema, a S3 gallop and elongated heart and Kerly B lines in CXR. A diagnosis of mild congestive heart failure (NYHA class) is made due to ischemic heart disease. He suspends his beta blocker by gradual decrease and adds an ACE inhibitor and a diuretic but on this regimen congestive heart failure worsens. Is (3β, 5β, 14β, 17β) -14-amino-3- [(2,3-tridesox i-β-L-mannopyranosyl) -o? and 3-androst-17-carbohydrate orally at a dose of 4 mg per day. Your dyspnea and your ed resolve (class I, NYHA), the heart rate drops to 75, the S3 disappears, the size of your heart decreases, the congestion detected in CXR resolves. There is an increase in the exercise time of 170 seconds in the treadmill test which is carried out afterwards. No aggravation occurs during the next two years.

EXAMPLE 5 A black 60-year-old woman who has a history of three myocardial infarctions and a congestive severs heart failure (class IV, NYHA) has been hospitalized four times in the previous six weeks with acute decompensation despite therapy with do 139 # Therapeutic maximum tolerance of lasix, isosorbide dinitrate, digoxin and an ACE inhibitor. Its symptoms include edema, dyspnea at rest, 3-pad ortoppea marked fatigue and mental confusion. The decision is made to suspend the digoxin and to institute a treatment which is methyl (3ß, 5ß, 14ß, 17ß) -14-amino-3- [(2 ', dideso? I-2', 2'-dif luoro- -L-manop yranosyl) -oi-3-n-threstan-17-carbo-yl. The initial dose of ac (3ß, 5ß, 14ß, 17ß) -14-amino-3-C (2 ', 6'-dideso? I-2' methyl ester, difluora-aL-manno-iranosyl) -oxi] -add-sugar-17-carbax ion of 0.5 mg administered orally once a day, but requires titration to 2 mg three times a day for a period of two months to adequately control symptoms. At the end of the two-month period, her confusion and edema resolve, and she has a better ability to perform daily activities such as dressing herself without dyspnea (NYHA class III, fa moderate cardiac congestive). Your ejection fraction also improves from 20 to 35%. Stays stable for three months 140 EXAMPLE 6 An alcoholic man recently reahbilitated months ago) with a 30-year history of cigarette smoking admitted to the hospital with a three-month history of progressive aggravation of dyspnea when exercising fatigue, orthopnea, ede a and dispnea paro? Ismal nocturnal. You dyspnea while brushing your teeth. The physical examination reveals a cachectic man with moderate distress with respiratory frequency of 30 per minute, a cardiac frequency of 110 beats per minute, blood pressure 90/50, gallop of S3, edema of disseminated corrosion to knees 2+, distension of vein yugul hepatomegaly, ascites, biliary rales and elongated heart. The extensive evaluation provides chronic alcoholic hepatitis diagnosis, chronic pulmonary obstructive disease, and moderate congestive heart failure (class I NYHA) due to toxic (alcoholic) cardiomyopathy. The treatment is begun hydroclaratiazide, an ACE inhibitor and methyl ester acid (3ß, 5ß, 14ß, 17ß) -14-amino-3- [(2 ', 3', 6 '-trideso 2', 2'-dif luoro -aL-mapopyranosyl) -o? i 3-androst non-i7-carboxylic acid at an oral dose of 0.25 mg per day. He quickly and is released in a week. After loss of 6.3 kg he is able to walk to the mailbox with disp 141 mild (class II, NYHA). His respiratory rate is of his heart rate of 90, S3 is no longer heard and edema and rales are resolved. The hpatomega persists unchanged, but the ascites disinuye slightly in the ejection fraction increases from 32 to 45% and the size of the heart decreases.

EXAMPLE 7 It is observed that a sedentary white woman of years of age has an elongated heart that is detected in previously to a surgery scheduled for a cataract. E denies any history of chest pain, dyspnea any history of hypertension, diabetes or heart disease. Your ECG shows changes or specific to the ST-T; normal laboratory normal clinical evaluations. An effort test in an wheel mill has to be terminated due to fatigue without evidence of coronary artery disease. An ecacardiogram with biventricular lengthening, normal valves and a 30% expulsion fraction. It is given a preventive treatment 0.25 mg of methyl ester of acid (3ß, 5ß, 14ß, 17ß) -a ino-3-C ('-deoxy-3', 3 '-di f luoro-aL-manopiranosi1) -o 3-androstane-17-carboyl administered orally per day. fraction of expulsion increases to 40% and is

Claims (6)

142 Attic asinto when he has to be hospitalized for the surge of a second cataract 5 years later. CLAIMS i. Deoxy and oxygenated 14-aminoesteroid compounds and the pharmaceutically acceptable acid salts or esters thereof of the general formula: where a) R? is (i) COOR s wherein Rs is a lower alky group of 1-6 carbon atoms; an lower alkyl group of 1-6 carbon atoms substituted by an amino group; arylalkyl or heteraarylalkyl group or a carbocyclic ani, or • (ii) CHR ^ ÜH wherein RA is a hydrogen atom or a lower alkyl group of 1-6 carbon atoms, or (iii) COR '' ', where R' '' is hydrogen lower alkyl of 1-6 atoms of carbon; amino, lower alkyl of suetituido; amino or dialkylamino and b) Ras is -NR7 a wherein 7 and RA ~ which may be the same or different, are hydrogen atoms or lower alkyl g of 1-6 carbon atoms, and c) R3 is (i) a residue monosaccharide deoxy or substituted oxygen, wherein R9a (R < ", Ri0 and R10ß which may be the same or different are lower alkyl of 1-6 carbohydrogen atoms; hydroxy; fluorine; alkoxy; acetoxy; arylalkyloxy benzo? i; R ^ is a lower alkyl of 1-6 carbon atoms 144 # hydrogen; hydroxy; fluorine; benzoxy; arylalkyl heteroarylalkyl? i; aceto? i or alco? i; wherein, in addition, RB is a lower alkyl of 1-6 carbon atoms, R4, R1 RIA can not be hydro? i or acetoxy; with the additional proviso that when R * m is hydrogen, IO »hydrogen, R ^ and hydrogen; hydro? i or aceto? i and R x hydroxy, acetoxy or alkoxy, RÍO can not be hydroxy acetoxy; Riaj is methyl; acetoxymethyl or hydro? imet il may be a single or double bond, or (ii) a monosaccharide deoxy residue wherein R ^ is arylalkyloxy, heteroarylalkyloxy-oxosilane lower alkyl of C _? replaced, R X? is met and d) R ^ is (i) OH or (ii) H, or 145 # (iii) QRa.3 wherein R 13 is a monosaccharide resi; acetoxy, benzoxy, arylalkyl, heteroarylalkyl and e) S is (i) -CH- where a and b are single bonds (ii) = C where a or b is a double bond.

2. A compound according to claim 1 further characterized in that R is COORs and • is lower alkyl of 1-6 carbon atoms; Rai is NH »; it is a deoxy residue and substituted oxygen, R 12 «R« »R -? . Rio and i * which may be the same different are lower alkyl of 1-6 hydrogen carbon atoms; hydroxy; fluorine; alkoxy; acetoxy; Arylalkyl? heteraarilalquila? i or benzo? i; Rx is a lower alkyl 1-6 carbon atoms; hydrogen; hydro? i; fluorine; benzo? 146 Arylalkyloxy; heteroarylalkyloxy; aceto? i or alkoxy; where in addition when R ß is a lower alkyl of 1-6 carbon atoms, R ^, R ^. ° R x can not be hydroxy or aceto with the additional condition that when R * - *. whether hydrogen is hydrogen, hydrogen, hydroxy or acetoxy and is hydroxy, acetoxy or alkoxy, RIO can not be hydroxy acetaxy; R1SB is methyl; aceto? imetyl or hydro? imethyl; It can be a single or double link.

3. A compound according to claim 2, further characterized in that R «*? hydrogen, R ", is acetoxy, R o is hydrogen, Ri0 hydrogen, R x is acetoxy.

4. A compound according to claim 2, further characterized in that R "*? hydrogen, R9 is arylalkyloxy; Heteroalkylalkyloxy, Ri0 hydrogen, RIO "is hydrogen, R ^ is aceto? i.

5. A compound according to claim 2, further characterized in that R < *? hydrogen, R ", is arylalkyloxy; heteroalloylalkyloxy, RIVER hydrogen, RIVER »is hydrogen, R x x is hydroxy. 6. A compound according to claim 2, further characterized in that * »hydrogen, R«? is hydroxy, RIO is hydrogen, Ri is hydroxy. 7. A compound according to claim 2, further characterized in that Rv «147 hydrogen, R * - is hydroxy, RIO is hydro? i, io * is hydrogen Rn is arylalkyloxy; heteroarylalkyloxy.

6. A compound according to claim 2, further characterized in that R »? hydrogen, R «, is hydrogen, R is hydrogen, Rio * hydrogen, R is arylalkyl?; heteroarylalkyl? i. 9. A compound according to claim 2, further characterized in that R ^? Hydrogen, R «, is hydrogen, RIO is hydrogen, Rlß * hydrogen, R x is hydro? i. 10. A compound according to claim 2, further characterized in that R "5" "hydrogen, R", is hydro? I, RI is hydrogen, R10"hydrogen, R x is hydroxy 11. A compound in accordance with Claim 2, which is also termed because hydrogen, R ,, is hydrogen. is hydrogen and R • arylalkyloxy; heteroarylalkyloxy and benzoxy 12, A compound according to claim 2, further characterized in that hydrogen, R < ? is hydro? i, RAO is hydrogen, R or * hydrogen, n is arylalkyl?, heteroarylalkyl? and benzo? i. 13. A compound according to claim 2, further characterized in that R ^? • hydrogen, R ^ is hydrogen, Ri is hydrogen, Ri * hydrogen, R ^ is alco? I. 14. A compound according to claim 2, further characterized in that R ", m is fluorine methyl. 15. A compound according to claim i, further characterized in that Rx is CDORs Rs is lower alkyl of 1-6 carbon atoms; Rß is Nituted, heteroarylalkyl; and oxosilane lower alkyl of 1-6 atoms of substituted carb and Riat is methyl. 16. A composition according to claim 15 further characterized in that R x arylalkyloxy; heteroarylalkyloxy. 17. A compound according to claim 1, further characterized in that R is COR '' 149 R '' 'is methylamino; Rai is NH »; R3 is a residue of sugar deoxy and substituted oxygen, wherein R ^ ?, R «?, RAO and i * which may be the same or different are lower alkyl of 1-6 hydrogen carbon atoms; hydro? i; fluorine; alkoxy; acetoxy; arylalkyl, heteroarylalkyloxy or benzoy; Rx is a lower alkyl 1-6 carbon atoms; hydrogen; hydroxy; fluorine; benzox arylalkyloxy; heteroarylalkyloxy; acetoxy or alkoxy; Rias methyl; acetoxymethyl or iodoxymethyl; t can be a single or double. 16. A compound according to claim 17, further characterized in that v * hydrogen, R ", is acetoxy or hydroxy; , Rio is acetoxy hydro? I, R10 * is hydrogen, R is aceto? I or hydroxy. 19. A compound according to claim 1 further characterized in that it is selected from the group consisting of ethyl chlorhydrate 150. methyl (3ß, 5ß, 14ß, 17ß) -14-amino-3-C (2,4-di to eti 1-3, -dideso? i-3 ', 3' -difluoro-a-L-mannopyranosyl) ) -o? i 3-apdrostane-17-carboyl; (3ß, 5ß, 14ß, 17 14-amino-3-C (6-deoxy-2, 3, 4-tr i-0-acet i 1-aL-manop iranosi i) oxy) 3-N-met hydrochloride ilapdrostapo-17-carbaxyamide; methyl ester acid (3ß, 5ß, 14ß, i 7ß) -14-amino-3-C (3,6-d idesoxy-a mannopyranosyl) -o? i 3-andrastane-17-carbaxyl Methyl ester of (3ß, 5ß, 14ß, 17ß) -14-amino-3- [(2,3,6-tridesox i-β-mannopyranosyl) -o) 3-androstane-17-carboalicylic acid methyl ester It is methyl (3ß, 5ß, 14ß, 17ß) -14-amino-3- [(2 ', dideso? i-2', 2 '- di f luoro-aL-manop iranasi 1) -oxi 3- androstane-17-carboyl, methyl ester of acid (3ß, 5ß, 14ß, 17 14-amino-3-C (2 ', 3'6'-trideso? i-2', 2'-difluoro-aL- manop iranosi l) -oi-androetano-l 7-carbo? lico; es methyl of acid (3ß, 5ß, 14ß, 17ß) -14-amino-3-C (6'-deso 3 ', 3' -dif luoro -aL-manopiranoei 1) -o? i 3-androstane-17-carbo? lico synthesis of methyl ester maleate of ac (3ß, 5ß, 14ß, 17ß) -14-amino-3-C (3 ', 6' -deoxy-a manopiranosi 1) -ox i 3-androst na-17-carbax 1 ico 20. A pharmaceutical composition characterized by comprising a safe and effective amount of a 15-compound of claim i, or mixtures mism and 5 to 65% and? Pharmaceutically cipients aceptablee. 21. A pharmaceutical composition according to claim 19, further characterized in that Pharmaceutically acceptable excipients are selected from the group consisting of polymers, plasticizers, fillers, binders, lubricants, brighteners, disintegrators, solvents, co-solvent buffer systems, surfactant preservatives, sweetening agents, flavoring agents, dyes or pharmaceutical grade pigments. and viscosity agents. 22. A pharmaceutical composition according to claim 20, further characterized by comprising 15-95% of a compound of claim i mixtures thereof); 0-2% flavoring agents; 0-50% co-solvents; 0-5% of systems of love equalization; -2% surfactants; 0-2% of conservatives; 0-5% sweeteners; 0-5% viscosity agents; o -75% fillers; 0.5 to 2% lubricants; 1-5% brighteners; 4-15% of disintegrators and 1-10% binders. 23. A pharmaceutical composition characterized in that it comprises a safe and effective 15-fold amount of a compound of claim 2, or mixtures of the same and from 5 to 65% of pharmaceutically acceptable ingredients. 24. A pharmaceutical composition according to claim 22, further characterized in that pharmaceutically acceptable excipients are selected from the group consisting of: From the group consisting of polymers, resin plastifiers, fillers, binders, lubricant brighteners, disintegrators, solvents, co-solvent buffer systems, surfactant surfactants, sweeteners, flavoring agents or pharmaceutical grade pigments and viscosity agents. 25. A pharmaceutical composition according to claim 23, further characterized by comprising 15-95% of a compound of claim 2 mixtures thereof); 0-2% flavoring agents; 0-50% co-solvents; 0-5% of damping systems; 0-2% surfactants; 0-2% of conservatives; 0-5% sweeteners; 0-5% viscosity agents; 0-75% fillers; 0.5 to 2% lubricants; 1-5% brighteners; 4-15% of disintegrators and 1-10% binders. 26. A pharmaceutical composition characterized in that it comprises a safe and effective amount from a 15-compound of claim 15, or mixtures thereof, and from 5 to 65% pharmaceutically acceptable ingredients. 27. A pharmaceutical composition according to claim 25, further characterized in that the pharmaceutically acceptable excipients are selected from the group consisting of: • from the group consisting of polymers, resin plastics, fillers, binders, lubricant brighteners, disintegrators, solvents, co-solvent buffer systems, surfactant preservatives, sweetening agents, flavoring agents to pharmaceutical grade pigments and viscosity agents. 26. A pharmaceutical composition according to claim 15, further characterized by comprising 15-95% of a compound of claim 2, mixtures thereof); 0-2% flavoring agents; 0-50% co-solvents; 0-5% of damping systems; 0-2% tepsioactive agents; 0-2% of conservatives; 0-5% sweeteners; 0-5% viscosity agents; 0-75% fillers; 0.5 to 2% lubricants; 1-5% brighteners; 4-15% of disintegrators and 1-10% binders # 29. A pharmaceutical composition characterized in that it comprises a safe and effective amount from 15- of a compound of claim 17, or mixtures thereof, and from 5 to 65% of pharmaceutical excipients. acceptable 30. A pharmaceutical composition according to claim 26, further characterized in that pharmaceutically acceptable excipients are selected. From the group consisting of polymers, resin plasticizers, fillers, binders, lubricant brighteners, disintegrators, solvents, co-solvent buffer systems, surfactant preservatives, sweetening agents, flavoring agents to pharmaceutical grade pigments and viscosity agents. 31. A pharmaceutical composition according to claim 17, further characterized by comprising 15-95% of a compound of claim 2, mixtures thereof); 0-2% flavoring agents; 0-50% co-solvents; 0-5% of damping systems; 0-2% surfactants; 0-2% of conservatives; 0-5% sweeteners; 0-5% viscosity agents; 0-75% fillers; 0.5 to 2% lubricants; 1-5% brighteners; 4-15% disintegrators and 1-10% binders 32. A method for treating humans and other mammals affected by a congestive heart failure characterized in that it comprises administering to a human or other mammal a safe and effective amount of the pharmaceutical composition. of claim 19. 33. A method for treating human and other mammals affected by a congestive cardiac failure characterized in that it comprises administering to the patient a mammalian body. human or other mammal a safe and effective amount the pharmaceutical composition of claim 22. 34. A method for treating human beings and other mammals affected by congestive heart failure characterized in that it comprises administering to said human or other mammal a quantity Sure and Effective Pharmaceutical Composition of Claim 25. 35. A method for treating human and other mammals affected by cardiac congestive failure characterized in that it comprises administering to a human or other mammal a safe and effective amount of the pharmaceutical composition of claim 26. 36. The use of a compound having structure: as a starting material or intermediate in the synthesis of compound according to claim 1. 37. The use of a compound according to claim 36 as a starting material in the composite synthesis having the following structure: 36. A compound according to claim 36 further characterized by having * structure: and is synthesized using the following method: (a) 2,3,4-tribenzaate 6-deoxy-a-L-manapyranosyl; DMSO; base selected from the group including amide tertiary, amidines, bicarbonates, carbonates, heteroa amine and a solvent selected from the group consisting of chlorinated solvents, aromatic hydrocarbons, esters and ethers in a slurry heated to 50-150 ° C; (b) agi the reaction mixture at 50-150 ° C for 5 minutes at 157 • minutes; (c) pouring the reaction mixture over ice water and (d) extracting the product with a solvent selected from the group consisting of clorad aromatic hydrocarbon solvents, esters, ethers and evaporating the layer to give a solid. 39. A compound according to claim 36 further characterized in that the solvent step (a) is removed and the amounts DMSO are increased so that the DMSO is used as reagent and c • solvent. 40. A compound according to claim 36 further characterized in that the solvent step (a) is dimethoxyethane. 41. A compound according to claim 36 further characterized in that the temperature of the reaction mixture in steps (a) and (b) is 90 ° C. 42. A compound according to claim 41 further characterized in that the temperature is about 70 ° C. 43. A compound according to claim 36 further characterized in that the step solvent (d) is EtOAc. 44. A compound according to claim 36 further characterized in that the base * step (a) is triet ila ina. 45. A compound according to claim 36 further characterized in that: i) p (a) is driven with 2,3,4-tri-O-benzoate of 6-deoxy-a-anopyranosyl and DMSO in addition because DMSO is used in such quantities that it can be used as reagent and solvent; 2) the reaction mixture in steps (a) and (b) is heated and stirred at about 70 ° C; 3) the extraction in step (d) is carried out with EtOAc; and 4) the solution of • base used in step (a) is triethanolamine. 159 • COMPOUNDS 14-AMINOESTERQIDES NOVEDOSOS DESOXI AND OXÍGENO- SUBSTITUIDOS CONTAIN SUGAR EXTRACT OF THE DESCRIPTION * Csmpueetos 14-aminoesteroids novel deso? I and o? Ígen replaced and the acid salts or esters 160 may be a single or double bond, or (ii) a deoxy or oxygen-substituted monosaccharide residue wherein R is arylalkyloxy, heteroarylalkyl loxy or oxosilane lower alkyl of Cj._A substituted, R? ai e methyl and d) R ^ is (i) OH or (ii) H, or (iii) ORjLa wherein R13 is a residue monosaccharide; acetoxy, benzoxy, arylalkyl. or heteroarylalkyl and e) Z is (i) -CH- where a and b are simple bonds (ii) C where a or b is a double link. 161 they are the same or different, they are hydrogen atoms or lower alkyl group of 1-6 carbon atoms, and) Ra is (i) a deoxy or substituted o-substituted monosaccharide residue, wherein RV 1 R ^, RÍO and Ri * l ° s which may be the same or different are lower alkyl of 1-6 carbon atoms; hydrogen; hydro? i; fluorine; alkoxy; acetoxy; Arylalkyloxy or benzoxy; R x is a lower alkyl of 1-6 carbon atoms; hydrogen; hydroxy; fluorine; benzo? i; Arylalkyloxy; heteroarylalkyloxy; acetoxy or alkoxy; where also when Rs is a lower alkyl of 1-6 carbon atoms, R "V, R" ".l, i can not be hydro? I or aceto? I; with the additional proviso that when R ^ m is hydrogen, R * is hydrogen, R ^ is hydrogen; hydro? i or aceto? i and Rx is hydro? i, acetoxy or alkoxy, RJLO can not be hydroxy or aceto? i; R? A. be methyl; aceto? imet ilo or hydro? imet ilo; t 162 pharmaceutically acceptable of the same of the general formula: where a) Rx is (i) COOR? wherein Ra is a lower alkyl group of 1-6 carbon atoms; a lower alkyl group of 1-6 carbon atoms substituted by an amino group; an arylalkyl or heteroarylalkyl group or a ring • carbocyclic, or (i i) CHR? OH wherein RA is a hydrogen atom or a lower alkyl group of 1-6 carbon atoms, or (iii) COR '' ', wherein R' '' is hydrogen; lower alkyl of 1-6 carbon atoms; amino, lower alkyl of C¿-? replaced; amino or dialkylamino and b) R-a is -NR7R? where R7 and Rß, which can