RU2057126C1 - Benzimidazole derivatives, method of their synthesis and pharmaceutical composition on their basis - Google Patents

Abstract

FIELD: organic chemistry. SUBSTANCE: product: derivatives of benzimidazole of the formula I at the corresponding radical values R₁- R₃, and a method of their synthesis by interaction of compound of the formula II with compound R′-Y. Synthesized compounds were used in pharmacology. Structure of compounds of the formulas I and II is given in invention description. EFFECT: improved method of synthesis. 42 cl

Description

 The subject of the invention are novel benzimidazole derivatives having excellent pharmaceutical properties and intermediates for their synthesis.

(I) где R₁ представляет вариантно замещенную алкильную группу; каждый из элементов R₂ и R₃ представляет группу, способную образовывать анион, или группу, которая может быть превращена в такую группу; кольцо А представляет бензольное кольцо, которое кроме группы, обозначенной символом R₂, вариантно включает другие заместители, а Х обозначает прямую связь фениленовой группы и фенильной группы или связь через пространственную группу, цепь атомов которой не превышает 2, или их соли, которые обладают сильным антагонизмом в отношении ангиотензина II и гипотензивным действием и являются полезными в качестве терапевтических средств для лечения болезней, связанных с расстройством кровообращения, таких как гипертонические болезни, сердечно-сосудистые заболевания, кровоизлияние в мозг и т.д.In particular, the invention provides compounds of the formula

(I) where R ₁ represents a variant substituted alkyl group; each of the elements R ₂ and R ₃ represents a group capable of forming an anion, or a group that can be converted into such a group; ring A represents a benzene ring, which, in addition to the group indicated by the symbol R ₂ , optionally includes other substituents, and X denotes a direct bond of the phenylene group and the phenyl group or a bond through a space group whose atom chain does not exceed 2, or their salts, which have a strong antagonism of angiotensin II and hypotensive effect and are useful as therapeutic agents for the treatment of diseases associated with circulatory disorders, such as hypertension, cardiac convulsive diseases, cerebral hemorrhage, etc.

In homeostasis, the reninangiotensin system is used along with the aldosterone system to regulate blood pressure, the amount of fluid in the body, and the balance between electrolytes. The relationship between the reninangiotensin system and hypertension is based on the fact that an angiotensin II conversion inhibitor (AP) inhibitor (ACE), an angiotensin II forming enzyme, has a strong vasoconstrictor effect. Since angiotensin II increases blood pressure through angiotensin II receptors on the cell membrane, angiotensin II antagonists, like ACE inhibitors, can be used to treat hypertension. It is known that many substances related to angiotensin II, such as saralazine and Sar ¹ , Ala ⁸ / AP, have strong antagonism against angiotensin II. However, peptide antagonists are characterized by a short period of action after parenteral administration and are ineffective when taken orally (Ondetti M.A. and Kushman D.V. Annual reports on clinical biochemistry, 13, 82-91 (1978)).

 On the other hand, to solve the problems characteristic of these peptide antagonists, non-peptide angiotensin II antagonists have been investigated. As one of the earliest studies in this area, mention is made of imidazole derivatives that are antagonistic to angiotensin II, which are described in unexamined publication of Japanese patents NN 71073/1981, 71074/1981, 92270/1982 and 157768/1983, in US patent N 4355040 and US Pat. No. 4,340,598. Further improved imidazole derivatives are discussed in European Patent No. 0253310, European Patent No. 0291969, European Patent No. 0324377, and Unexamined Japanese Patent Publication Nos. 23863/1988 and 117876/1989. And in European patent N 0323841 and in the unexamined publication of Japanese patent N 287071/1989, derivatives of pyrrole, pyrazole and triazole are described as antagonists of angiotensin II.

 According to the authors, compounds that are clinically useful for the treatment of diseases associated with circulatory disorders, such as hypertension, cardiovascular disease and cerebral hemorrhage, should exhibit antagonism to angiotensin II receptors, have strong antagonism to angiotensin II and hypotensive effect oral administration, so they comprehensively investigated the non-peptide angiotensin II receptor antagonists with these considerations in mind.

 In addition, US Pat. No. 4,880,804 discloses benzimidazole derivatives that are antagonistic to angiotensin II receptors and are effective in treating rats suffering from renal hypertension when given intravenously, for example, compound A having a hydroxymethyl, methoxy, formyl, chlorine or carboxyl group in positions 5 and / or 6. However, most compounds A are not active when administered orally, with only 6-hydroxymethyl compounds and 6-chlorine compounds being ciency when administered orally (100 mg / kg or less). However, compounds having the above activity are unsatisfactory for practical use as medicines.

(A)
В указанном патенте США специально отмеченные соединения, включающие соединения А, ограничены бензимидазолом, имеющим заместители в положениях 5 и/или 6 бензольного кольца, при этом в нем не рассматриваются производные бензимидазола, имеющие заместители в положении 4 или 7.

(A)
In said U.S. patent, specially marked compounds including compounds A are limited to benzimidazole having substituents at positions 5 and / or 6 of the benzene ring, and benzimidazole derivatives having substituents at position 4 or 7 are not considered.

 Certain compounds, i.e. 7-substituted benzimidazole derivatives, which were not specifically indicated in US Pat. No. 4,880,804, have strong antagonism to angiotensin II receptors, and when administered orally, they show unexpectedly strong antagonism to angiotensin II and hypertensive effects that were not observed in derivatives substituted in provisions 5 and / or 6.

в которой R₁ представляет вариантно замещенную алкильную группу; элементы R₂ и R₃ независимо друг от друга представляют группу, способную образовывать анион, или группу, которая может быть превращена в такую группу; кольцо А представляет бензольное кольцо, которое кроме группы, обозначенной символом R₂ вариантно включает другие заместители; а Х обозначает прямую связь фениленовой группы и фенильной группы или связь через пространственную группу, цепь атомов которой не превышает 2, или их соли.The subject of the invention are compounds of the formula

in which R ₁ represents a variant substituted alkyl group; the elements R ₂ and R ₃ independently from each other represent a group capable of forming an anion, or a group that can be converted into such a group; ring A represents a benzene ring which, in addition to the group indicated by R _2, optionally includes other substituents; and X denotes a direct bond of the phenylene group and the phenyl group, or a bond through a space group whose atom chain does not exceed 2, or their salts.

It can be seen from general formula 1 that the alkyl group denoted by R ₁ includes straight or branched chain lower alkyl groups having from 1 to 8 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl , tert-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, etc. Alkyl groups may be substituted by a hydroxyl group, optionally substituted by an amino group, a halogen, a lower (C _1-4 ) alkylthio group or a lower (C _1-4 ) alkoxy group. Preferred groups denoted by R ′ ₁ are lower (C _2-5 ) -alkyl groups optionally substituted with a hydroxyl group, an amino group, a halogen and a lower (C _1-4 ) alkoxy group.

COR″″ в которой R''' представляет водород, низшую (С_1-4)-алкильную группу с прямой или разветвленной цепью (например, метил, этил, н-пропил, изопропил, н-бутил, изобутил, втор-бутил, трет-бутил, н-пентил, изопентил, неопентил и т.д.), или (С_5-7)-циклоалкильную группу (например, циклопентил, циклогексил, циклогептил и т.д.), а R"" представляет низшую (С_1-6)-алкильную группу с прямой или разветвленной цепью (например, метил, этил, н-пропил, изопропил, н-бутил, изобутил, втор-бутил, трет-бутил, н-пентил, изопентил, неопентил и т.д.), (С_5-7)-циклоалкильную группу (например, циклопентил, циклогексил, циклогептил и т.д.), низшую (С_1-3) -алкильную (например, метил, этил, н-пропил, изопропил и т. д. ) или низшую (С_2-3)-алкенильную группу (например, винил, пропенил, аллил, изопропенил и т.д.),замещенную (С_5-7)-циклоалкилом (например, циклопентилом, циклогексилом, циклогептилом и т.д.) или фенильной группой, вариантно замещенную фенильную группу (например, фенил и т.д.), низшую (С_1-6)- алкоксильную группу с прямой или разветвленной цепью (например, метокси, этокси, н-пропокси, изопропокси, н-бутокси, изобутокси, втор-бутокси, трет-бутокси, н-пентилокси, изопентилокси, неопентилокси и т.д.), (С_5-7)-циклоалкилоксигруппу (например, циклопентилокси, циклогексилокси, циклогептилокси и т.д.), низшую (С_1-3)-алкоксильную группу (например, метокси, этокси, н-пропокси, изопропокси и т. д. ), замещенную (С_5-7)-циклоалкилом (например, циклопентилом, циклогексилом, циклогептилом и т.д.), или фенильной группой, вариантно замещенную феноксильную группу (например, фенокси и т.д.) или вариантно замещенную бензилоксигруппу (например, бензилокси и т.д.) низшую (С_1-6)-алкоксильную группу, низшую (С_1-6)-алкилтиогруппу или вариантно замещенный диоксоленил (например, 5-метил-2-оксо-1,3-диоксолен-4-ил и т.д.), предпочтительно низшую (С_1-6)-алкоксильную группу, алкильная часть которой может быть замещена гидроксильной группой, вариантно замещенной аминогруппой, галогеном, низшей (С_2-6)-алканоилоксигруппой, 1-низшей (С_1-6)-алкоксильной группой, низшей (С_1-6)-алкилтиогруппой или низшей (С_1-6)-алкоксикарбонилоксигруппой) и n означает 0 или 1] цианогруппу, вариантно защищенный (например, алкильной или ацильной группой) тетразолил, фосфорную кислоту, сульфокислоту, фенильную гидроксильную группу, вариантно замещенную алкоксильную группу, амид трифторметансульфокислоты и низшую (С_1-3)-алкильную группу, вариантно замещенную гидроксильной группой или вариантно замещенной аминогруппой. Группы, способные образовывать анион, или группы, которые можно превратить в такие группы биологическим путем, т.е. в результате физиологического или химического метаболизма (например, посредством окисления, восстановления или гидролиза), также входят в объем значений R₂ и соединение 1, в котором R₂ представляет группу, способную образовывать анион, или группу, которую можно превратить в такую группу химическим путем, также является полезным в качестве промежуточного соединения, предназначенного для синтеза этого соединения.Examples of a group capable of forming an anion, or a group that can be converted to such a group indicated by R ₂ , include a group represented by the formula
(CH ₂ ) _n CO-D in which D represents hydrogen, a hydroxyl group, a variant substituted amino group, a halogen or a variant substituted alkoxy group (for example, a lower (C _1-6 ) alkoxy group, the alkyl part of which may be substituted by a hydroxyl group, optionally substituted amino group, halogen, group of the formula
-O

COR ″ ″ wherein R ″ ″ represents hydrogen, a straight or branched chain lower (C _1-4 ) alkyl group (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, etc.), or a (C _5-7 ) cycloalkyl group (e.g. cyclopentyl, cyclohexyl, cycloheptyl, etc.), and R "" represents lower ( A straight or branched C _1-6 ) alkyl group (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, etc. d.), (C _5-7 ) -cycloalkyl group (e.g. example, cyclopentyl, cyclohexyl, cycloheptyl, etc.), lower (C _1-3 ) -alkyl (e.g. methyl, ethyl, n-propyl, isopropyl, etc.) or lower (C _2-3 ) - an alkenyl group (e.g., vinyl, propenyl, allyl, isopropenyl, etc.) substituted with (C _5-7 ) -cycloalkyl (e.g., cyclopentyl, cyclohexyl, cycloheptyl, etc.) or a phenyl group, optionally substituted with a phenyl group (e.g., phenyl etc.), a lower (C _1-6) - alkoxy group with a straight or branched chain alkyl (e.g., methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, t a-butoxy, n-pentyloxy, isopentyloxy, neopentyloxy etc.), (C _5-7) -tsikloalkiloksigruppu (e.g., cyclopentyloxy, cyclohexyloxy, cycloheptyloxy etc.), a lower (C _1-3) alkoxy a group (e.g., methoxy, ethoxy, n-propoxy, isopropoxy, etc.) substituted with (C _5-7 ) cycloalkyl (e.g., cyclopentyl, cyclohexyl, cycloheptyl, etc.), or a phenyl group optionally substituted a phenoxy group (e.g., phenoxy, etc.) or a variant substituted benzyloxy group (e.g., benzyloxy, etc.) lower (C _1-6 ) alkoxy group, lower A (C _1-6 ) alkylthio group or a variant substituted dioxolenyl (e.g. 5-methyl-2-oxo-1,3-dioxolen-4-yl, etc.), preferably a lower (C _1-6 ) alkoxy group the alkyl part of which may be substituted by a hydroxyl group, optionally substituted by an amino group, a halogen, a lower (C _2-6 ) alkanoyloxy group, a 1-lower (C _1-6 ) alkoxy group, a lower (C _1-6 ) alkylthio group or a lower (C _1-6 ) alkoxycarbonyloxy group) and n is 0 or 1] cyano optionally protected (for example, with an alkyl or acyl group) tetrazolyl, phosphoric acid, with Ulfonic acid, phenyl hydroxyl group, optionally substituted alkoxy group, trifluoromethanesulfonic acid amide and lower (C _1-3 ) -alkyl group, optionally substituted by hydroxyl group or optionally substituted amino group. Groups capable of forming an anion, or groups that can be converted into such groups biologically, i.e. as a result of physiological or chemical metabolism (for example, by oxidation, reduction or hydrolysis), R ₂ and compound 1, in which R ₂ represents a group capable of forming an anion, or a group that can be chemically converted to such a group, are also included is also useful as an intermediate compound for the synthesis of this compound.

Preferred groups indicated by the symbol R ₂ include groups represented by the formula (CH ₂ ) _n CO-D, [wherein D represents hydrogen, hydroxyl group, amino group, N-lower C _1-4 ) -alkylamino, N, N-lower A (C _1-4 ) dialkylamino group or a lower (C _1-6 ) alkoxy group, the alkyl part of which is optionally substituted with a hydroxyl group, an amino group, a halogen, a lower (C _2-6 ) alkanoyloxy, 1-lower (C _1-6 ) alkoxy group, a lower (C _1-6) alkylthio or lower (C _1-6) -alkoksikarboniloksigruppoy, and n represents 0 or 1] or tetrazolyl, alternatively with aschischenny alkyl (e.g., lower (C _1-4) -alkyl and t. d.) or acyl (e.g. lower (C _2-5) alkanoyl or benzoyl). In addition, preferred groups are groups represented by the formula
-CO-D 'in which D' represents a hydroxyl group, an amino group, an N-lower (C _1-4 ) alkylamino group, a lower (C _1-4 ) dialkylamino group or a lower (C _1-6 ) alkoxy group, an alkyl part which is optionally substituted by a hydroxyl group, an amino group, a halogen, a lower (C _2-6 ) alkanoyloxy group, a 1-lower (C _1-6 ) alkoxy group, a lower (C _1-6 ) alkylthio or lower (C _1-6 ) -alkoxycarbonyloxy] or tetrazolyl, optionally protected by an alkyl or acyl group.

Examples of groups capable of forming an anion, or groups that can be converted to those groups expressed by the element R ₃ , include carboxide, tetrazolyl, trifluoromethanesulfonic acid amide (-NHSO ₂ CF ₃ ), phosphoric acid, sulfonic acid, cyano or lower (C _1-4 ) -alkoxycarbonyl group, moreover, these groups are optionally protected by a variantly substituted lower alkyl group or an acyl group as long as they are able to form an anion, or groups that can be converted into such groups by biological means, i.e. under physiological conditions or chemically.

Compounds I, in which R ₃ represents a group capable of forming an anion, or a group that can be converted into such a group (e.g., cyano group) chemically (e.g., by oxidation, reduction, or hydrolysis), are useful as intermediates intended for the synthesis of these compounds.

Preferred groups indicated by R ₃ are carboxyl or tetrazolyl.

- и R представляет водород, вариантно замещенную низшую алкильную группу (например, низшую (С_1-4)-алкильную группу, вариантно замещенную гидроксильной группой, вариантно замещенной аминогруппой, галогеном, низшей (С_1-4)-алкоксильной группой и т.д.) или группы, представленные формулой -CO-D, [в которой D представляет водород, вариантно замещенную алкоксильную группу [например, низшую (С_1-4)-алкоксильную группу, вариантно замещенную вариантно замещенной аминогруппой, гидроксильной группой, галогеном, низшей (С_1-4)-алкоксильной группой и т.д. вариантно замещенную аминогруппу [например, амино, N-низшую (С_1-4)- алкиламиногруппу (например, метиламино), N,N-низшую (С_1-4)-диалкиламиногруппу (например, диметиламино), N-ариламиногруппу (например, фениламино), алициклическую аминогруппу (например, морфолино, пиперидино, пиперазино или N-фенилпиперазино) и т.д. галоген (например, хлор и т.д.) или гидроксильную группу Из этих групп предпочтение отдается галогену, низшей (С_1-4)-алкильной группе, низшей (С_1-4)-алкоксильной группе, нитрогруппе или группам, представленным формулой -СО-D", [в которой D" представляет гидроксильную группу или низшую (С_1-2)-алкоксильную группу] или аминогруппе, вариантно замещенной низшим (С_1-4)-алкилом, причем наиболее предпочтительными являются галоген и низший (С_1-4)-алкил.Examples of substituents on the benzene ring A, in addition to the groups indicated by the symbol R ₂ , include halogen (eg, F, Cl, Br, etc.), a nitro group, a cyano group, alternatively substituted amino groups [for example, amino, N-lower (C _{1- 4} ) alkylamino (e.g. methylamino, etc.), N, N-lower (C _1-4 ) dialkylamino (e.g. dimethylamino, etc.), N-arylamino (e.g. phenylamino, etc. .), an alicyclic amino group (for example, morpholino, piperidino, piperazino, N-phenylpiperazino, etc.)] of the group represented by the formula -YR, [where Y denotes a linking group of atoms -0-, -S- or

- and R represents hydrogen, optionally substituted lower alkyl group (for example, lower (C _1-4 ) -alkyl group, optionally substituted by hydroxyl group, optionally substituted by amino group, halogen, lower (C _1-4 ) alkoxy group, etc. .) or groups represented by the formula —CO — D, [wherein D is hydrogen, a variant substituted alkoxy group [for example, a lower (C _1-4 ) alkoxy group optionally substituted by a variant substituted amino group, a hydroxyl group, a halogen, lower ( With _1-4 ) alkoxy group, etc. a variant substituted amino group [eg amino, N-lower (C _1-4 ) alkylamino group (eg methylamino), N, N-lower (C _1-4 ) dialkylamino group (eg dimethylamino), N-arylamino group (eg phenylamino), an alicyclic amino group (for example, morpholino, piperidino, piperazino or N-phenylpiperazino), etc. halogen (e.g. chlorine, etc.) or hydroxyl group. Of these groups, halogen, a lower (C _1-4 ) alkyl group, a lower (C _1-4 ) alkoxy group, a nitro group or the groups represented by the formula - CO-D ", [in which D" represents a hydroxyl group or a lower (C _1-2 ) alkoxy group] or an amino group optionally substituted with lower (C _1-4 ) alkyl, with halogen and lower (C ₁ being most preferred) _-4 ) -alkyl.

- -O- -S- -

- -

-

-
-O-

- -S-

и -

=

-
Среди соединений вышеуказанной формулы I предпочтение отдается соединениям формулы I'

(I') [в которой R₁ представляет низший (С_2-5)-алкил, вариантно замещенный гидроксильной группой, аминогруппой, галогеном или низшей (С_1-4)-алкоксильной группой, R₂ представляет группу, выраженную формулой -СО-D', [в которой D' обозначает гидроксильную группу, аминогруппу, N-низшую (С_1-4)-алкиламиногруппу, N,N-низшую (С_1-4)-диалкиламиногруппу или низшую (С_1-4)-алкоксильную группу, алкильная часть которой вариантно замещена гидроксильной группой, аминогруппой, галогеном или низшей (С_1-4)-алкоксильной группой] или тетразолильную группу, вариантно защищенную алкильной или ацильной группой; R₃ обозначает карбоксильную или тетразолильную группу, вариантно защищенную алкильной или ацильной группой; и R₁ обозначает водород, галоген, низшую (С_1-4)-алкильную группу, низшую (С_1-4)-алкоксильную группу, нитрогруппу, группу, представленную формулой: -СО-D"' [в которой D"' обозначает гидроксильную группу или низшую (С_1-2)-алкоксильную группу] или аминогруппу, вариантно замещенную низшим (С_1-4)-алкилом, предпочтительно водородом, низшим (С_1-4)-алкилом, галогеном и предпочтительнее водородом)]
Способ получения
Соединения, имеющие общую формулу I, можно получить в соответствии с рассматриваемыми ниже способами.X shows that the adjacent phenylene group has a direct connection with the phenyl group or is connected with it through a space group, the chain of atoms of which is equal to 2 or less. As a spatial group, any group having a diatomic chain in which the number of atoms forming a straight chain is 1 or 2, and this group may have a side chain, can be mentioned. In particular, an example of such a group is lower (C _1-4 ) alkylene,
-

- -O- -S- -

- -

-

-
-O-

- -S-

and -

=

-
Among the compounds of the above formula I, preference is given to compounds of the formula I '

(I ') [in which R ₁ represents lower (C _2-5 ) -alkyl optionally substituted with a hydroxyl group, an amino group, halogen or a lower (C _1-4 ) alkoxy group, R ₂ represents a group represented by the formula —CO— D ', [in which D' represents a hydroxyl group, an amino group, an N-lower (C _1-4 ) alkylamino group, N, an N-lower (C _1-4 ) dialkylamino group or a lower (C _1-4 ) alkoxy group whose alkyl moiety alternatively with substituted hydroxyl group, amino group, halogen or a lower (C _1-4) alkoxy group], or a tetrazolyl group, alternatively with reserved hydrochloric alkyl or acyl group; R ₃ represents a carboxyl or tetrazolyl group optionally protected by an alkyl or acyl group; and R ₁ is hydrogen, halogen, a lower (C _1-4 ) alkyl group, a lower (C _1-4 ) alkoxy group, a nitro group, a group represented by the formula: —CO — D ″ ″ [in which D ″ is hydroxyl group or a lower (C _1-2 ) alkoxy group] or an amino group optionally substituted with lower (C _1-4 ) -alkyl, preferably hydrogen, lower (C _1-4 ) -alkyl, halogen and preferably hydrogen)]
Production method
Compounds having the general formula I can be prepared according to the methods described below.

R

в которой R₁, R₂, R₃, А и Х имеют указанные выше значения, а W обозначает атом галогена.Reaction a

R

in which R ₁ , R ₂ , R ₃ , A and X have the above meanings, and W denotes a halogen atom.

в которой каждый символ имеет указанное выше значение.Reaction b

in which each character has the meaning indicated above.

в которой R₁, R₂, R₃, А и Х имеют указанные выше значения, а R₅ обозначает вариантно замещенный низший (С_1-4)-алкил.Reaction with

in which R ₁ , R ₂ , R ₃ , A and X are as defined above, and R ₅ is optionally substituted lower (C _1-4 ) -alkyl.

в которой каждый символ имеет указанное выше значение.Reaction d

in which each character has the meaning indicated above.

в которой R₁, R₂, R₃, A и Х имеют указанные выше значения, а Y представляет иминоэфир, иминотиэфир, карбоксил, амидин, цианогруппу и т.д.Reaction e

in which R ₁ , R ₂ , R ₃ , A and X have the above meanings, and Y represents iminoether, iminothiester, carboxyl, amidine, cyano group, etc.

в которой R₁, R₃, R₅, A и Х имеют указанные выше значения, а n означает 0 или 1.Reaction f

in which R ₁ , R ₃ , R ₅ , A and X have the above meanings, and n means 0 or 1.

в которой каждый символ имеет указанное выше значение.Reaction g

in which each character has the meaning indicated above.

в которой R₁, R₃, А и Х имеют указанные выше значения, а W представляет атом галогена.Reaction h

in which R ₁ , R ₃ , A and X have the above meanings, and W represents a halogen atom.

в которой R₁, R₃, A, X и W имеют указанные выше значения.Reaction i

in which R ₁ , R ₃ , A, X and W have the above meanings.

в которой R₁, R₃, A, X и W имеют указанные выше значения, а R₆ представляет низшую алкоксильную группу, низшую алкилтиогруппу, вариантно замещенную аминогруппу или цианогруппу.Reaction j

in which R ₁ , R ₃ , A, X and W have the above meanings, and R ₆ represents a lower alkoxyl group, a lower alkylthio group, a variant substituted amino group or a cyano group.

в которой R₁, R₃, A и Х имеют указанные выше значения, а R₇представляет низшую алкильную группу.Reaction k

in which R ₁ , R ₃ , A and X have the above meanings, and R ₇ represents a lower alkyl group.

в которой R₁, R₃, R₇, A и Х имеют указанные выше значения, а n означает 0 или 1.Reaction l

in which R ₁ , R ₃ , R ₇ , A and X have the above meanings, and n means 0 or 1.

 The above reaction a is an alkylation using an alkylating agent III in an organic solvent and in the presence of a base.

 This reaction is usually carried out in a solvent such as dimethylformamide, dimethylacetamide, dimethyl sulfoxide, acetonitrile, acetone or ethyl methyl ketone, using from 1 to 3 mol of base and from 1 to 3 mol of alkylating agent III, based on 1 mol of compound II.

 As the base used, for example, sodium hydride, tert-butoxypotassium, potassium carbonate or sodium carbonate.

 The alkylating agent III is used in the form of a substituted halide (e.g., chloride, bromide and iodide), but it can be used in the form of a substituted sulfonic acid ester (e.g., p-toluenesulfonic acid methyl ester).

 Although the reaction conditions vary depending on the combination of base and alkylating agent III, this reaction is usually carried out at temperatures from ice cooling to room temperature for 1-10 hours.

 Reaction b is the reaction of a cyano group introduced into the benzene ring of compound Ia with various azides, resulting in the formation of a tetrazole Ib compound.

 This reaction is usually carried out in a solvent, for example dimethylformamide, dimethylacetamide, toluene or benzene, using from 1 to 3 mol of the azide compound, based on 1 mol of the compound Ia.

 Examples of these azides include trialkyltin azide, triphenyltin azide, or nitric acid.

When using organotin azide, this reaction is carried out in toluene or benzene under reflux for 10-30 hours. When using nitric acid, sodium azide and ammonium chloride are used in twice the number of moles in terms of compound Ia. This reaction is carried out in dimethylformamide at a temperature of from 10 to 30 ^about C for 1-3 days. An appropriate amount of sodium azide and ammonium chloride is preferably added to this reaction system in order to accelerate this reaction.

Reaction c serves to produce carboxylic acid Id by hydrolysis of the ester Ic in the presence of alkali. This reaction is carried out in aqueous alcohol (for example, methanol, ethanol or methyl cellosolve) using 1 to 3 mol of alkali in terms of 1 mol of compound Ic. As alkali, along with other substances, sodium hydroxide and potassium hydroxide can be used. This reaction is preferably carried out at temperatures from room temperature to 100 ^about C.

 Reaction d serves to obtain a benzimidazole derivative I by reduction of a nitro group followed by intramolecular cyclodehydration.

 This reaction is carried out using from 2 to 10 mol of a reducing agent in terms of 1 mol of compound IV. As the reducing agent, a metal such as iron, zinc or tin can be mentioned. This reaction is usually carried out under acidic or alkaline conditions. Alcohols (e.g., methanol and ethanol), ethers (e.g., dioxane and tetrahydrofuran) and acetic acid or hydrochloric acid, individually or in a mixed solution, are used as a solvent.

Reaction conditions vary depending on the combination of reducing agent, solvent and acid (or alkali). This reaction usually proceeds at temperatures from room temperature to 100 ^about C for 1-5 hours

After completion of cyclodehydration after the reduction reaction preferably produce heat for 2-3 hours at 50 ^to 100 ° C under acidic conditions.

 Reaction e is the cyclization of the diamine compound V with various compounds in an organic solvent to form the benzimidazole compound I.

 The above various compounds include carboxylic acid, aldehyde, orthoester, iminoether and iminothioether.

 These reagents are usually used in an amount of 1-10 mol based on 1 mol of compound V. This reaction usually proceeds in an organic solvent, but the reagent can be used in a double amount compared to the solvent.

 Organic solvents that vary depending on the reagent used include alcohols (methanol, ethanol, etc.), cellosolves (methyl cellosolve, ethyl cellosolve, etc.), halogenated hydrocarbons (chloroform, methylene chloride, etc.), ethers (dioxane, tetrahydrofuran, etc.), aromatic hydrocarbons (benzene, toluene), acetonitrile and dimethylformamide, along with other substances.

 To accelerate the reaction, an acid (hydrochloric acid, sulfuric acid, paratoluene sulfonic acid, etc.) or a base (triethylamine, pyridine, sodium methylate, sodium ethylate, potassium carbonate, etc.) can be added to the reaction system.

 Although the reaction conditions vary depending on the reagents used, this reaction is preferably carried out at temperatures from room temperature to the boiling point of the solvent used for 1-10 hours

 Reaction f serves to produce If carboxylic acid by hydrolysis of Ie ester in the presence of alkali.

 This reaction is usually carried out in aqueous alcohol (e.g., methanol, ethanol, methyl cellosolve, etc.) using 1 to 3 mol of alkali in terms of 1 mol of compound Ie. Sodium hydroxide and potassium hydroxide are used as alkali.

This reaction is preferably carried out at temperatures from room temperature to 100 ^about C for 1-10 hours

 Reaction g serves to produce the hydroxymethyl compound Ig by reducing the carboxylic acid ester Ie.

This reaction is carried out using from 1 to 5 mol of a reducing agent in terms of 1 mol of compound Ie. As the reducing agent, for example, lithium aluminum hydride or sodium borohydride can be mentioned. In the case of using the first substance, an ether (tetrahydrofuran, dioxane, ethyl ether, etc.) is usually used as a solvent. This reaction proceeds for 1-20 hours at room temperature to the boiling point of the solvent used. If the latter compound is used, ether (tetrahydrofuran and dioxane) or alcohol (ethanol, butanol, etc.) is used as a solvent, and an appropriate amount of methanol is preferably added to the reaction system to accelerate the reaction. This reaction proceeded for 1-20 hours at temperatures from room temperature to the reflux temperature of the solvent used, preferably from 50 ^{° C} to the reflux temperature of the solvent.

 Reaction h serves to produce compound Ih by halogenating the Ig compound with a halogenating reagent in an organic solvent.

 Examples of organic solvents include, among other substances, halogenated hydrocarbons, such as dichloromethane, chloroform or dichloroethane, and ethers, such as ethyl ether, tetrahydrofuran or dioxane. Along with other substances, thionyl chloride and phosphorus oxychloride are used as a halogenating reagent. Thionyl chloride is preferred for the subsequent reaction. This reaction is preferably carried out for 1-10 hours at room temperature to the boiling point of the solvent used.

Reaction I serves to obtain methyl compound II by reducing the halogenated compound Ih. As the reducing agent, metal hydrides (e.g., organotin hydride), metal hydride complexes (e.g., sodium aluminum hydride or sodium borohydride), metals and their salts (e.g., zinc, copper, sodium or lithium) are used. In the case of the use of metal hydride (for example, Ph ₃ SnH or Bu ₃ SnH), this reaction is preferably carried out in an aromatic hydrocarbon solvent (for example, benzene or toluene) using 1-3 times the number of moles of tin hydride compounds for 3-10 hours at boiling point of the solvent used. Although this reaction proceeds quickly using iodide or bromide, it is preferable to add peroxide (for example, perbenzoic acid) or azobisisobutyronitrile (AIBN) to this reaction system in order to accelerate this reaction in the case of the use of a chlorine compound.

 The reaction j serves to obtain a substituted compound Ik as a result of the substitution reaction of the halogen-containing compound Ih using a nucleophilic reagent in an organic solvent. Examples of the organic solvent include alcohols (e.g. methanol, ethanol, propanol and butanol), ethers (e.g. tetrahydrofuran and dioxane), halogenated hydrocarbons (e.g. dichloromethane, chloroform and dichloroethane), acetonitrile and dimethylformamide. The solvent used is preferably selected depending on the nucleophilic reagent used. Examples of the nucleophilic reagent include alcohols such as methanol, ethanol, etc. thiols such as methyl mercaptan, etc. amines such as alkylamine, aralkylamine, etc. and cyanides, such as potassium cyanide, etc.

 This reaction is preferably carried out in the presence of an appropriate base (for example, potassium carbonate, sodium carbonate, sodium hydride, sodium alcoholate, etc.).

The preferred reaction time is usually 1-10 hours at temperatures from ice-cooling temperature ^to 50 ° C, but these conditions vary depending on the combination of the reagent and the solvent.

 Reaction k serves to convert nitrile Ik to Il ester.

Typically and preferably a nitrile Ik is heated at temperatures from 5 ^{° C} to the reflux temperature of the solvent for 3-20 hours in an alcohol (e.g., methanol, ethanol, propanol, butanol, etc.) containing a 3-10 fold excess moles hydrogen chloride gas. Then the used alcohol enters as a solvent, as well as a reaction reagent. Although an iminoether is formed as an intermediate during the reaction, it is preferable to obtain an ester compound without isolating the intermediate.

 Reaction l serves to prepare the Im ester by esterification of If carboxylic acid with alcohol.

 This reaction is usually carried out using a reactive alcohol (e.g., methanol, ethanol, propanol, or butanol) in the presence of an acid catalyst. Examples of the catalyst include a mineral acid, such as hydrochloric acid and sulfuric acid, or an organic acid, such as para-toluenesulfonic acid.

 This reaction is preferably carried out for 5-20 hours at the boiling point of the solvent.

 The reaction products obtained as a result of reactions with a l can be easily isolated using known methods of separation and purification, for example, by column chromatography and recrystallization.

 From these compounds I, salts can be prepared in a conventional manner using a physiologically acceptable acid or base, for example, salts of inorganic acids such as hydrochloride, sulfate and nitrate, salts of organic acids such as acetate, oxalate, citrate and maleate, alkali metal salts such as sodium salt and calcium salt.

 Among these compounds, the starting compounds II, III, IV and V can be synthesized, for example, using the methods described in the following literature, or using methods analogous to them.

 1) Preston P.N. Chemistry of Heterocyclic Compounds, vol. 40 / Ed. P.N. Preston. Tone Wilsi and Sons, New York (1981), p. 1-286.

 2) Hunger A. Kebrl J. Rossi A. and Hotman K. Helv, Chem. Act, 43, 1032 (1960).

 3) R.K.de Selms, J.Org.Kem. 27, 2163 (1962).

 4) Casey A.F. and J. Reed, J. Kem.sos, (C), 1966, 1511.

 5) Met-Con O. Suchitski G. and Sutton M.E. J, by whom. sos, (C), 1968, 1722.

 6) Sazhenov A.A. Kadyrov C.Sh. and Kurbanov P. Chemistry of heterocyclic compounds, 1972, p. 641

 7) Vinot N. Bull.sos, chem. fr. 1966, 3989.

 8) Partridge M.V. and Ternev G.A. J.Kem.sos. 1958, 2086.

 9) Lil R.E. and Lamattina J.L. J. org. 40, 438 (1975).

 10) Dandegaonker S.G. and Revankar K.R. J. Karnatak University. 6, 25 (1961) (see CA, 59, 10023).

11) Kanaoka J. Enemitsu O. Tanizawa K and Ban J. Kem.pharm.bul. 12, 773 (1964)
12) Preston J. Devinter V.F. and Hofferbert V.L. Jr., J. heterocycle, by whom. 6, 119 (1969).

 13) Bishop B.K. Jones A.S. and Tatlow J.K. J. by whom. SOS. 1964, 3076.

 14) Depurter G.J.J. Van Mierlo, M.J. Liber and J.M. Nis. Bel, 595, 327, March 23, 1961 (see CA, 58, 9085 a (1964)).

 15) G.J.J.D. Luzen and E.F. Godefroy, J. org. 38, 3495 (1973).

 16) Suzuki N. Yamabayashi T. and Izawa I. Bul. by whom. coc. Japan, 49, 353 (1976).

 17) W.J. Greerda, R.E. Jones, J.Gal and M.Sletzinger, J.org.Kem. 30, 259 (1955).

 18) I. Itaya, Yakugaku Zashi, 82, 1 (1965).

 19) I. Ganea and R. Taranu, Stud. Univ. Babes-Volyy, Ser.kem. 1966, 95 (see CA, 67, 32648 (1967)).

 20) Gerchel D. Fisher G and Crasht M. Ann, by whom. 162 (1952).

 21) Kokhlov N.S. and Tovshtein M.N. News of the Academy of Sciences of the Byelorussian SSR, Ser.chem.nauk, 1967, 89 (see SA, 69, 49507r).

 22) J.B. Wright, Kem.rev. 48, 397 (1951).

 The starting compound IV can be easily obtained by alkylation of compound VI synthesized, for example, using the method described in the article by K. Seno, S. Nagishita, T. Sato and K. Kuriyama, J. Kem.sos. Perkin trans, 1, 1984, 2013, or by using a similar method, or as a result of the implementation in relation to compound VI of the reaction similar to reaction a and / or a similar reaction (for example, the reaction represented by the following scheme / m //.

 The starting compounds v can be obtained by performing the reaction represented by the following scheme n, or a similar reaction.

 The starting compound XIV and XV can be obtained by performing the reaction represented by the following Scheme o, or a similar reaction.

в которой A, R₁, R₂, R₃, X и n имеют указанные выше значения, а W представляет атом галогена.Reaction m

in which A, R ₁ , R ₂ , R ₃ , X and n are as defined above, and W represents a halogen atom.

в которой A, R₂, R₃ и Х имеют указанные выше значения, а W представляет атом галогена.Reaction n

in which A, R ₂ , R ₃ and X have the above meanings, and W represents a halogen atom.

в которой A, R₁, R₂, R₃, R₅ и Х имеют указанные выше значения, R₅ представляет сложный эфир карбоновой кислоты, цианогруппу или вариантно защищенный тетразолил, а Z представляет -О-, -NH- или -S-.Reaction about

in which A, R ₁ , R ₂ , R ₃ , R ₅ and X are as defined above, R ₅ is a carboxylic acid ester, a cyano group or optionally protected tetrazolyl, and Z is —O—, —NH— or —S— .

 Reaction m serves to produce N-alkyl compound IV by alkylation of compound VI using a method similar to that used to carry out reaction a.

 When carrying out the reaction n, an acid azide IX, which is obtained by reacting a derivative of o-nitrobenzoate VII with a halogenating reagent (e.g. thionyl chloride, phosphorus oxychloride, etc.) to form acid chloride VIII and subsequent reaction with an azide compound (e.g. sodium azide, etc.) can be easily converted to isocyanate X, and carbamic acid ester XI is obtained in high yield by heating isocyanate X and tert-butanol. On the other hand, carbamic acid ester XI is prepared by heating a mixture of benzoate VII derivative and diphenylphosphoryl azide (DPPA) in tert-butanol. The diamine compound V is obtained in high yield by alkylating the resulting carbamic acid ester XI according to a method similar to that used for the reaction m to form compound XII, followed by deprotection and reaction with a reducing agent (for example, a skeletal nickel hydrogenation catalyst) , tin tetrachloride, a mixture of iron and hydrochloric acid, a mixture of hydrazine and iron chloride (3), etc.).

 When performing the reaction on the benzimidazole XIV derivative in high yield, it is obtained by heating the diamino compound V and the acid chloride (e.g., chloroacetic acid chloride, 2-chloropropionic acid chloride, etc.) in the presence of a base (e.g. triethylamine, pyridine, etc.). ) with the formation of a diacylamino compound, after which the diacylamino compound and acid are heated (for example, a mixture of hydrochloric acid and ethanol, etc.), and the substituted compound XV is obtained in a high yield as a result of the interaction of chlorine Ida XIV with various nucleophilic reagents (for example, sodium methylate, sodium ethylate, methylamine, ethylamine, sodium thiomethylate, sodium thioethylate, etc.). The target compound I can be obtained by performing in relation to the obtained compound XV of reaction b, c or a similar reaction.

 Thus obtained compounds I and their salts are less toxic, well inhibit the vasoconstrictor and hypertensive effects of angiotensin II, cause a hypotensive effect in animals, in particular mammals (for example, humans, dogs, rabbits, rats, etc.), therefore they are useful as therapeutic agents not only for treating hypertension, but also for treating cardiovascular diseases such as heart failure and cerebral hemorrhage. Compounds I and their salts, when used as the medicines mentioned above, can be used orally or non-orally in pure form or in dosage forms such as powders, granules, tablets, capsules, injectable solutions, etc. resulting from mixing with appropriate pharmaceutically acceptable carriers, excipients or diluents.

 The dose varies depending on diseases, symptoms, objects of treatment and methods of administration, while it is desirable that a daily dose of 1-50 mg for oral administration or 1-30 mg for intravenous administration is divided into 2-3 doses if this is used compounds as a treatment for hypertension in adults.

 Next will be given a more specific consideration of the present invention with the use of the following examples of compositions, working examples, experimental examples and control examples, but they should not be construed as limiting the invention.

The following are examples of abbreviations used in this description of the invention:
Me-methyl; Et-ethyl; Pr-propyl; Bu-butyl; Pen-pentyl; Tet-tetrazolyl; THF-tetrahydrofuran; DMF-dimethylformamide; Ph-phenyl; AC acetyl.

 Examples of formulations.

 When using compound I according to the invention as a therapeutic agent for the treatment of diseases associated with circulatory disorders, such as hypertension, heart failure, cerebral hemorrhage, etc. it may be part of the following recipes.

1. Capsules, mg
(1) 2-Butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl]
benzimidazole-7-carboxylic acid 10
(2) Lactose 90
(3) Fine-crystalline cellulose 70
(4) Magnesium Stearate 10
_________
One capsule 180
Components (1), (2), (3) and half of the component (4) are mixed and granulated. The remainder of component (4) is added to these granules. Gelatin capsules are filled with this composition.

2. Tablets, mg (1) 2-Butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl]
benzimidazole-7- carboxylic acid 10 (2) Lactose 35 (3) Corn starch 150 (4) Fine crystalline cellulose 30 (5) Magnesium stearate 5
________ One tablet 230
Components (1), (2), (3), two-thirds of component (4) and half of component (5) are mixed and granulated. The remaining parts of components (4) and (5) are added to these granules, followed by compression of these granules.

3. Compositions for injection, mg (1) Disodium salt of 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphe-
nil-4-yl] methyl] benzimidazole-7-carboxylic acid 10 (2) Inositol 100 (3) Benzyl alcohol 20
____________ One ampoule 130
Components (1), (2) and (3) are dissolved in distilled water for injection to achieve a total volume of 2 ml, and the ampoule is filled with this solution. The whole process is carried out under sterile conditions.

4. Capsules, mg (1) 1- (Cyclohexyloxycarbonyloxy) -ethyl ether
2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] ben-
zimidazole-7-carboxylic acid 10 (2) Lactose 90 (3) Fine crystalline cellulose 70 (4) Magnesium stearate 10
____________ One capsule 180
Components (1), (2), (3) and half of the component (4) are mixed and granulated. The remainder of component (4) is added to these granules. Gelatin capsules are filled with this composition.

5. Tablets, mg (1) 1- (Cyclohexyloxycarbonyloxy) ethyl
2-butyl-1 - [[2'-1H-tetrazol-5-yl) biphenyl-4- ester
il] methyl] benzimidazole-7-carboxylic acid 10 (2) Lactose 35 (3) Corn starch 150 (4) Fine crystalline cellulose 30 (5) Magnesium stearate 5
____________ One tablet 230
Components (1), (2), (3), two-thirds of component (4) and half of component (5) are mixed and granulated. The remaining parts of components (4) and (5) are added to these granules, followed by pressing of said granules.

6. Capsules, mg (1) Pivaloyloxymethyl ether 2-butyl-1 - [[2 '- (1H-
tetrazol-5-yl) biphenyl-4-yl] methyl]
benzimidazole-7-carboxylic acid 10 (2) Lactose 90 (3) Fine crystalline cellulose 70 (4) Magnesium stearate 10
____________ One capsule 180
Components (1), (2), (3) and half of the component (4) are mixed and granulated. The remainder of component (4) is added to these granules. Gelatin capsules are filled with this composition.

7. Tablets, mg (1) Pivaloyloxymethyl ether 2-butyl-1 - [[2 '- (1H-
tetrazol-5-yl) biphenyl-4-yl] methyl]
benzimidazole-7-carboxylic acid 10 (2) Lactose 35 (3) Corn starch 150 (4) Fine crystalline cellulose 30 (5) Magnesium stearate 5
____________ One tablet 130
Components (1), (2), (3), two-thirds of component (4) and half of component (5) are mixed and granulated. The remaining parts of components (4) and (5) are added to these granules, followed by pressing of said granules.

 CONTROL PRI me R 1. 2-Butyl-5-methoxybenzimidazole.

Triethylamine (5.7 g) was added to a solution of 4-methoxy-O-phenylenediamine (4.4 g) and the hydrochloride salt of valeroimide acid ethyl ester (4.6 g) in ethanol (50 ml), after which the mixture was stirred for 2 5 hours at room temperature. After removal of the solvent by evaporation, the resulting residue was dissolved in ethyl acetate and water, the organic layer was washed with water, dried and concentrated. The concentrate was purified by silica gel column chromatography, whereby a crystalline product was obtained. Recrystallization from isopropyl ether allowed to obtain needles (2.7 g, 53%), melting point 95-96 ^about C.

Elemental analysis for C ₁₂ H ₁₆ N ₂ O
Calculated, C 70.50.

 Found, C, 70.68; H 7.95; N, 13.72.

Spectrum 1 ^H- NMR (CDCl ₃ ) δ: 0.93 (3H, t); 1.2-2.0 (4H, m); 2.89 (2H, t.); 3.81 (3H, s); 6.84 (1H, q); 7.02 (1H, d); 7.42 (1H, d.).

 Similarly to control example 1, the following compounds were synthesized.

 CONTROL PRI me R 2. 2-Butyl-5-chlorobenzimidazole.

Colorless needles, melting point 149-150 ^о С, 78% yield
Elemental analysis for C ₁₁ H ₁₃ ClN ₂ :
Calculated, C 63.31, H 6.28; N 13.42;
Found, C, 63.35; H, 6.46; N, 13.30.

Spectrum 1 ^H- NMR (CDCl ₃ ) δ: 0.90 (3H, t); 1.20-1.60 (2H, m); 1.67-2.00 (2H, m); 1.67-2.00 (2H, m); 2.92 (2H, t); 7.17 (1H, m); 7.38-7.52 (2H, m).

 CONTROL PRI me R 3. 2-Butyl-5-nitrobenzimidazole.

Colorless crystals, melting point 140-141 ^о С, yield 77%
CONTROL PRI me R 4. 2-Propylbenzimidazole.

 A mixture of o-phenylbenzimidazole.

A mixture of o-phenylenediamine (2.2 g) in butyric anhydride (4.7g) was stirred for 4 hours at 110 ^C. To this reaction mixture was added water, and then extracted with ethyl acetate. The organic layer was washed with an aqueous solution of sodium bicarbonate, diluted with hydrochloric acid and water, and then dried. The solvent is evaporated to dryness, and the residue is heated under reflux in 3 N. Hcl solution (35 ml) for 1.5 hours. The reaction mixture was made basic with 6 N NaOH solution. The crystals are recrystallized from a mixture of ethyl acetate and hexane to form colorless plates (0.9 g, 38%), melting point 160-162 ^about C.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.00 (3H, t); 1.88 (2H, sextet (hexaplet)); 2.91 (2H, t); 2.91 (2H, t.); 7.10-7.35 (2H, m.); 7.45-7.70 (2H, m.); 8.30 (1H, broad singlet).

 CONTROL PRI me R 5. 2-Pentylbenzimidazole.

To a solution of O-phenylenediamine (2.2 g) and triethylamine (2.0 g) in methylene chloride (20 ml), caproyl chloride (2.3 g) was added dropwise with stirring under ice cooling. This mixture was stirred for 3 hours at room temperature, washed with saturated aqueous sodium bicarbonate and water, and then dried. The solvent was evaporated. 3N was added to the residue. HCl solution, after which this mixture is heated under reflux for 1.5 hours. The reaction mixture is made basic using 6 N. NaOH solution. The precipitating crystals are recrystallized from a mixture of ethyl acetate and hexane to form colorless needles (1.5 g, 47%), melting point 161-162 ^about C.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.86 (3H, t); 1.1-1.6 (4H, m); 1.7-2.0 (2H, m); 2.92 (2H, t.); 7.1-7.3 (3H, m.); 7.5-7.7 (2H, m.).

 CONTROL PRI me R 6. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole.

 To a solution of 2-butylbenzimidazole (0.87 g) in dimethylformamide (DMF) (5 ml) was added sodium hydride (60% oil, 0.14 g) under ice-cooling, after which the mixture was stirred for 10 minutes. To the resulting mixture was added 4- (2-cyanophenyl) benzyl chloride (1.1 g) and stirred for 1.5 hours. Water was added to the reaction mixture, and then it was extracted with ethyl acetate. The extract was washed with water and concentrated under reduced pressure.

 The concentrate was purified by silica gel column chromatography to give a colorless oil (1.8 g, quantification).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.90 (3H, t); 1.2-1.6 (2H, m.); 1.65-2.00 (2H, m.); 2.85 (2H, t.); 5.37 (2H, s.); 7.0-7.9 (12H, m.).

 The following compounds (control examples 7-16) were obtained in accordance with the procedure described in control example 6.

 CONTROL PRI me R 7. 2-Butyl- [(2'-cyanobiphenyl-4-yl) methyl] -6-methoxybenzimidazole.

 Oil (yield 48%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.93 (3H, t); 1.14-1.53 (2H, m.); 1.76-1.91 (2H, m.); 2.83 (2H, t.); 3.81 (3H, s.); 5.37 (2H, s.); 6.70 (1H, d.); 6.89 (1H, doublet of doublets); 7.17 (2H, d.); 7.41-7.53 (4H, m.); 7.61-7.68 (2H, m.); 7.77 (1H, doublet of doublets).

Infrared spectrum (pure), cm ^-1 : 2220, 1620, 1595, 1520, 1485, 1460, 1415, 1350, 1275, 1260, 1260, 1215, 1175, 1135, 1105, 1025, 930, 815, 765.

 CONTROL PRI me R 8. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -5-methoxybenzimidazole.

 Oil (44% yield).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.93 (3H, t); 1.35-1.53 (2H, m.); 1.76-1.92 (2H, m.); 2.85 (2H, t.); 3.86 (3H, s.); 5.38 (2H, s.); 6.86 (1H, doublet of doublets); 7.11 (1H, d.); 7.15 (2H, d.); 7.29 (1H, d.); 7.41-7.53 (3H, m.); 7.64 (1H, double triplet); 7.77 (1H, doublet of doublets).

Infrared spectrum (pure), cm ^-1 : 2220, 1620, 1595, 1485, 1440, 1415, 1345, 1275, 1200, 1160, 1030, 835, 800, 765.

 CONTROL PRI me R 9. 2-Butyl-5-chloro-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole.

 Oil (yield 48%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.94 (3H, t); 1.35-1.54 (2H, m.); 1.77-1.92 (2H, m.); 2.87 (2H, t.); 5.40 (2H, s.); 5.40 (2H, s.); 7.12-7.27 (4H, m.); 7.65 (1H, q); 7.75-7.80 (2H, m.).

Infrared spectrum (pure), cm ^-1 : 2220, 1510, 1460, 1400, 760.

 Con tern Example 10. 2-Butyl-6-chloro-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole.

Melting point 124-125 ^about C (yield 35%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.94 (3H, t); 1.35-1.54 (2H, m.); 1.77-1.92 (2H, m.); 2.85 (2H, t.); 5.37 (2H, s.); 7.14 (2H, d.); 7.20-7.25 (2H, m.); 7.41-7.55 (2H, m.); 7.61-7.70 (2H, m.); 7.77 (1H, d.).

Infrared spectrum (KBr), cm ^-1 : 2220, 1620, 1595, 1485, 1440, 1415, 1345, 1200, 1160, 1030, 835, 765.

 CONTROL PRI me R 11. 2-Butyl-1 - [(2'cyanobiphenyl-4-yl) methyl] -5-nitrobenzimidazole.

 Oil (yield 45%).

 CONTROL PRI me R 12. 2-Butyl-1- (2'-cyanobiphenyl-4-yl) methyl-6-nitrobenzimidazole.

 Oil (yield 43%).

 CONTROL PRI me R 13. 1 - [(2'-Cyanobiphenyl-4-yl) methyl] -2-propylbenzimidazole.

 Oil (quantitative yield).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 1.04 (3H, t); 1.82-2.00 (2H, m.); 2.86 (2H, t.); 5.42 (2H, s.); 7.15 (2H, d.); 7.21-7.29 (3H, m.); 7.40-7.53 (2H, m.); 7.59-7.68 (1H, m.); 7.73-7.81 (2H, m.).

Infrared spectrum (pure) cm ^-1 : 2220, 1510, 1480, 1455, 1410, 760, 740.

 CONTROL EXAMPLE 14. 1 - [(2'-Cyanobiphenyl-4-yl) methyl] -2-pentylbenzimidazole.

 Oil (quantitative yield).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.88 (3H, t); 1.23-1.44 (4H, m.); 1.80-1.95 (2H, m.); 2.87 (2H, t.); 5.43 (2H, s.); 7.16 (2H, d.); 7.21-7.29 (3H, m.); 7.41-7.53 (4H, m.); 7.60-7.68 (1H, m.); 7.74-7.82 (2H, m.).

Infrared spectrum (pure), cm ^-1 : 2220, 1510, 1455, 1410, 760, 740.

 CONTROL PRI me R 15. 1 - [(2'-Cyanobiphenyl-4-) yl-methyl] benzimidazole.

 Oil (quantitative yield).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 5.44 (2H, s.); 7.26-7.34 (4H, m.); 7.41-7.55 (2H, m.); 7.60-7.68 (1H, m.); 7.76 (1H, doublet of doublets); 7.83-7.87 (1H, m.); 8.01 (1H, s.).

Infrared spectrum (pure), cm ^-1 : 2220, 1500, 1480, 1460, 1440, 1365, 1285, 760, 740.

 CONTENTION EXAMPLE 16. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole.

 Oil (quantitative yield).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.90 (3H, t); 1.2-1.6 (2H, m.); 1.65-2.00 (2H, m.); 2.85 (2H, t.); 5.37 (2H, s.); 7.0-7.9 (12H, m.).

 CONTROL EXAMPLE 17. 2-Butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole.

 2-Butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole.

A mixture of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole (1.8 g), sodium azide (0.98 g) and ammonium chloride (0.80 g) was stirred in dimethylformamide (6 ml) at ¹¹⁰ ° C for 5 days, adding to the reaction system sodium azide (1.6 g), ammonium chloride (1.3 g) and dimethylformamide (5 ml). Water and ethyl acetate were added to the reaction mixture, and the precipitated crystals were collected by filtration. The organic layer of the filtrate was washed with water, dried and concentrated under reduced pressure to give crude crystals. These crystals are combined with previously obtained crystals, and then recrystallized from a mixture of ethyl acetate and methanol, which allowed to obtain colorless prisms (0.82 g, 41%), melting point 235-236 ^about C.

Elemental analysis for C ₂₅ H ₂₆ N ₆ :
Calculated, C 73.51; H 5.92; N, 20.57.

 Found, C, 73.42; H 5.90; N, 20.87.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.87 (3H, t.); 1.26-1.45 (2H, m.); 1.62-1.77 (2H, m.); 2.82 (2H, t.); 5.49 (2H, s.); 7.05 (2H, s.); 7.13-7.22 (2H, m.); 7.46-7.71 (6H, m.).

Infrared spectrum (KBr), cm ^-1 : 1510, 1460, 1415, 775, 760, 745.

 The following compounds were obtained in accordance with the procedure described in control example 17.

 CONNECTION PRI me R 18. 2-Butyl-5-methoxy-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl ] benzimidazole.

Melting point 146-149 ^about With (decomposition).

Elemental analysis for C ₂₆ H ₂₆ N ₆ O · 2/5 H ₂ O.

 Calculated, C 70.06; H, 6.06; N, 18.85.

 Found, C, 70.27; H 6.03; N, 18.42.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.87 (3H, t.); 1.25-1.44 (2H, m.); 1.60-1.75 (2H, m.); 2.78 (2H, t.); 3.77 (3H, s.); 5.45 (2H, s.); 6.80 (1H, q); 7.01 (2H, d.); 7.06 (2H, d.); 7.13 (1H, d.); 7.35 (2H, d.); 7.47-7.70 (2H, m.).

Infrared spectrum (KBr), cm ^-1 : 1490, 1450, 1440, 1195, 1155, 1020, 825, 755.

 CONNECTION PRI me R 19. 2-Butyl-6-methoxy-1 - [[2 '- (1H-tetrazol-5-yl) -biphenyl-4-yl] methyl] benzimidazole.

Melting point 243-244 ^about C (decomposition).

Elemental analysis for C ₂₆ H ₂₆ N ₆ O.

 Calculated, C 71.21; H 5.98; N, 19.16.

 Found, C, 70.98; H 5.96; N, 19.41.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.86 (3H, t); 1.24-1.43 (2H, m.); 1.58-1.73 (2H, m.); 2.75 (2H, t.); 3.75 (3H, s.); 5.45 (2H, s.); 6.78 (1H, q); 7.05 (5H, m.); 7.43-7.70 (5H, m.).

Infrared spectrum (KBr), cm ^-1 : 1615, 1490, 1450, 1260, 1220, 1020, 825, 810, 745.

 CONNECTION PRI me R 20. 2-Butyl-5-chloro-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl ] benzimidazole.

Melting point 249-250 ^about With (decomposition).

Elemental analysis for C ₂₅ H ₂₃ ClN ₆ · 1/2 H ₂ O.

 Calculated, C 66.44; H 5.35; N, 18.59.

 Found, C, 66.55; H 5.13; N, 18.37.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.87 (3H, t.); 1.26-1.44 (2H, m.); 1.61-1.76 (2H, m.); 2.81 (2H, t.); 5.50 (2H, s.); 6.99-7.09 (4H, m.); 7.20 (1H, q); 7.47-7.70 (7H, m.).

Infrared spectrum (KBr), cm ^-1 : 1500, 1450, 1410, 1000, 785, 760.

 CONTROL PRI me R 21. 2-Butyl-6-chloro-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl ] benzimidazole.

Melting point 216-217 ^about C.

Elemental analysis for C ₂₅ H ₂₃ ClN ₆ :
Calculated, C 67.79; H 5.23; N, 18.97.

 Found, C, 67.41; H 5.19; N, 19.02.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.86 (3H, t); 1.25-1.43 (2H, m.); 1.60-1.75 (2H, m.); 2.79 (2H, t.); 5.51 (2H, s.); 7.01 (2H, d.); 7.08 (2H, d.); 7.18 (1H, q); 7.49-7.72 (6H, m.).

Infrared spectrum (KBr), cm ^-1 : 1460, 1410, 755.

 CONTENTION EXAMPLE 22. 1 - [[2'- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole.

Yield 51%, melting point 238-239 ^о С.

Elemental analysis for C ₂₁ H ₁₆ N ₆ · 1/5 H ₂ O.

 Calculated, C 70.85; H 4.64; N, 23.61.

 Found, C, 70.75; H 4.40; N, 23.41.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 5.51 (2H, s.); 7.07 (2H, d.); 7.19-7.28 (4H, m.); 7.49-7.71 (6H, m.); 8.42 (1H, s.).

Infrared spectrum (KBr), cm ^-1 : 1505, 1460, 1375, 1290, 1265, 1230, 1195, 1145, 1035, 965, 945, 820, 775, 760, 750, 740.

 CONSTRUCTION EXAMPLE 23. 2-Propyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole .

Yield 70% Melting point 239-240 ^{° C} (decomposition).

Elemental analysis for C ₂₄ H ₂₂ N ₆ · 1/2 MeOH · 3/5 H ₂ O
Calculated, C 69.85; H 6.03; N, 19.95.

 Found, C, 69.88; H 6.01; N, 19.79.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.96 (3H, t); 1.67-1.85 (2H, m.); 3.05 (2H, t.); 5.68 (2H, s.); 7.09 (2H, d.); 7.17 (2H, d.); 7.40-7.77 (8H, m.).

Infrared spectrum (KBr), cm ^-1 : 1505, 1480, 1460, 1415, 1405, 760, 745.

 CONTENTION EXAMPLE 24. 2-Pentyl-1 [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole.

Yield 41%, melting point 208-209 ^о С.

Elemental analysis for C ₂₆ H ₂₆ N ₆ :
Calculated, C 73.91; H, 6.20; N, 19.89.

 Found, C, 73.67; H, 6.19; N, 20.00.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.84 (3H, t.); 1.27-1.34 (4H, m.); 1.64-1.78 (2H, m.); 2.81 (2H, t.); 5.49 (2H, s.); 7.04 (4H, s.); 7.12-7.20 (2H, m.); 7.46-7.69 (6H, m.).

Infrared spectrum (KBr), cm ^-1 : 1510, 1460, 1410, 745.

 CONSTRUCTION FOR EXAMPLE 25. Methyl ester of 2- [4- (2-butylbenzimidazol-1-yl) methylphenyl] benzoic acid.

 To a solution of 2-butylbenzimidazole (0.52 g) in dimethylformamide (4 ml) was added sodium hydride (60% oil, 0.13 g) under ice-cooling, after which the mixture was stirred for 20 minutes. To the resulting mixture was added 2- (4-bromomethylphenyl) benzoic acid methyl ester (1.0 g) and stirred for 1.5 hours at room temperature. Water was added to this mixture, and then extraction was performed with ethyl acetate. The solvent is evaporated to dryness, which allows to obtain an oily residue. This oil was purified by silica gel column chromatography to give a colorless oil (1.2 g, quantification).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.92 (3H, t); 1.25-2.00 (4H, m.); 2.87 (2H, t.); 3.60 (3H, s.); 5.36 (2H, s.); 7.05 (2H, d.); 7.15-7.60 (8H, m.); 7.65-7.9 (2H, m).

Infrared spectrum (pure), cm ^-1 : 1725, 1455, 1405, 1280, 1245, 780, 755, 740.

 CONTROL EXAMPLE 26. 2- [4- (2-Butylbenzimidazol-1-yl) methylphenyl] benzoic acid.

 2- [4- (2-Butylbenzimidazol-1-yl) methylphenyl] benzoic acid methyl ester (1.2 g) was heated under reflux in a mixture of 1N. NaOH solution (4.5 ml) and methanol (10 ml for 3 hours) The reaction mixture was concentrated, the concentrate was dissolved in water, washed with ether and then acidified with 1N HCl, resulting in crystals. These crystals were collected by filtration and recrystallized from a mixture of ethyl acetate and methanol to give colorless crystals (0.64 g, 53%).

Elemental analysis for C ₂₅ H ₂₄ N ₂ C ₂ .

 Calculated, C 78.10; H, 6.29; N, 7.29.

 Found, C, 77.99; H 6.36; N, 7.22.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.63 (3H, t); 0.99-1.17 (2H, m.); 1.34-1.49 (2H, m.); 2.62 (2H, t.); 5.32 (2H, s.); 7.04 (2H, d.); 7.18-7.55 (8H, m.); 7.66 (1H, doublet of doublets); 7.92 (1H, doublet of doublets).

Infrared spectrum (KBr), cm ^-1 : 1690, 1610, 1600, 1515, 1465, 1420, 1300, 1250, 1140, 1090, 1005, 820, 765, 750.

 CONTROL PRI me R 27. Methyl ether-2-butylbenzimidazole-4-carboxylic acid.

3-nitro-2-N-valerylaminobenzoic acid methyl ester (2.8 g) was added to a mixture of concentrated HCl (5.3 ml) and methanol (35 ml), after which iron powder (1.7 g) was added in portions. ), produce stirring at room temperature. The resulting mixture was heated under reflux for 8 hours. The insoluble material was filtered off and the filtrate was concentrated. Water and ethyl acetate were added to the concentrate. The aqueous layer is made basic using 6 N. NaOH solution and then extracted with ethyl acetate. The organic layers are combined, washed with water and dried. The solvent was evaporated, and the residue was purified by silica gel column chromatography. The crystals thus obtained were recrystallized from isopropyl ether to give colorless needles (1.6 g, 70%), melting point 97-98 ° ^C.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.93 (3H, t); 1.37-1.56 (2H, m.); 1.80-1.95 (2H, m.); 2.96 (2H, t.); 4.00 (3H, m.); 7.26 (1H, t.); 7.85 (1H, doublet of doublets); 7.91 (1H, d.); 10.13 (1H, broad singlet).

CONTROL PRI me R 28. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-4-carboxylic acid methyl ester
To a solution of 2-butylbenzimidazole-7-carboxylic acid methyl ester (1.5 g) in dimethylformamide (15 ml) was added sodium hydride (60% oil, 0.13 g) under ice-cooling. This mixture was stirred for 20 minutes and then 4- (2-cyanophenyl) benzyl chloride (1.5 g) was added. The resulting mixture was stirred for another 5 hours at room temperature, after which water was added and then extracted with ethyl acetate. The organic layer was washed with water and dried. The solvent was evaporated to dryness, and the residue was purified by silica gel column chromatography to give a pale yellow oil (2.3 g, 82%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.94 (3H, t); 1.37-1.55 (2H, m.); 1.78-1.93 (2H, m.); 2.96 (2H, m.); 4.05 (3H, s.); 5.46 (2H, s.); 7.12 (2H, d.); 7.2 (1H, t.); 7.39-7.52 (5H, m.); 7.64 (1H, double triplet); 7.76 (1H, d.); 7.95 (1H, doublet of doublets).

Infrared spectrum (pure), cm ^-1 : 2220, 1710, 1510, 1480, 1435, 1405, 1350, 1290, 1245, 1215, 1190, 1130, 760.

 CONTROL PRI me R 29. Methyl ether 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole -4- carboxylic acid.

A mixture of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-4-carboxylic acid methyl ester (2.3 g), sodium azide (5.3 g) and ammonium chloride (4.4 g) was stirred in dimethylformamide (20 ml) at 110-120 ^C for 26 hours. to the reaction mixture were added water and ethyl acetate, after which it was acidified with concentrated hydrochloric acid. Precipitated crystals were collected by filtration and recrystallized from methanol to give colorless needles (0.22 g, 9%), melting point 223-224 ^C (decomposition).

Elemental analysis for C ₂₇ H ₂₆ N ₆ O ₂ · 0.3 H ₂ O.

 Calculated, C 68.72; H 5.68; N, 17.81.

 Found, C, 68.69; H 5.68; N, 17.57.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.88 (3H, t.); 1.28-1.47 (2H, m.); 1.60-1.75 (2H, m.); 2.88 (2H, t.); 3.89 (3H, s.); 5.56 (2H, s.); 7.01 (2H, d.); 7.07 (2H, d.); 7.27 (1H, t.); 7.47-7.66 (4H, m.); 7.72-7.77 (2H, m.).

Infrared spectrum (KBr), cm ^-1 : 1710, 1460, 1435, 1420, 1295, 1140, 765.

 CONTROL PRI me R 30. 2-Butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-4 carboxamide.

The reaction is basically the same as in Control Example 29. Water and ethyl acetate are added to the reaction mixture, and then acidified with 6 N HCl solution. Precipitating crystals are collected by filtration. The organic layer was separated from the filtrate, which was washed with water, dried and concentrated to dryness. The residue was purified by silica gel column chromatography. The crystals thus obtained were recrystallized from a mixture of methanol and chloroform to give colorless prisms (0.37 g, 15%), melting point 235-236 ° ^C.

Elemental analysis for C ₂₆ H ₂₅ N ₇ O · 1/2 H ₂ O.

 Calculated, C 67.81; H, 5.69; N, 21.29.

 Found, C, 67.64; H 5.68; N, 21.05.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.89 (3H, t); 1.30-1.48 (2H, m.); 1.65-1.80 (2H, m.); 2.90 (2H, t.); 5.58 (2H, s.); 7.06 (4H, s.); 7.30 (1H, t.); 7.48-7.74 (5H, m.); 7.84 (1H, doublet of doublets); 9.28 (2H, s.).

Infrared spectrum (KBr), cm ^-1 : 1660, 1610, 1565, 1500, 1465, 1420, 1390, 1350, 1255, 1080, 1070, 1015, 885, 800, 775, 750.

 CONTROL PRI me R 31. Methyl ester of 3-nitro-2-valerylaminobenzoic acid.

Smoky nitric acid (7.0 ml) was added dropwise to acetic anhydride (60 ml) under ice-cooling, after which concentrated sulfuric acid (0.2 ml) was added. Then, 2-valerylaminobenzoic acid methyl ester (12 g) was added to this mixture and stirred for 1 h at room temperature. A mixture of water and ice was added to the resulting mixture, and then extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. The concentrate was purified by column chromatography on silica gel, whereby the obtained crude crystals were recrystallized from isopropyl ether gives colorless needles (3.9 g, 28%), melting point 61-62 ° ^C.

Elemental analysis for C ₁₃ H ₁₆ N ₅ O ₅ .

 Calculated, C 55.71; H 5.75; N, 9.99.

 Found, C 55.72; H 5.79; N, 9.83.

Spectrum 1 ^H- NMR (CDCl ₃ ) δ: 0.95 (3H, t); 1.30-1.50 (2H, m.); 1.65-1.80 (2H, m.); 2.46 (2H, t.); 3.97 (3H, s.); 7.30 (1H, t.); 8.10 (1H, doublet of doublets); 8.22 (1H, doublet of doublets).

 CONTENTION EXAMPLE 32. 2- [N- (2'-Cyanobiphenyl-4-yl) methyl-N-valeryl] amino-3-nitrobenzoic acid methyl ester.

A mixture of 3-nitro-2-valerylaminobenzoic acid methyl ester (3.9 g), 4- (2-cyanophenyl) benzyl bromide (3.8 g) and K ₂ CO ₃ (2.1 g) in dimethylformamide (30 ml) stirred for 15 hours at room temperature. Water was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed with water and dried. The solvent was evaporated to dryness, and the residue was purified by silica gel column chromatography. The resulting crude crystals were recrystallized from a mixture of ethyl acetate and hexane to give colorless crystals (5.1g, 78%), melting point 129-130 ° ^C.

Elemental analysis for C ₂₇ H ₂₅ N ₃ O ₅ .

 Calculated, C 68.78; H 5.34; N, 8.91.

 Found, C, 68.84; H 5.43; N, 8.87.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.85 (3H, t); 1.18-1.36 (2H, m.); 1.61-1.76 (2H, m.); 2.08-2.16 (2H, m.); 3.67 (3H, s.); 4.65 (1H, d.); 4.96 (1H, d.); 7.20 (2H, d.); 7.38-7.50 (4H, m.); 7.56-7.68 (2H, m.); 7.75 (1H, d.); 7.98 (1H, doublet of doublets); 8.10 (1H, doublet of doublets).

 CONTENTION EXAMPLE 33. 2-Butyl-1- [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-7-carboxylic acid methyl ester.

To a mixture of 2- [N- (2'-cyanobiphenyl-4-yl) methylvaleryl] amino-3-nitrobenzoic acid methyl ester (5.14 g) in concentrated HCl (4.0 ml) and methanol (10 ml) with stirring iron powder (1.9 g) is added in portions. This mixture is stirred at a temperature of 70-80 ^about C for 3 hours, then the insoluble material is filtered off, and the filtrate is concentrated. Ethyl acetate and saturated aqueous sodium bicarbonate were added to the concentrate. The precipitated insoluble material is filtered off. An aqueous layer was separated from the filtrate, which was extracted with ethyl acetate. The organic layers are combined, dried and concentrated to form a crystalline residue. Recrystallization from ethyl acetate allows to obtain colorless needles (4.15 g, 90%), melting point 123-124 ^about C.

Elemental analysis for C ₂₇ H ₂₅ N ₃ O ₂ .

 Calculated, C 76.57; H 5.95; N, 9.92.

 Found, C, 76.44; H 6.03; N, 9.67.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.96 (3H, t); 1.38-1.57 (2H, m.); 1.82-1.97 (2H, m.); 2.92 (2H, t.); 3.72 (3H, s.); 5.82 (2H, s.); 6.97 (2H, d.); 7.26 (1H, d.); 7.39-7.46 (4H, m.); 7.58-7.66 (2H, m.); 7.75 (1H, doublet of doublets); 7.97 (1H, doublet of doublets).

Infrared spectrum (KBr), cm ^-1 : 2220, 1725, 1480, 1440, 1420, 1400, 1280, 1260, 1195, 1140, 1115, 765, 750, 745.

 The following compounds were obtained in accordance with the procedure described in control example 31.

 CONSTRUCTION EXAMPLE 34. Methyl ester of 2-butyrylamino-3-nitrobenzoic acid.

Melting point 64-65 ^about C.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.03 (3H, t); 1.57-1.97 (2H, m.); 2.43 (2H, t.); 3.97 (3H, s.); 7.20-7.43 (1H, m.); 8.07-8.27 (2H, m.); 10.50 (1H, broad singlet).

Infrared spectrum (nujol), cm ^-1 : 3300, 1725, 1690, 1585, 1535, 1510, 1445, 1355, 1265, 1210, 1115.

 CONTROL PRI me R 35. Methyl ester of 2-hexanoylamino-3-nitrobenzoic acid.

Melting point 74-75 ^about C.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.90 (3H, t); 1.23-1.90 (6H, m.); 2.43 (2H, t.); 3.93 (3H, s.); 7.27 (1H, t.); 8.03-8.27 (2H, m.); 10.30 (1H, broad singlet).

Infrared spectrum (nujol), cm ^-1 : 3320, 1725, 1675, 1635, 1505, 1270.

 The following compounds were obtained basically the same as in control example 32.

 CONTENTION EXAMPLE 36. 2- [N-Butyryl-N- (2'cyanobiphenyl-4-yl) methyl] amino-3-nitrobenzoic acid methyl ester.

Melting point 150-151 ^{° C} (yield 78%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.87 (3H, t); 1.50-1.90 (2H, m.); 2.10 (2H, t.); 3.67 (3H, s.); 4.83 (2H, q); 7.17-7.80 (9H, m.); 7.93-8.17 (2H, m.).

Infrared spectrum (nujol), cm ^-1 : 2220, 1740, 1670, 1530, 1445, 1430, 1390, 1345, 1290, 1280, 1250, 1125, 770.

 CONTENTION EXAMPLE 37. 2- [N- (2'-Cyanobiphenyl-4-yl) methyl-N-hexanoyl] amino-3-nitrobenzoic acid methyl ester.

Melting point 85-86 ^{° C} (yield 75%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.83 (3H, t); 1.07-1.37 (4H, m.); 1.50-1.83 (2H, m,); 2.10 (2H, t.); 3.67 (3H, s.); 4.83 (2H, q); 7.17-7.80 (9H, m.); 7.93-8.17 (2H, m.).

Infrared spectrum (nujol), cm ^-1 : 2220, 1735, 1670, 1530, 1480, 1445, 1430, 1390, 1375, 1345, 1290, 1270, 1260, 1200, 1130, 775.

 The following compounds were obtained basically the same as in control example 33.

 CONTENTION EXAMPLE 38. 1 - [(2'-Cyanobiphenyl-4-yl) methyl] -2-propylbenzimidazole-7-carboxylic acid methyl ester.

Melting point 130-131 ^{° C} (yield 78%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.07 (3H, t); 1.93 (2H, broad singlet); 2.90 (2H, broad singlet); 3.70 (3H, s.); 5.83 (2H, broad singlet); 6.93-8.07 (11H, m.).

Infrared spectrum (nujol), cm ^-1 : 2220, 1710, 1450, 1400, 1290, 1270, 1265, 1200, 1125, 760.

CONNECTIONS PRI me R 39. 1 - [(2'-Cyanobiphenyl-4-yl) methyl] -2-peptide benzimidazole-7-carboxylic acid methyl ester
Melting point 109-110 ^{° C} (yield 75%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.90 (3H, t); 1.17-2.10 (6H, m.); 2.90 (2H, t.); 3.70 (3H, s.); 5.83 (2H, s.); 6.97 (2H, d.); 7.13-8.00 (9H, m.);
Infrared spectrum (nujol), cm ^-1 : 2220, 1710, 1450, 1430, 1280, 1260, 1190, 1120, 750.

 CONNECTION PRI me R 40. Methyl ester of 3-nitro-4-valerylaminobenzoic acid.

Fuming nitric acid (1.4 ml) was added dropwise to acetic anhydride (12 ml) under ice-cooling, after which concentrated sulfuric acid (0.1 ml) was added to this mixture. 4-valerylaminobenzoic acid methyl ester (2.3 g) was added to the stirred mixture under ice cooling and stirred for 1 h. A mixture of water and ice was added to the resulting mixture, the separated crystals were recrystallized from a mixture of ethyl acetate and hexane to give yellow prisms (2, 14 g, 76%), melting point 106-107 ^about C.

Elemental analysis for C ₁₃ H ₁₆ N ₂ O ₅ .

 Calculated, C 55.71; H 5.75; N, 9.99.

 Found, C, 55.84; H 5.80; N, 10.01.

Spectrum 1 ^H- NMR (CDCl ₃ ) δ: 0.98 (3H, t); 1.20-1.60 (2H, m.); 1.70-1.85 (2H, m.); 2.53 (2H, t.); 3.96 (3H, s.); 8.28 (1H, doublet of doublets); 8.91 (1H, d.); 8.96 (1H, d.); 10.60 (1H, broad singlet).

 CONTROL EXAMPLE 41. 4- [N- (2'-Cyanobiphenyl-4-yl) methyl-N-valerylamino] -3-nitrobenzoic acid methyl ester.

A mixture of 4-valerylamino-3-nitrobenzoic acid methyl ester (2.1 g), 4- (2-cyanophenyl) benzyl bromide (2.0 g) and K ₂ CO ₃ (1.1 g) in dimethylformamide (20 ml) stirred for 4 hours at room temperature. Water was added to the reaction mixture and extracted with ethyl acetate, after which the organic layer was washed with water. The resulting solution was dried and concentrated to form a syrup, which was purified by silica gel column chromatography to give a yellow syrup (3.5 g, quantitative determination).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.83 (3H, t); 1.15-1.33 (2H, m.); 1.55-1.70 (2H, m.). 1.99-2.08 (2H, m.); 3.98 (3H, s.); 4.27 (1H, d.); 5.5 (1H, d.); 7.07 (1H, d.); 7.27 (2H, d.); 7.42-7.56 (4H, m.); 7.62-7.70 (1H, m.); 7.77 (1H, d.); 8.19 (1H, q); 8.61 (1H, d.).

Infrared spectrum (pure), cm ^-1 : 2220, 1730, 1610, 1535, 1480, 1435, 1390, 1345, 1285, 1240, 765.

 CONTENTION EXAMPLE 42. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-5-carboxylic acid methyl ester.

4- [N- (2'-cyanobiphenyl-4-yl) methyl-N-valeryl amino] -3-nitrobenzoic acid methyl ester is added to a mixture of concentrated HCl (4.0 ml) and methanol (10 ml) (3, 5 g). To the mixture under stirring was added portionwise the iron powder (1.3 g), stirring was continued for 1 hour at 70-80 ^{° C,} then insoluble material was filtered off, the filtrate was concentrated, dissolved in ethyl acetate, washed with water, dried and concentrated to dryness condition. The resulting syrup was purified by silica gel column chromatography to give a yellow syrup (1.7 g, 53%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.94 (3H, t); 1.45 (2H, sextet); 1.79-1.94 (2H, m.); 2.89 (2H, t.); 3.94 (3H, s.); 5.44 (2H, s.); 7.15 (2H, d.); 7.27 (1H, d.); 7.42-7.54 (4H, m.); 7.65 (1H, double triplet); 7.77 (1H, doublet of doublets); 7.97 (1H, doublet of doublets); 8.50 (1H, doublet of doublets).

Infrared spectrum (pure), cm ^-1 : 2220, 1720, 1615, 1480, 1440, 1400, 1335, 1300, 1280, 1210, 755.

 CONTENTION EXAMPLE 43. Methyl 2-butyl-1- [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole -5-carboxylic acid.

Mixture of 4- [N- (2'-cyanobiphenyl-4-yl) methyl-valerylamino] -3-nitrobenzoic acid methyl ester (1.7 g), sodium azide (3.9 g) and ammonium chloride (3.2 g ) in dimethylformamide (17 ml) was stirred at 115 ^about C for 5 days. Water was added to the reaction mixture and neutralized with a 1N HCl solution, followed by extraction with ethyl acetate. The organic layer was washed with water, dried and concentrated to dryness. The concentrate was purified by silica gel column chromatography, whereby crude crystals were obtained. Recrystallization from ethyl acetate led to the formation of colorless needles (0.77 g, 34%), melting point 134-136 ^about C.

Elemental analysis for C ₂₇ H ₂₆ N ₆ O ₂ · 1/2 H ₂ O.

 Calculated, C 68.19; H 5.72; N, 17.67.

 Found, C, 68.46; H 5.77; N, 17.31.

Spectrum 1 ^H- NMR (100 MHz, CDCl ₃ ) δ: 0.83 (3H, t); 1.18-1.37 (2H, m.); 1.50-1.65 (2H, m.); 2.38 (2H, t.); 3.90 (3H, s.); 5.24 (2H, s.); 6.68 (2H, d.); 6.91 (2H, d.); 7.06 (1H, d.); 7.28-7.33 (1H, m.); 7.54-7.69 (3H, m.); 7.87 (1H, doublet of doublets); 8.00 (1H, doublet of doublets).

Infrared spectrum (KBr), cm ^-1 : 1720, 1615, 1435, 1410, 1340, 1300, 1280, 1220, 1085, 770, 750.

 CONNECTOR EXAMPLE 44. 2-Butyl - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-5-carbon acid.

A mixture of 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-5-carboxylic acid methyl ester (0.3 g) in methanol (3 ml ) containing 2 n. NaOH solution (1 ml), refluxed for 2 hours. The reaction mixture was concentrated to dryness and then diluted with water. The aqueous solution is acidified with 1 N. HCl solution, resulting in the formation of crystals. Recrystallization from a mixture of acetonitrile and methanol allows to obtain colorless crystals (0.23 g, 83%), melting point 180-182 ^about C.

Elemental analysis for C ₂₆ H ₂₄ N ₆ O ₂ .

 Calculated, C 68.16; H 5.49; N, 19.08.

 Found, C, 68.43; H 5.27; N, 18.88.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.88 (3H, t.); 1.28-1.46 (2H, m.); 1.63-1.78 (2H, m.); 2.89 (2H, t.); 5.58 (2H, s.); 7.07 (4E, s.); 7.47-7.70 (5H, m.); 7.86 (1H, doublet of doublets); 8.18 (1H, s.).

 CONNECTION PRI me R 45. Methyl ester of 3-valerylaminobenzoic acid.

To a solution of 3-aminobenzoic acid methyl ester (6.0 g) and triethylamine (4.5 g) in methylene chloride (90 ml), valeryl chloride (4.8 g) was added dropwise with stirring and cooling with ice. This mixture was stirred for 1 hour. The reaction mixture was washed with an aqueous solution of sodium bicarbonate, diluted with hydrochloric acid and water, followed by drying and concentration to dryness. The concentrate is crystallized from a mixture of ethyl acetate and hexane to form colorless prisms (8.1 g, 87%), melting point 101-102 ^about C.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.93 (3H, t); 1.2-1.9 (4H, m.); 2.37 (2H, t.); 3.90 (3H, s.); 7.36 (1H, t.); 7.5 (1H, broad singlet); 7.70-7.95 (2H, m.); 8.03 (1H, t.).

 CONTRACTOR PRI me R 46. Methyl ester of 4-nitro-3-valerylaminobenzoic acid.

 To a solution of 3-valerylaminobenzoic acid methyl ester (2.3 g) in acetic anhydride (12 ml), fuming nitric acid (1.4 ml) was added dropwise while stirring under ice-cooling. One drop of concentrated sulfuric acid was added to this mixture and stirred for 2 hours. A mixture of ice water and water were added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed with an aqueous solution of sodium bicarbonate and water, and then dried. The solvent was evaporated to dryness, and the residue was purified by silica gel column chromatography to give a brown oil (1.0 g, 36%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.96 (3H, t); 1.1-1.9 (4H, m.); 2.51 (2H, t.); 3.96 (3H, s.); 7.80 (1H, doublet of doublets); 8.26 (1H, d.); 9.41 (1H, d.); 10.23 (1H, broad singlet).

Infrared spectrum (pure), cm ^-1 : 3380, 1730, 1615, 1590, 1535, 1500, 1440, 1420, 1325, 1310, 1280, 1250, 1210, 1160, 1160, 1110, 1070, 845, 775, 740.

 CONTENTION EXAMPLE 47. 3- [N- (2'-Cyanobiphenyl-4-yl) methyl-N-valerylamino] -4-nitrobenzoic acid methyl ester.

 A mixture of 4-nitro-3-valerylaminobenzoic acid methyl ester (1.0 g), 4- (2-cyanophenyl) benzyl bromide (0.97 g) and potassium carbonate (0.55 g) in dimethylformamide (10 ml) was stirred in for 2 days at room temperature. Water was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed with water and dried. The solvent was distilled off, and the residue was purified by silica gel column chromatography to give a pale yellow oil (1.24 g, 73%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.84 (3H, t); 1.17-1.30 (2H, m.); 1.56-1.71 (2H, m.); 1.80-2.08 (2H, m.); 3.92 (3H, s.); 4.43 (1H, d.); 5.37 (1H, d.); 7.26 (2H, d.); 7.40-7.51 (4H, m.); 7.60-7.69 (2H, m.); 7.75 (1H, d.); 7.97 (1H, d.); 8.16 (1H, doublet of doublets).

Infrared spectrum (pure), cm ^-1 : 2220, 1735, 1675, 1600, 1580, 1530, 1480, 1435, 1420, 1390, 1350, 1285, 1220, 1200, 1115, 1090, 825, 775, 765.

 CONTENTION EXAMPLE 48. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-6-carboxylic acid methyl ester.

To a solution of 3- [N- (2'-cyanobiphenyl-4-yl) methyl-N-valerylamino] -4-nitrobenzoic acid methyl ester (1.2 g) in methanol (10 ml) containing concentrated HCl (1.3 ml), while stirring at room temperature, iron powder (0.45 g) is added in portions. This mixture was stirred for 3 hours at 70-80 ^C. To the reaction mixture were added water and ethyl acetate, and then remove it basic with aqueous sodium bicarbonate. The precipitates separated after this are filtered. The organic layer separated from the filtrate was washed with water and dried. The solvent was evaporated to dryness, and the residue was purified by silica gel column chromatography. The thus obtained crude crystals were recrystallized from ethyl acetate to give colorless needles (0.5 g, 45%), melting point 166 -167 ^C.

Elemental analysis for C ₂₇ H ₂₅ N ₃ O ₂ .

 Calculated, C 76.57; H 5.95; N, 9.92.

 Found, C 76.39; H 6.05; N, 9.79.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.94 (3H, t); 1.35-1.54 (2H, m.); 1.79-1.94 (2H, m.); 2.88 (2H, t.); 3.92 (3H, s.); 5.47 (2H, s.); 7.14 (2H, d.); 7.40-7.53 (4H, m.); 7.60-7.68 (1H, m.); 7.74-7.80 (2H, m.); 7.96-8.02 (2H, m.).

Infrared spectrum (KBr), cm ^-1 : 2210, 1715, 1620, 1580, 1510, 1480, 1460, 1425, 1410, 1340, 1325, 1280, 1270, 1250, 1230, 1185, 1105, 1080, 770, 760, 745.

 CONSTRUCTION EXAMPLE 49. Methyl 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole -6- carboxylic acid.

A mixture of 2-butyl-1- [2 '- (cyanobiphenyl-4-yl) methyl] benzimidazole-6-carboxylic acid methyl ester (0.5 g), sodium azide and ammonium chloride (1.15 g) in dimethylformamide (5 ml) was stirred at 115 ^about C for 3.5 days. Water was added to the reaction mixture and acidified with 1N HCl, and then extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated to dryness. The concentrate is purified by silica gel column chromatography. The thus obtained crude crystals were recrystallized from a mixture of ethyl acetate and methanol to give colorless crystals (0.23 g, 41%), melting point 224-225 ° ^C.

Elemental analysis for C ₂₇ H ₂₆ N ₆ O ₂ .

 Calculated, C 68.98; H 5.66; N, 17.88.

 Found, C, 68.89; H 5.68; N, 17.66.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.87 (3H, t.); 1.26-1.45 (2H, m.); 1.63-1.78 (2H, m.); 2.85 (2H, t.); 3.85 (3H, s.); 5.62 (2H, s.); 7.00 (2H, d.); 7.07 (2H, d.); 7.48-7.70 (5H, m.); 7.82 (1H, doublet of doublets); 8.14 (1H, s.).

Infrared spectrum (KBr), cm ^-1 : 1725, 1460, 1450, 1435, 1340, 1265, 1235, 775, 760, 745.

 CONTROL PRI me R 50. 2-Butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-6 -carboxylic acid.

A solution of methyl ester of 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-6-carboxylic acid (0.1 g) in methanol (5 ml ) containing 1 N NaOH solution (0.5 ml) was heated under reflux for 5 hours. The solvent was evaporated to dryness and 1 N was added to the residue. HCl solution (0.5 ml) and extracted with chloroform. The organic layer was washed with water, dried and concentrated to dryness. The thus obtained crude crystals were recrystallized from a mixture of methanol and ethyl acetate to give colorless crystals (60 mg, 58%), melting point 258-259 ^C (decomposition).

Elemental analysis for C ₂₆ H ₂₄ N ₆ O ₂ · 1/2 ethyl acetate.

 Calculated, C 67.73; H 5.68; N, 16.92.

 Found, C, 67.79; H 5.50; N, 16.89.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.87 (3H, t.); 1.27-1.45 (2H, m.); 1.63-1.79 (2H, m.); 2.85 (2H, t.); 5.60 (2H, s.); 7.00 (2H, d.); 7.08 (2H, d.); 7.48 (5H, m.); 7.84 (1H, doublet of doublets); 8.11 (1H, s.).

Infrared spectrum (KBr), cm ^-1 : 1730, 1460, 1410, 1335, 1285, 1265, 1225, 780, 760.

 CONNECTIONS PRI me R 51. Methyl ester of 2-amino-5-methylbenzoic acid.

 A mixture of 2-amino-5-methylbenzoic acid (10 g) in methanol (50 ml) containing concentrated sulfuric acid (5.5 ml) was heated under reflux for 19 hours. The solvent was distilled off and the residue was dissolved in water. This solution is neutralized with an aqueous sodium hydroxide solution and then extracted with ethyl acetate. The organic layer was dried and concentrated to give a pale brown oil (8.1 g, 74%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 2.24 (3H, s.); 3.89 (3H, s.); 5.55 (2H, s.); 6.59 (1H, d.); 7.10 (1H, doublet of doublets); 7.68 (1H, d.).

 CONNECTION PRI me R 52. Methyl ester of 5-methyl-2-valerylaminobenzoic acid.

 To a solution of 2-amino-5-methylbenzoic acid methyl ester (8.1 g) and triethylamine (6.0 g) in methylene chloride (50 ml), valeryl chloride (6.5 g) was added dropwise while stirring under ice cooling. The reaction mixture was continued to stir for 2 hours, after which it was washed with an aqueous solution of sodium carbonate, diluted with hydrochloric acid and water, and then dried. The solvent was evaporated to dryness to give a pale brown oil (12.8 g, 99%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.95 (3H, t); 1.2-1.9 (4H, m.); 2.33 (3H, s.); 2.43 (2H, t.); 3.93 (3H, s.); 7.34 (1H, doublet of doublets); 7.82 (1H, d.); 8.62 (1H, d.).

 CONTRACTOR PRI me R 53. 5-Methyl-3-nitro-2-valerylaminobenzoic acid methyl ester.

To a mixture of 5-methyl-2-valerylaminobenzoic acid methyl ester (12.8 g) in acetic anhydride (5.9 g), fuming nitric acid (6.7 ml) was added dropwise under stirring under ice cooling, and stirring was continued. over 3 hours. A mixture of ice-water was added to the reaction mixture and extracted with ethyl acetate. The extract is washed with an aqueous solution of sodium bicarbonate and water, and then dried. The solvent was evaporated to dryness, and the residue was purified by silica gel column chromatography. The crystals thus obtained were recrystallized from isopropyl ether to give colorless crystals (8.5 g, 60%), melting point 59-60 ° ^C.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.94 (3H, t); 1.31-1.50 (2H, m.); 1.63-1.78 (2H, m.); 2.43 (2H, t.); 3.95 (3H, s.); 7.90 (1H, d.); 8.00 (1H, d.); 10.16 (2H, s.).

 CONTENTION EXAMPLE 54. Methyl 2 - [[N- (2'-cyanobiphenyl-4-yl) methyl-N-valeryl] amino] -5-methyl- 3-nitrobenzoic acid.

A mixture of 5-methyl-3-nitro-2-valerylaminobenzoic acid methyl ester (5.89 g), 4- (2-cyanophenyl) benzyl bromide (5.44 g) and sodium carbonate (3.0 g) in dimethylformamide (50 ml) was stirred for 15 hours at 50 ° ^C. to the reaction mixture was added water and extracted with ethyl acetate, and the organic layer was dried. The solvent was distilled off, and the residue was purified by silica gel column chromatography. The crystals thus obtained were recrystallized from a mixture of ethyl acetate and hexane to give colorless crystals (3.1 g, 32%), melting point 141-142 ° ^C.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.85 (3H, t); 1.17-1.36 (2H, m.); 1.60-1.75 (2H, m.); 2.05-2.15 (2H, m.); 2.49 (3H, s.); 3.64 (3H, s.); 4.62 (1H, d.); 4.94 (1H, d.); 7.21 (2H, d.); 7.38-7.50 (4H, m.); 7.59-7.68 (1H, m.); 7.73-7.77 (3H, m.); 7.89 (1H, multiplet).

 CONTENTION EXAMPLE 55. Methyl 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -5-methylbenzimidazole-7-carboxylic acid.

 To a solution of 2 - [[N- (2'-cyanobiphenyl-4-yl) methyl-N-valeryl] amino] -5-methyl-3-nitrobenzoic acid methyl ester (3.1 g) in a mixture of concentrated HCl (4, 4 ml) and methanol (22 ml), iron powder (1.6 g) is added in portions with stirring. This mixture was refluxed for 7 hours. Insoluble materials were filtered off and the filtrate was concentrated. Water was added to the concentrate and extracted with ethyl acetate. The organic layer is washed with an aqueous solution of sodium bicarbonate and water, and then dried. The solvent was distilled off, and the residue was purified by silica gel column chromatography to give a pale brown oil (2.8 g, quantification).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.95 (3H, t); 1.37-1.56 (2H, m.); 1.79-1.94 (2H, m.); 2.47 (3H, s); 2.90 (2H, t.); 3.71 (3H, s.); 5.79 (2H, s.); 6.96 (2H, d.); 7.39-7.46 (5H, m.); 7.58-7.66 (1H, m.); 7.73-7.77 (2H, m.).

Infrared spectrum (pure), cm ^-1 : 2220, 1720, 1520, 1480, 1435, 1410, 1305, 1245, 1215, 1195, 1110, 1040, 780, 760.

 CONTROL PRI me R 56. Ethyl ether of 2-amino-6-methylbenzoic acid.

 This compound was obtained in accordance with the procedure described in control example 51.

 Oil (82% yield).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.34 (3H, t); 2.43 (3H, s.); 4.35 (2H, q); 5.06 (2H, broad singlet); 6.50 (2H, d.); 7.07 (1H, t.).

 CONTROL PRI me R 57. Ethyl ester of 6-methyl-2-valerylaminobenzoic acid.

 This compound was obtained in accordance with the procedure described in control example 52.

Melting point 56-57 ^{° C} (yield 70%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.93 (3H, t); 1.39 (3H, t.); 1.18-1.87 (4H, m.); 2.37 (2H, t.); 2.46 (3H, s.); 4.41 (2H, q); 6.94 (1H, d.); 8.27 (1H, d.); 7.32 (1H, t.); 6.96 (1H, broad singlet).

 CONTROL PRI me R 58. Ethyl ester of 6-methyl-3-nitro-2-valerylaminobenzoic acid.

 This compound was obtained in accordance with the procedure described in control example 53.

Melting point 103-104 ^{° C} (yield 52%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.93 (3H, t); 1.35 (3H, t.); 1.17-1.85 (4H, m.); 2.38 (2H, t.); 2.49 (3H, s.); 4.38 (2H, q); 7.14 (1H, d.); 7.97 (1H, d.).

 CONNECTION PRI me R 59. Ethyl ether 6-methyl-3-nitro-2 - [[2 '- (N-triphenylmethyl-1H-tetrazol-5-yl) biphenyl -4-yl] methyl-N-valeryl] aminobenzoic acid.

 This compound was obtained in accordance with the procedure described in control example 54.

 Oil (80% yield).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.86 (3H, t); 1.34 (3H, t.); 1.20-1.45 (2H, m.); 1.60-1.78 (2H, m.); 2.14 (2H, t.); 2.40 (3H, s.); 4.09 (1H, d.); 5.28 (1H, d.); 4.23-4.42 (2H, m.); 6.81-6.96 (10H, m.); 7.19-7.53 (13H, m.); 7.69 (1H, d.); 7.88 (1H, doublet of doublets).

 CONNECTION PRI me R 60. Methyl ester of 2-amino-5-chlorobenzoic acid.

Concentrated sulfuric acid (12 ml) was added to a solution of 2-amino-5-benzoic acid (25.5 g) in methanol (300 ml). This mixture was refluxed for 24 hours. The reaction mixture was concentrated, water (300 ml) was added, and then neutralized with potassium carbonate. This mixture was extracted with ethyl acetate. The organic layer was washed with water and dried, then the solvent was distilled off, which allowed to obtain crude crystals. Recrystallization from a mixture of isopropyl ether and benzene led to the formation of pale yellow crystals (17.1 g, 63%), melting point 68-70 ^about C.

 CONNECTOR PRI me R 61. Methyl ester of 5-chloro-2-valerylaminobenzoic acid.

To a solution of 2-amino-5-chlorobenzoic acid methyl ester (15 g) and triethylamine (12 ml) in methylene chloride (150 ml), valeryl chloride (10 ml) was added dropwise while stirring under ice-cooling. This mixture was stirred at room temperature for another 2 hours. The reaction mixture was washed with aqueous sodium bicarbonate and then dried. The solvent is distilled off with the formation of pale yellow crystals (13.4 g, 61%), melting point 48-49 ^about C.

 CONNECTOR PRI me R 62. 5-Chloro-3-nitro-2-valerylaminobenzoic acid methyl ester.

To a solution of 5-chloro-2-valerylaminobenzoic acid methyl ester (13.4 g) in acetic anhydride (10 ml), fuming nitric acid was added dropwise, while stirring under ice-cooling. This mixture was stirred for another 1 h at room temperature, and then a mixture of water and ice was added. This mixture is left to stand, resulting in the formation of crystals. Recrystallization from isopropyl ether allows to obtain pale yellow crystals (9.5 g, 61%), melting point 84-85 ^about C.

 CONNECTION PRI me R 63. Methyl ether 5-chloro-2 - [[N- (2'-cyanobiphenyl-4-yl) methyl-N-valeryl] amino] - 3-nitrobenzoic acid.

A mixture of 5-chloro-3-nitro-2-valerylaminobenzoic acid methyl ester (3.15 g), 4- (2-cyanophenyl) benzyl bromide (2.8 g) and potassium carbonate (1.8 g) in dimethylformamide (50 ml) was stirred for 3 hours at room temperature. The reaction mixture was concentrated to dryness, and the concentrate was extracted with ethyl acetate and H ₂ O. The organic layer was washed with water and dried. The solvent is distilled off to form crystals. Recrystallization from a mixture of ethyl acetate and benzene allows to obtain colorless crystals (4.0 g, 79%), 137-138 ^about C.

 CONTROL PRI me R 64. 5-Chloro-3-nitro-2- [[2 '- (N-triphenylmethyl-1H-tetrazol-5-yl) biphenyl methyl ester -4-yl] methyl-N-valeryl] aminobenzoic acid.

 To a solution of 5-chloro-3-nitro-2-valerylaminobenzoic acid methyl ester (0.93 g) in dimethylformamide (10 ml) was added potassium carbonate (0.5 g) and N-triphenylmethyl-5- [2 '- (4 β-bromomethyl) biphenylmethyl] tetrazole (1.84 g). This mixture was stirred for 19 hours at room temperature. Water (50 ml) was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed with water and dried, after which the solvent was distilled off. The residue (3.8 g) was purified by silica gel column chromatography to give pale yellow crystals (1.89 g, 82%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.86 (3H, t); 1.17-1.35 (2H, m.); 1.56-1.80 (2H, m.); 2.03-2.10 (2H, m.); 3.63 (3H, s.); 4.41 (1H, d.); 4.82 (1H, d.); 6.76-6.98 (10H. M.); 7.20-7.54 (12H, m.); 7.88 (1H, d.); 7.90-7.93 (1H, m.); 7.98 (1H, d.).

Infrared spectrum (KBr), cm ^-1 : 1750, 1690, 1555, 1295, 1270, 1225, 760, 710.

 CONFERENCE EXAMPLE 65. 2-Butyl-5-chloro-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-7-carboxylic acid methyl ester .

To a solution of 5-chloro-2- [N- (2'-cyanobiphenyl-4-yl) methyl-N-valeryl] amino-3-nitrobenzoic acid methyl ester (3.33 g) in a mixture of concentrated HCl (4 ml ) and methanol (50 ml) under stirring at room temperature, iron powder (95% purity, 1.1 g) is added in portions. This mixture was stirred for 24 hours at 80 ^C. Thereafter, insoluble materials were filtered off and the filtrate concentrated to dryness. The concentrate was extracted with a mixture of ethyl acetate and water. The organic layer was washed with aqueous sodium bicarbonate and water, and then dried and concentrated. The solvent was distilled off, and the residue was purified by silica gel column chromatography to give colorless needles (1.83 g, 61%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.96 (3H, t); 1.38-1.57 (2H, m.); 1.80-1.95 (2H, m.); 2.92 (2H, t.); 3.72 (3H, s.); 5.79 (2H, s.); 6.94 (2H, d.); 7.41-7.49 (4H, m.); 7.59-7.63 (1H, m.); 7.73-7.78 (1H, m.); 7.61 (1H, d.); 7.91 (1H, d.).

 CONTROL PRI me R 66. Ethyl ester of 2-carboxy-3-nitrobenzoic acid.

 A solution of 3-nitrophthalic acid (35 g) in ethanol (300 ml) containing concentrated sulfuric acid (20 ml) was heated under reflux for 24 hours. The solvent was distilled off and the residue was poured into a mixture of ice-water (700 ml) and extracted with ethyl acetate. The organic layer was washed with water and extracted with an aqueous solution of potassium carbonate. The aqueous layer is made acidic with hydrochloric acid and then extracted with methylene chloride. The organic layer was washed with water and dried. The solvent was distilled off to form a solid product (29 g, 74%), which was used in the subsequent reaction without purification.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.43 (3H, t); 4.47 (2H, q); 7.70 (1H, t.); 8.40 (2H, d.); 9.87 (1H, broad singlet).

Infrared spectrum (nujol), cm ^-1 : 1725, 1535, 1350, 1350, 1300, 1270.

 CONTROL PRI me R 67. Ethyl ester of 2-tert-butoxycarbonylamino-3-nitrobenzoic acid.

 A mixture of 2-carboxy-3-nitrobenzoic acid ethyl ester (23.9 g) and thionyl chloride (12 ml) in benzene (150 ml) was heated under reflux for 3 hours. The resulting solution was concentrated to dryness to form acid chloride (26 g, quantitative yield), which is dissolved in methylene chloride (20 ml). This solution was added dropwise to a mixture of sodium azide (9.75 g) in dimethylformamide (20 ml) under vigorous stirring. The reaction mixture was poured into a mixture of ether and hexane (3 ml 1200 ml) and water, after which the whole mixture was shaken. The organic layer was washed with water and dried, and then the solvent was distilled off. The residue was dissolved in tert-butanol (200 ml), the temperature of the solution was gradually raised with stirring, and then heated under reflux for 2 hours. The reaction mixture was concentrated under reduced pressure, resulting in an oil (30 g).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.40 (3H, t); 1.53 (9H, s.); 4.43 (2H, q); 7.23 (1H, t.); 8.03-8.27 (2H, m.); 9.70 (1H, broad singlet); 1585, 1535, 1500, 1440, 1375, 1265, 1155.

 CONTROL PRI me R 68. Ethyl ester of 2 - [(2'-cyanobiphenyl-4-yl) methyl] aminonitrobenzoic acid.

To a solution of ethyl 2-tert-butoxycarbonylamino-3-nitrobenzoic acid (20 g) in tetrahydrofuran (50 ml) was added sodium hydride (60% oil, 2.8 g), stirring under ice cooling. To this mixture was then added 4- (2-cyanobiphenyl) methyl bromide (18 g) and potassium iodide (0.36 g), followed by stirring for 15 hours at room temperature. The reaction mixture was heated under reflux for 4 hours. The solvent was distilled off, and the residue was extracted with water (250 ml) and ether (200 ml). The organic layer was concentrated to give a yellow oil, which was dissolved in a mixture of trifluoroacetic acid (60 ml) and methylene chloride (40 ml). This solution was stirred for 1 h at room temperature. The reaction mixture was concentrated to dryness and ethyl ether (200 ml) was added to the concentrate, whereby crystals formed. These crystals are collected by filtration, washed with ether and dried, which allows to obtain pale yellow crystals (22.1 g, 85%), melting point 119-120 ^about C.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.37 (3H, t); 4.23 (2H, s.); 4.37 (2H, q); 6.37 (1H, t.); 7.33-7.83 (9H, m.); 7.97-8.20 (2H, m.).

Infrared spectrum (nujol), cm ^-1 : 3280, 2220, 1690, 1575, 1530, 1480, 1450, 1255, 1125, 1105, 755.

 CONTENTION EXAMPLE 69. Ethyl 3-amino-2 - [(2'-cyanobiphenyl-4-yl) methyl] aminobenzoic acid.

 To a solution of 2 - [(2'-cyanobiphenyl-4-yl) methyl] amino-3-nitrobenzoic acid ethyl ester (5.5 g) in tetrahydrofuran (50 ml) was added a skeletal nickel hydrogenation catalyst (5 g). Catalytic reduction is carried out at room temperature and atmospheric pressure. The catalyst was filtered off and the filtrate was concentrated to give a yellow oil (5 g, quantification).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ -P ₂ O) δ: 1.30 (3H, t); 4.23 (2H, s.); 4.27 (2H, q); 6.87-7.03 (2H, m.); 7.33-7.87 (9H, m.).

Infrared spectrum (pure), cm ^-1 : 3435, 3350, 2980, 1690, 1615, 1465, 1365, 1280, 1240, 1215, 1190, 1065, 755.

 CONTROL PRI me R 70. 2-Butyl-1- [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-7-carboxylic acid ethyl ester.

A solution of ethyl 3-amino-2 - [(2'-cyanobiphenyl-4-yl) methyl] benzoate (0.31 g) and ethyl butiroimidokisloty (0.18 g) in ethanol (2 ml) was stirred at ⁷⁰ C for 2 hours. The reaction mixture was concentrated to dryness, the concentrate was extracted with ethyl acetate and aqueous sodium bicarbonate. The organic layer was washed with water, dried and concentrated to form crystals. Recrystallization from a mixture of ethyl acetate and hexane allows to obtain pale yellow needles (0.22 g, 60%), melting point 112-114 ^about C.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.93 (3H, t); 1.20 (3H, t.); 1.33-2.07 (4H, m.); 2.90 (2H, t.); 4.20 (2H, q); 5.87 (2H, s.); 7.00 (2H, d.); 7.17-8.03 (9H, m.).

Infrared spectrum (nujol), cm ^-1 : 2220, 1725, 1480, 1450, 1420, 1400, 1285, 1255, 1245, 1190, 1110, 750.

 CONTENTION EXAMPLE 71. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-hydroxymethylbenzimidazole.

To a solution of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazo-7-carboxylic acid methyl ester (10 g) and NaBH ₄ (2.2 g) in tetrahydrofuran (100 ml) over Methanol (19 ml) was added dropwise 80 min. This mixture was refluxed for 27 hours, after which the reaction mixture was concentrated to dryness. Water was added to the concentrate and neutralized with concentrated HCl. The crystals thus isolated are collected by filtration. Recrystallization from methanol allows to obtain colorless needles (8.8 g, 93%), melting point 203-204 ^about C.

Elemental analysis for C ₂₆ H ₂₅ N ₃ O.

 Calculated, C 78.96; H 6.37; N, 10.62.

 Found, C, 79.24; H 6.36; N + 0.69.

Nuclear Magnetic Resonance Spectrum (200 MHz, CDCl ₃ ) δ: 0.94 (3H, t); 1.36-1.55 (2H, m.); 1.79-1.95 (2H, m.); 2.85 (2H, t.); 4.66 (2H, d.); 5.82 (2H, s.); 7.04 (2H, d.); 7.10 (1H, doublet of doublets); 7.18-7.26 (1H, m.); 7.40-7.52 (4H, m.); 7.64 (1H, double triplet).

Infrared spectrum (KBr), cm ^-1 : 3200, 2210, 1510, 1480, 1455, 1425, 1410, 1280, 1015, 765, 750.

 CONNECTOR PRI me R 72. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-chloromethylbenzimidazole.

To a solution of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-hydroxybenzimidazole (5.4 g) and thionyl chloride (8.3 g) in chloroform (80 ml) was added a catalytic amount of dimethylformamide ( one capsule), after which this mixture was heated under reflux for 1 h. The reaction mixture was washed with aqueous sodium bicarbonate and water, and then dried and concentrated to dryness. The concentrate is crystallized from a mixture of ethyl acetate and hexane to form colorless needles (5.3 g, 92%), melting point 144-145 ^about C.

Elemental analysis for C ₂₆ H ₂₄ ClN ₃ .

 Calculated, C 75.44; H 5.84; N, 10.15.

 Found, C, 75.29; H 5.87; N, 10.04.

Nuclear Magnetic Resonance Spectrum (200 MHz, CDCl ₃ ) δ: 0.96 (3H, t); 1.38-1.57 (2H, m.); 1.82-1.97 (2H, m.); 2.88 (2H, t.); 4.60 (2H, s.); 5.78 (2H, s.); 7.07 (2H, d.); 7.14 (1H, doublet of doublets); 7.21 (1H, d.); 7.41-7.54 (4H, m.); 7.60-7.69 (1H, m.); 7.75-7.84 (2H, m.).

Infrared spectrum (KBr), cm ^-1 : 2210, 1515, 1480, 1450, 1425, 1400, 1350, 1280, 760, 745, 690.

 CONTROL PRI me R 73. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-cyanomethylbenzimidazole.

A mixture of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-chloromethylbenzimidazole (0.83 g) and sodium cyanide (0.12 g) in dimethylformamide (10 ml) was stirred for 22 hours at room temperature. Water was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed with water and dried. The solvent is distilled off, and the residue is crystallized from ethyl acetate with the formation of colorless prisms (0.76 g, 94%), melting point 180-181 ^about C.

Elemental analysis for C ₂₇ H ₂₄ N.

 Calculated, C 80.17; H 5.98; N, 13.85.

 Found, C, 80.22; H 6.17; N, 13.69.

 CONTROL EXAMPLE 74. Ethyl [[2-butyl-1- (2'-cyanobiphenyl-4-yl) methyl] benzimidazol-7-yl] acetate.

 A mixture of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-cyanomethylbenzimidazole (0.76 g) in a 3.5 N solution of hydrochloride in ethanol (10 ml) was heated under reflux for 2.5 hours. The reaction mixture was diluted with water and then made basic with an aqueous solution of sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with water and dried. The solvent was distilled off, and the residue was purified by silica gel column chromatography to give a colorless oil (0.9 g, quantification).

Nuclear Magnetic Resonance Spectrum (200 MHz, CDCl ₃ ) δ: 0.94 (3H, t); 1.23 (3H, t.); 1.37-1.55 (2H, m.); 1.80-1.95 (2H, m.); 2.85 (2H, t.); 3.65 (2H, s.); 4.10 (2H, q); 5.73 (2H, s.); 7.01-7.07 (3H, m.); 7.21 (1H, t.); 7.74-7.68 (5H, m.); 7.71-7.78 (2H, m.).

Infrared spectrum (pure), cm ^-1 : 2210; 1730; 1510, 1475, 1435, 1400, 1365, 1350, 1275, 1040, 760, 735.

 CONTROL PRI me R 75. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-methylbenzimidazole.

A mixture of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-chloromethylbenzimidazole (0.62 g), tributyltin hydride (3.0 g) and superbenzoic acid (catalytic amount) in toluene (20 ml) was heated under reflux under nitrogen atmosphere for 5.5 hours. The reaction mixture was concentrated, purified by silica gel column chromatography and recrystallized from a mixture of ethyl acetate and hexane to give colorless crystals (0.5 g, 88%), melting point 115-116 ^about S.

Elemental analysis for C ₂₆ H ₂₅ N ₃ .

 Calculated, C 82.29; H, 6.64; N, 11.07.

 Found, C 82.30; H 6.74; N, 10.94.

Nuclear Magnetic Resonance Spectrum (200 MHz, CDCl ₃ ) δ: 0.93 (3H, t); 1.35-1.53 (2H, m.); 1.77-1.92 (2H, m.); 2.51 (3H, s.); 2.82 (2H, t.); 5.64 (2H, s.); 6.94 (1H, d.); 7.05 (2H, d.); 7.15 (1H, t.); 7.41-7.53 (4H, m.); 7.60-7.68 (2H, m.); 7.76 (1H, d.).

Infrared spectrum (KBr), cm ^-1 : 2210, 1595, 1480, 1460, 1415, 1400, 1345, 1280, 780, 760, 740.

 CONTROL PRI me R 76. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-hydroxybenzimidazole.

To a solution of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-methoxybenzimidazole (1.2 g) in methylene chloride (5 ml) is added boron tribromide (1.7 g) in a nitrogen atmosphere under 72 ^C. The mixture was stirred for 8 hours at room temperature, water was added and then stirred for a further 1 h. The reaction mixture was basified with 6N. NaOH solution and extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. The concentrate is purified by silica gel column chromatography.

The thus obtained crude crystals were recrystallized from a mixture of ethyl acetate and hexane to give colorless prisms (0.69, 63%), melting point 185-186 ° ^C.

Elemental analysis for C ₂₅ H ₂₃ N ₃ O.

 Calculated, C 78.71; H, 6.08; N, 11.02.

 Found, C, 78.70; H, 6.07; N, 11.01.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.81 (3H, t); 1.22-1.42 (2H, m.); 1.66-1.81 (2H, m.); 2.80 (2H, t.); 5.81 (2H, s.); 6.71 (1H, d.); 7.00 (1H, t.); 7.19-7.26 (3H, m.); 7.38-7.50 (4H, m.); 7.61 (1H, m.); 7.74 (4H, d.).

Infrared spectrum (KBr), cm ^-1 : 2210, 1615, 1590, 1500, 1475, 1440, 1410, 1365, 1290, 1195, 1160, 1065, 780, 755, 725.

 CONTROL PRI me R 77. 2-Methoxy-6-nitroaniline.

A mixture of 2-amino-3-nitrophenol (7.7 g) and potassium carbonate (7.6 g) in dimethylformamide (15 ml) was stirred for 30 minutes at room temperature, and then methyl iodide (7.8 g) was added. This mixture was stirred at room temperature for another 5 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The organic layer is washed with water and then dried. The solvent was distilled off to give crude crystals, which was recrystallized from isopropyl ether provides a orange prisms (6.9 g, 82%), melting point 76-77 ° ^C.

 CONTROL PRI me R 78. N- (2-methoxy-6-nitrophenyl) valeroamide.

To a mixture of 2-methoxy-6-nitroaniline (5.9 g) in valeric anhydride (14 g) was added a catalytic amount of concentrated sulfuric acid and stirred for 1.5 hours at 130-140 ° ^C. To the reaction mixture was added water, followed what make it basic with 6 n. NaOH solution. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and dried. The solvent is distilled off. The residue was purified by silica gel column chromatography. The thus obtained crude crystals were recrystallized from a mixture of ethyl acetate and hexane to give colorless crystals (3.2 g, 36%), melting point 113-114 ° ^C.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.95 (3H, t); 1.33-1.51 (2H, m.); 1.64-1.79 (2H, m.); 2.42 (2H, t.); 3.94 (3H, s.); 7.14 (1H, doublet of doublets); 7.26 (1H, t.); 7.51 (1H, doublet of doublets); 7.64 (1H, broad singlet).

Infrared spectrum (KBr), cm ^-1 : 3300, 1670, 1600, 1590, 1545, 1520, 1485, 1460, 1430, 1360, 1275, 1055, 800, 735.

 CONNECTION PRI me R 79. N- (2'-cyanobiphenyl-4-yl) methyl-N- (2-methoxy-6-nitrophenyl) valeroamide.

 To a solution of N- (2-methoxy-6-nitrophenyl) valeroamide (3.2 g) in dimethylformamide (15 ml) was added sodium hydride (60% oil, 0.61 g) under ice-cooling. This mixture was stirred for 20 minutes and 4- (2-cyanophenyl) benzyl bromide (3.5 g) was added, followed by further stirring for another 1 hour at room temperature. Water was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed with water and dried. The solvent was distilled off, and the residue was purified by silica gel column chromatography to give a yellow oil (5.8 g, quantification).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.84 (3H, t); 1.12-1.35 (2H, m.); 1.56-1.70 (2H, m.); 1.91-2.23 (2H, m.); 3.61 (3H, s.); 4.42 (1H, d.); 5.20 (1H, d.); 7.03-7.12 (1H, m.); 7.22 (2H, d.); 7.34-7.49 (6H, m.); 7.63 (1H, m.); 7.74 (1H, d.).

Infrared spectrum (pure), cm ^-1 : 2220, 1670, 1535, 1480, 1390, 1275, 1050, 800, 760, 730.

 CONNECTOR EXAMPLE 80. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-methoxybenzoimidazole.

To a solution of N - [(2'-cyanobiphenyl-4-yl) methyl] -N- (2-methoxy-6-nitrophenyl) valeroamide (5.8 g) in methanol (50 ml) and concentrated HCl (7 ml ) iron powder (2.3 g) is added in portions while stirring at room temperature. The reaction mixture was refluxed for 5 hours, after which the solvent was distilled off. Ethyl acetate and water were added to the residue, and then it was made basic with 6 N. NaOH solution. Insoluble materials are filtered off, and the filtrate is left to form two layers. The organic layer was washed with water and dried, after which the solvent was removed. The residue was recrystallized from a mixture of ethyl acetate and hexane to give colorless prisms (4.1 g, 80%), mp 126-128 ° ^C. Temperature

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.91 (3H, t); 1.32-1.51 (2H, m.); 1.73-1.89 (2H, m.); 2.79 (2H, t.); 3.83 (3H, s.); 5.71 (2H, s.); 6.60 (1H, d.); 7.11-7.19 (3H, m.); 7.38-7.51 (5H, m.); 7.63 (1H, m.); 7.76 (1H, d.).

Infrared spectrum (KBr), cm ^-1 : 2210, 1605, 1585, 1505, 1480, 1460, 1445, 1420, 1400, 1280, 1255, 1090, 770, 720.

 CONNECTION PRI me R 81. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-methoxymethylbenzimidazole.

 A mixture of 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-hydroxymethylbenzimidazole (0.79 g), thionyl chloride (0.36 g) and dimethylformamide (catalytic amount) in chloroform (20 ml) heated under reflux for 1 h. The solvent was distilled off, and the residue was dissolved in methanol (15 ml). Sodium methylate (4.9 M solution in methanol, 2 ml) was added to the solution, and then heated under reflux for 6 hours. The solvent was distilled off. Water was added to the residue and extracted with ethyl acetate. The organic layer was washed with water and dried, after which the solvent was evaporated. The residue was purified by silica gel column chromatography to give an oil (0.48 g, 59%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.92 (3H, t); 1.20-2.05 (4H, m.); 2.84 (2H, t.); 3.30 (3H, s.); 4.34 (2H, s.); 5.74 (2H, s.); 6.90-7.80 (11H, m.).

Infrared spectrum (pure), cm ^-1 : 2220, 1520, 1480, 1460, 1440, 1425, 1280, 1190, 760.

 The following compounds (control examples 82-84) were obtained in accordance with the procedure described in control example 32.

 CONNECTION PRI me R 82. Ethyl ester of 2- [N-acetyl-N- (2'-cyanobiphenyl-4-yl) methyl] amino-3-nitrobenzoic acid.

 Butter.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.30 (3H, t); 1.97 (3H, s.); 4.17 (1H, d.); 7.17-8.17 (11H, m.).

Infrared spectrum (pure), cm ^-1 : 2985, 2230, 1730, 1675, 1600, 1540, 1390, 1365, 1285, 770.

 CONTENTION EXAMPLE 83. 2- [N-Propionyl-N- (2'-cyanobiphenyl-4-yl) methyl] amino-3-nitrobenzoic acid ethyl ester.

 Butter.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.13 (3H, t); 1.27 (3H, t.); 2.17 (2H, q); 4.13 (2H, q); 4.77 (1H, d.); 4.83 (1H, d.); 7.10, 8.17 (11H, m.).

Infrared spectrum (pure), cm ^-1 : 2985, 2220, 1730, 1675, 1600, 1535, 1480, 1445, 1390, 1350, 1290, 1265, 1210, 770.

 CONTROL EXAMPLE 84. 2- [N-Isobutyl-N- (2'-cyanobiphenyl-4-yl) methyl] amino-3-nitrobenzoic acid ethyl ester.

 Butter.

Spectrum 1 ^H- NMR (900 MHz, CDCl ₃ ) δ: 1.07 (3H, d); 1.13 (3H, d.); 1.30 (3H, t.); 2.03-2.47 (1H, m.); 4.20 (2H, q); 4.70 (1H, d.); 5.13 (1H, d.); 7.17-8.27 (1H, m.).

Infrared spectrum (pure), cm ^-1 : 2980, 2220, 1730, 1670, 1590, 1530, 1480, 1390, 1350, 1285, 1260, 1240, 1205, 765.

 The following compounds (control examples 85-87) were obtained in accordance with the procedure described in control example 33.

 CONTROL PRI me R 85. Ethyl ester of 1 - [(2'-cyanobiphenyl-4-yl) methyl] -2-methylbenzimidazole-7-carboxylic acid.

Melting point 167-168 ^about C (yield 81%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.20 (3H, t); 2.63 (3H, s.); 4.20 (2H, q); 5.83 (2H, s.); 7.00 (2H, d.); 7.17-7.97 (9H, m.).

Infrared spectrum (pure), cm ^-1 : 2220, 1705, 1395, 1280, 1265, 1210.

 CONTROL EXAMPLE 86. 1 - [(2'-Cyanobiphenyl-4-yl) methyl] -2-ethylbenzimidazole-7-carboxylic acid ethyl ester.

Melting point 163-164 ^{° C} (yield 76%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.20 (3H, t) 1.47 (3H, t); 2.93 (2H, q); 4.20 (2H, q); 5.83 (2H, s.); 6.97 (2H, d.); 7.17-8.00 (9H, m.).

Infrared spectrum (nujol), cm ^-1 : 2220, 1720, 1480, 1450, 1420, 1400, 1380, 1280, 1250, 1200, 1145, 1110.

 CONTENTION EXAMPLE 87. 1 - [(2'-Cyanobiphenyl-4-yl) methyl] -2-isopropylbenzimidazole-7-carboxylic acid ethyl ester.

Melting point 107-108 ^{° C} (yield 77%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.17 (3H, t); 1.43 (6H, d.); 3.03-3.47 (1H, m.); 4.17 (2H, q); 5.87 (2H, s.); 6.93 (2H, d.); 7.17-7.80 (8H, m.); 7.96 (1H, d.).

Infrared spectrum (nujol), cm ^-1 : 2220, 1730, 1440, 1400, 1280, 1250, 1205, 1140, 1110, 765, 740.

 CONTENTION EXAMPLE 88. Ethyl 2-chloromethyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-7-carboxylic acid.

To an ice-cooled solution of 3-amino-2 - [(2'-cyanobiphenyl-4-yl) methyl] aminobenzoic acid ethyl ester (1.0 g), triethylamine (0.3 g) and methylene chloride (10 ml), chloroacetyl chloride was added in portions (0.24 ml). This mixture was stirred for 13 hours and then evaporated to dryness to form a residue. The residue was washed with H ₂ O, dried and dissolved in ethanol (10 ml). Concentrated HCl (1 ml) was added to this solution and heated under reflux for 6 hours. The reaction solution was evaporated to dryness to form a residue, which was dissolved in methylene chloride and water. The solution is made basic using 1 N. NaOH solution, the organic layer is washed with water, dried and evaporated to dryness to form crystals.

 Recrystallization from a mixture of ethyl acetate and isopropyl ether gave colorless crystals (0.88 g, 76%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 1.21 (3H, t); 4.21 (2H, q); 4.83 (2H, s.); 6.02 (2H, s.); 7.02 (2H, d.); 7.28-7.49 (5H, m.); 7.58-7.79 (3H, m.); 8.00 (1H, doublet of doublets).

 CONTROL EXAMPLE 89. 1 - [(2'-Cyanobiphenyl-4-yl) methyl] -2-methoxymethylbenzimidazole-7-carboxylic acid ethyl ester.

A solution of ethyl 2-chloromethyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-7-carboxylic acid (0.8 g) and NaOMe (1.08 g, 28% solution in methanol) in methanol (15 ml) was heated under reflux for 2 hours. The reaction solution was evaporated to dryness to form a residue, which was dissolved in CH ₂ Cl ₂ -H ₂ O. The organic layer was washed with H ₂ O, dried and evaporated to dry condition with the formation of syrup. This syrup was purified by chromatography on silica gel columns, whereby a yellow syrup (0.4 g, 52%) was obtained.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 3.43 (3H, s.); 3.72 (3H, s.); 4.78 (2H, s.); 5.97 (2H, s.); 6.99 (2H, d.); 7.25-7.49 (5H, m.); 7.55-7.77 (3H, m.); 7.99 (1H, doublet of doublets).

 The following compounds (control examples 90-93) were obtained in accordance with a method similar to that described in control example 89.

 CONNECTION PRI me R 90. Ethyl ester 1 - [(2'-cyanobiphenyl-4-yl) methyl] -2-ethoxymethylbenzimidazole-7-carboxylic acid.

 Pale brown syrup (92%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 1.16 (3H, t); 1.23 (3H, t.); 3.59 (2H, q); 4.21 (2H, q); 4.82 (2H, s.); 5.99 (2H, s.); 6.99 (2H, d.); 7.24-7.45 (5H, m.); 7.55-7.75 (3H, m.); 7.98 (1H, doublet of doublets).

 CONTROL EXAMPLE 91. 1 - [(2'-Cyanobiphenyl-4-yl) methyl] -2-methylthiomethylbenzimidazole-7-carboxylic acid ethyl ester.

 Pale yellow syrup (72%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 1.20 (3H, t); 2.18 (3H, s.); 3.90 (2H, s.); 4.20 (2H, q); 5.96 (2H, s.); 7.01 (2H, d.); 7.23-7.35 (1H, m.); 7.37-7.50 (4H, m.); 7.59-7.80 (3H, m.); 7.97 (1H, doublet of doublets).

 CONTROL PRI me R 92. Ethyl ether 1 - [(2'-cyanobiphenyl-4-yl) methyl] -2-ethylthiomethylbenzimidazole-7-carboxylic acid.

 Pale brown syrup (88%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 1.20 (3H, t); 1.27 (3H, t.); 2.62 (2H, q); 3.96 (2H, s.); 4.20 (2H, q); 6.00 (2H, s.); 7.01 (2H, d.); 7.29 (1H, t.); 7.38-7.49 (4H, m.); 7.57-7.78 (3H, m.); 7.96 (1H, doublet of doublets).

 CONNECTION PRI me R 93. Ethyl ester 2-acetoxymethyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-7-carboxylic acid.

 Pale brown syrup (99%).

 CONNECTION PRI me R 94. 3-amino-2 - [(2'-cyanobiphenyl-4-yl) methyl] aminobenzoic acid methyl ester.

A mixture of 3-amino-2 - [(2'-cyanobiphenyl-4-yl) methyl] aminobenzoic acid ethyl ester (5 g) and NaH (60% oil, 1.62 g) in methanol (50 ml) was stirred at room temperature within 24 hours. The reaction mixture was concentrated to dryness to form a syrup, which was poured into a saturated aqueous solution of NaHCO ₃ (100 ml). This mixture was extracted with chloroform, and the organic layer was washed with H ₂ O, dried and evaporated to dryness, resulting in a crystalline product.

Recrystallization from a mixture of ethyl acetate and hexane led to the formation of colorless crystals (3.9 g, 82%), melting point 106-108 ^about C.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 3.81 (3H, s.); 3.97 (2H, broad singlet); 4.23 (2H, s.); 6.40 (1H, broad singlet); 6.88-6.91 (2H, m.); 7.34-7.55 (7H, m.); 7.64 (1H, double triplet); 7.77 (1H, doublet of doublets).

Infrared spectrum (KBr), cm ^-1 : 3410, 3350, 2225, 1695, 1485, 1470, 1290, 1200, 780, 760.

 CONNECTION PRI me R 95. 2- (2-Chloroethyl) -1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-7-carboxylic acid methyl ester .

To a cold solution of 3-amino-2 - [(2'-cyanobiphenyl-4-yl) methyl] amino-benzoic acid methyl ester (0.5 g) in CH ₂ Cl ₂ (5 ml) was added dropwise 3-chloropropionyl chloride ( 0.15 ml). The reaction mixture was stirred at room temperature for 30 minutes and then concentrated to dryness to form a residue. This residue was dissolved in methanol (5 ml) containing concentrated HCl (0.5 ml), after which this solution was stirred at room temperature for 16 hours. The reaction solution was concentrated to dryness to form a residue, which was dissolved in CH ₂ Cl ₂ -H ₂ O. The aqueous layer is made basic and then extracted. The organic layer was washed with H ₂ O, dried and evaporated to dryness to form a pale brown syrup (0.7 g, 100%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 3.37 (2H, t); 3.74 (3H, s.); 4.09 (2H, t.); 5.87 (2H, s.); 7.00 (2H, d.); 7.29 (1H, t.); 7.39-7.81 (7H, m.); 7.97 (1H, doublet of doublets).

 CONNECTION PRI me R 96. 1 - [(2'-Cyanobiphenyl-4-yl) methyl] -2- (2-methoxyethyl) benzimidazole-7-carboxylic acid methyl ester .

A mixture of 2- (2-chloroethyl) -1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-7-carboxylic acid methyl ester (1.0 g) and K ₂ CO ₃ (0.25 g) in methanol (30 ml) was refluxed for 2 hours. The reaction mixture was concentrated to dryness to form a residue. This residue was dissolved in CH ₂ Cl ₂ , and the insoluble material was filtered off. The filtrate was concentrated to dryness, and the resulting syrup was purified by chromatography on silica gel columns, resulting in a pale yellow syrup (0.45 g, 59%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 3.19 (2H, t); 3.34 (3H, s.); 3.72 (3H, s.); 3.92 (2H, t.); 5.88 (2H, s.); 7.00 (2H, d.); 7.26 (1H, t.); 7.40-7.48 (4H, m.); 7.56-7.76 (3H, m.); 7.95 (1H, doublet of doublets).

 CONTROL PRI me R 97. 1 - [(2'-Cyanobiphenyl-4-yl) methyl] -2- (2-methylthiomethyl) benzimidoazole-7-carboxylic acid methyl ester .

 This compound was obtained in accordance with a method similar to that described in control example 96.

 Colorless powder (1.1 g, 93%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 2.14 (3H, s.); 3.02-3.11 (2H, m.); 3.16-3.25 (2H, m.); 3.74 (3H, s.); 5.86 (2H, s.); 7.00 (2H, d.); 7.28 (1H, t.); 7.39-7.49 (4H, m.); 7.58-7.78 (3H, m.); 7.97 (1H, doublet of doublets).

 CONTECTOR EXAMPLE 98. 2-Butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7- (N, N-dimethylaminoethyl) benzimidazole.

 A mixture of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-chloromethylbenzimidazole (0.65 g) and dimethylamine (50% aqueous solution, 1.5 ml) in ethanol (3 ml) heated in a sealed tube for 5 hours. The reaction solution was concentrated to dryness and the resulting syrup was dissolved in ethyl acetate. This solution was washed with water, dried and evaporated to dryness to form a syrup, which was purified by chromatography on silica gel columns, which afforded a colorless syrup (0.4 g, 63%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.92 (3H, t); 1.35-1.53 (2H, m.); 1.71-1.94 (2H, m.); 2.16 (6H, s.); 2.80 (2H, t.); 3.34 (2H, s.); 6.00 (2H, s.); 6.95-7.01 (3H, m.); 7.16 (1H, t.); 7.39-7.50 (4H, m.); 7.62 (1H, m.); 7.73-7.77 (2H, m.).

Infrared spectrum (pure), cm ^-1 : 2210, 1515, 1480, 1460, 1440, 1405, 1360, 1330, 1275, 1005, 840, 785, 760.

 CONNECTION PRI me R 99. Ethyl ester of 1 - [(2'-cyanobiphenyl-4-yl) methyl-2-sec-butylbenzimidazole-7-carboxylic acid.

A mixture of 3-amino-2 - [(2'-cyanobiphenyl-4-yl) methyl] aminobenzoic acid ethyl ester (1.1 g) and 2-methylbutyric acid anhydride (0.56 g) in pyridine (2 ml) is heated at 115 ^{° C} for 15 hours. The reaction mixture was boiled with ethyl acetate (50 ml) and the solution was washed with water, dried and evaporated to dryness to give a syrup. This syrup was dissolved in ethanol (15 ml) containing concentrated HCl (0.5 ml), and the solution was heated under reflux for 3 hours. After removal of the solvent, the obtained syrup was purified by silica gel column chromatography, which resulted in a pale yellow syrup (1.2 g, 92%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.90 (3H, t); 1.20 (3H, t.); 1.40 (3H, d.); 1.50-2.10 (1H, m.); 4.17 (2H, q); 5.86 (2H, s.); 6.97 (2H, d.); 7.17-8.03 (9H, m.).

Infrared spectrum (pure), cm ^-1 : 2975, 2930, 2875, 2220, 1480, 1445, 1410, 1370, 1280, 1200, 1140, 1110, 1035, 760.

 CONTROL PRI me R 100. Ethyl ester 1 - [(2'-cyanobiphenyl-4-yl) methyl] -2-isobutylbenzimidazole-7-carboxylic acid.

 This compound was obtained in accordance with a method similar to that described in control example 99.

 Pale yellow (quantitative yield).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.03 (6H, d); 1.20 (3H, t.); 2.07-2.53 (1H, m.); 2.80 (2H, d.); 4.17 (2H, q); 5.83 (2H, s.); 6.93 (2H, d.); 7.13-8.00 (9H, m.).

Infrared spectrum (pure), cm ^-1 : 2960, 2215, 1710, 1480, 1400, 1280, 1255, 1200, 1120, 760.

 CONNECTION PRI me R 101. 2-Butyl-1 - [[2 '- (N-triphenylmethyltetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole -7 - carboxylic acid.

Mixture of 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (3.0 g), triphenylmethyl chloride (1.96 g) and triethylamine (1.0 ml) in CH ₂ Cl ₂ (20 ml) was stirred at room temperature for 16 hours. The reaction solution was washed with H ₂ O, dried over Na ₂ SO ₄ and concentrated to dryness to form a solid residue. This residue was purified by chromatography on a silica gel column, whereby was obtained a colorless powder (4.25 g, 91%), melting point 120-123 ° ^C.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.88 (3H, t); 1.26-1.45 (2H, m.); 1.72-1.88 (2H, m.); 2.81 (2H, t.); 5.72 (2H, s.); 6.63 (2H, d.); 6.92-6.97 (8H, m.); 7.12-7.43 (13H, m.); 7.68 (1H, d.); 7.78-7.83 (1H, m.); 7.92 (1H, d.).

Infrared spectrum (pure), cm ^-1 : 3050, 2950, 2925, 1690, 1595, 1510, 1490, 1440, 1405, 1275, 1240, 1180, 740, 690.

 EXAMPLE 1. 2-Butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

A mixture of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-7-carboxylic acid methyl ester (3.2 g), sodium azide (7.4 g) and ammonium chloride (6.1 g) in dimethylformamide (30 ml) was stirred at 115 ^about C for 4 days. Water was added to the reaction mixture with 1 N. HCl solution adjusted pH to 3-4. The resulting crude crystals (1) are purified by silica gel column chromatography. The crystals thus obtained were recrystallized from a mixture of ethyl acetate and methanol to give colorless prisms (2.27 g, 63%), melting point 168-169 ° ^C.

Elemental analysis for C ₂₆ H ₂₄ N ₆ O ₂ · H ₂ O.

 Calculated, C 66.37; H 5.57; N, 17.86.

 Found, C, 66.04; H, 5.69; N, 17.58.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.88 (3H, t.); 1.28-1.46 (2H, m.); 1.65-1.80 (2H, m.); 2.82 (2H, t.); 5.85 (2H, s.); 6.79 (2H, d.); 7.00 (2H, d.); 7.24 (1H, t.); 7.45 (5H, m.); 7.83 (1H, doublet of doublets).

Infrared spectrum (KBr), cm ^-1 : 1720, 1600, 1510, 1455, 1285, 1255, 1240, 775, 755, 745.

 EXAMPLE 2. 2-Butyl-1 - [[2 '- (N-methyltetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

The crude crystals (1) obtained in working example 1 are purified by silica gel column chromatography followed by recrystallization from a mixture of ethyl acetate and hexane, whereby colorless needles (0.17 g, 4.7%) are obtained, melting point 133- 135 ^about S.

Elemental analysis for C ₂₇ H ₂₆ N ₆ O ₂ .

 Calculated, C 69.51; H 5.62; N, 18.01.

 Found, C, 69.47; H 5.66; N, 17.92.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.94 (3H, t); 1.35-1.55 (2H, m.); 1.78-1.93 (2H, m.); 2.96 (2H, t.); 3.15 (3H, s.); 5.82 (2H, s.); 6.81 (2H, d.); 6.97 (2H, d.); 7.25 (1H, t.); 7.48-7.67 (4H, m.); 7.80 (1H, doublet of doublets); 7.95 (1H, doublet of doublets).

Infrared spectrum (KBr), cm ^-1 : 1715, 1520, 1415, 1290, 1260, 1200, 1125, 780, 750.

 EXAMPLE 3. 2-Butyl-N-isopropyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7 carboxamide.

Solution of 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (0.71 g) and diethyl cyanophosphate (purity 90% 0.82 d) in dimethylformamide (6 ml) was stirred under ice cooling for 1 h. To this solution isopropylamine hydrochloride (0.14 g) and triethylamine (0.61 g) were then added, after which this mixture was stirred at room temperature for 2 o'clock To the reaction mixture add water and neutralize 1 N. HCl solution, followed by extraction with ethyl acetate. The organic layer was washed with water, dried and concentrated to dryness. Recrystallization of the thus obtained crude crystals from a mixture of methanol and ethyl acetate afforded colorless prisms (0.31 g 41%), melting point 247-249 ° ^C.

Elemental analysis for C ₂₉ H ₃₂ N ₇ O · 1/5 H ₂ O
Calculated, C 69.91; H 6.55; N, 19.68.

 Found, C 69.91; H, 6.30; N, 19.87.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.87 (3H, t.); 0.93 (6H, d.); 1.26-1.44 (2H, m.); 1.62-1.77 (2H, m.); 2.80 (2H, t.); 3.85-3.95 (1H, m.); 5.67 (2H, s.); 6.84 (2H, d.); 6.99 (2H, d.); 7.16-7.24 (2H, m.); 7.44 (1H, d.); 7.51-7.72 (4H, m.); 8.27 (1H, d.).

Infrared spectrum (KBr), cm ^-1 : 1640, 1540, 1510, 1455, 1415, 755, 740.

 EXAMPLE 4. 2-Sodium salt of 2-butyl-1 - [[2'- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7 -carboxylic acid.

2-Butyl-1- [2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methylbenzimidazole-7-carboxylic acid (0.2 g) was added to methanol (15 ml) containing NaOCH ₃ (46 mg), after which this mixture was stirred at room temperature for 15 minutes. Toluene (30 ml) was added to the reaction mixture and concentrated under reduced pressure to give crystals. The separated crystals were collected by filtration, whereby colorless powdery crystals were obtained (0.14 g, 62%), melting point 255-257 ^C (decomposition).

Elemental analysis for C ₂₆ H ₂₂ N ₆ Na ₂ O ₂ · 2H ₂ O
Calculated, C 58.64; H 4.92; N, 15.78.

 Found, C, 58.98; H 4.60; N, 15.66.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.85 (3H, t.); 1.27-1.39 (2H, m.); 1.59-1.74 (2H, m.); 2.69 (2H, t.); 6.10 (2H, s.); 6.81 (2H, d.); 6.98-7.07 (3H, m.); 7.19-7.53 (6H, m.).

Infrared spectrum (KBr), cm ^-1 : 1610, 1410, 1360, 760.

 EXAMPLE 5 2-Butyl-1 butyl ether - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carbon acids.

A mixture of 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (0.47 g) and concentrated sulfuric acid (0.1 ml ) in butanol (10 ml) was heated under reflux for 66 hours. The solvent was removed by evaporation. Water was added to the residue and the pH of the mixture was adjusted to 3-4 with 1 N. NaOH solution, after which this mixture was extracted with ethyl acetate. The organic layer was washed with water and dried. After removal of solvent, the residue was purified by silica gel column chromatography. Recrystallization from a mixture of ethyl acetate and hexane allowed to obtain colorless prisms (0.15 g, 29%), melting point 192-193 ^about C.

Elemental analysis for C ₃₀ H ₃₂ N ₆ O ₂ .

Calculated, C 70.84; H 6.34; N, 16.52;
Found, C, 70.99; H, 6.46; N, 16.25.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.83 (3H, t); 0.85 (3H, t.); 1.18-1.39 (4H, m.); 1.45-1.64 (4H, m.); 2.38 (2H, t.); 3.99 (2H, t.); 5.50 (2H, s.); 6.47 (2H, d.); 6.79 (2H, d.); 6.93 (1H, d.); 7.04 (1H, t.); 7.27-7.32 (1H, m.); 7.50 (1H, doublet of doublets); 7.56-7.68 (2H, m.); 7.97-8.01 (1H, m.).

Infrared spectrum (KBr), cm ^-1 : 1710, 1465, 1455, 1415, 1280, 1265, 1125, 760.

 EXAMPLE 6. (4-Pyridyl) methyl ester 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) -biphenyl-4-yl] methyl ] benzimidazole-7-carboxylic acid.

A solution of (4-pyridyl) methyl ester of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-7-carboxylic acid (0.61 g) and trimethyltin azide (0.75 g) in toluene (10 ml) is heated under reflux in a nitrogen atmosphere for 4 days. After removing the solvent, the resulting residue was dissolved in ethanol (5 ml). To this solution is added 1 N. HCl solution (8 ml), after which this mixture was stirred for 5 min at room temperature, and then neutralized with 1 N. NaOH solution and extracted with ethyl acetate. The extract is washed with water, dried and evaporated to dryness. The resulting residue was purified by silica gel column chromatography to give crystals. Recrystallization from a mixture of ethyl acetate and hexane allowed to obtain colorless prisms (0.54 g, 83%), melting point 179-180 ^about C.

Elemental analysis for C ₃₂ H ₂₉ N ₇ O ₂ .

 Calculated, C 70.70; H 5.38; N, 18.04.

 Found, C, 70.96; H 5.45; N, 18.02.

Spectrum 1 ^H- NMR (200, CDCl ₃ ) δ: 0.80 (3H, t); 1.18-1.36 (2H, m.); 1.53-1.68 (2H, m.); 2.49 (2H, t.); 5.19 (2H, s.); 5.51 (2H, s.); 6.44 (2H, d.); 6.79 (2H, d.); 7.15-7.31 (4H, m.); 7.47-7.61 (3H, m.); 7.67 (1H, doublet of doublets); 7.92 (1H, doublet of doublets); 8.35 (2H, d.).

Infrared spectrum (KBr), cm ^-1 : 1720, 1600, 1410, 1280, 1250, 1120, 760, 750, 740.

 EXAMPLE 7. 2-Propyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Mixture of 2-propyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-7-carboxylic acid methyl ester (2.5 g), sodium azide (3.9 g) and ammonium chloride (3.2 g) in dimethylformamide (30 ml) is stirred at 110-120 ^about C for 5 days. Water was added to the reaction mixture, this solution was acidified (pH 3-4) and then extracted with ethyl acetate. The organic layer was washed with water and dried. After removal of solvent, the residue was purified by silica gel column chromatography to give crystals. Recrystallization from a mixture of dimethylformamide and ethanol afforded colorless crystals (0.8 g, 23%), melting point 275-276 ^C (decomposition).

Elemental analysis for C ₂₅ H ₂₂ N ₆ O ₂ · 1 / 2H ₂ O
Calculated, C 67.10; H 5.18; N, 18.78.

 Found, C, 67.19; H 4.95; N, 18.84.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ CF ₃ COOH) δ: 1.10 (3H, t); 1.70-2.20 (2H, m.); 5.23 (2H, t,); 5.97 (2H, s.); 6.90 (2H, d.); 7.13 (2H, d.); 7.47-7.80 (5H, m.); 8.03-8.17 (2H, m.).

Infrared spectrum (KBr), cm ^-1 : 3070, 2720, 2440, 1700, 1450, 1410, 1405, 1285, 1235, 1200, 1190, 1120, 755.

 EXAMPLE 8. 2-Pentyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Mixture of 1 - [(2'-cyanobiphenyl-4-yl) methyl] -2-pentylbenzimidazole-7-carboxylic acid methyl ester (3.25 g), sodium azide (2.6 g) and ammonium chloride (2.1 g ) in dimethylformamide (20 ml) was stirred at 110-120 ^about C for 5 days. Water is added to the reaction mixture, it is made acidic (pH 3-4) with 1N. HCl solution and then extracted with ethyl acetate. The organic layer was washed with water and dried. After removal of solvent, the residue was purified by silica gel column chromatography to give crystals. Recrystallization from a mixture of ethyl acetate and ethanol, followed by treatment with hot water yielded colorless powdery crystals (1.0 g, 29%), melting point 205-207 ^C (decomposition).

Elemental analysis for C ₂₇ H ₂₆ N ₆ O ₂ · 1 / 5H ₂ O
Calculated, C 68.98; H 5.66; N, 17.88.

 Found, C, 69.14; H 5.60; N, 17.90.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ -CF ₃ COOH) δ: 0.87 (3H, t); 1.13-1.53 (4H, m.); 1.67-2.10 (2H, m.); 3.27 (2H, t.); 6.00 (2H, s.); 6.93 (2H, d.); 7.17 (2H, d.); 7.47-7.90 (5H, m.); 8.07-8.20 (2H, m.).

Infrared spectrum (nujol), cm ^-1 : 3040, 2775, 1695, 1485, 1450, 1425, 1410, 1290, 1240, 1200, 755.

 EXAMPLE 9 Methyl 2-butyl-5-methyl-1 - [[2 '- (1H-tetrazol-5-yl) -biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Mixture of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -5-methylbenzimidazole-7-carboxylic acid methyl ester (2.8 g), sodium azide (6.2 g) and ammonium chloride (5.1 g) in dimethylformamide (25 ml) was stirred at 110-120 ^C for 3 days. The reaction mixture was diluted with water, acidic (pH 3-4) with 1N. HCl solution and then extracted with ethyl acetate. The organic layer was washed with water and dried. After removal of solvent, the residue was purified by silica gel column chromatography to give crystals. Recrystallization from a mixture of ethyl acetate and methanol allowed to obtain colorless prisms (0.72 g, 24%), melting point 144-145 ^about C.

Elemental analysis for C ₂₈ H ₂₈ N ₆ O ₂ · 0.1 H ₂ O
Calculated, C 69.72; H 5.89; N, 17.42.

 Found, C, 69.58; H 5.89; N, 17.28.

Spectrum 1 ^H- NMR (20 MHz, CDCl ₃ ) δ: 0.82 (3H, t); 1.17-1.37 (2H, m.); 1.45-1.60 (2H, m.); 2.26 (3H, m.); 2.34 (2H, t.); 3.56 (3H, s.); 5.23 (2H, s.); 6.43 (2H, d.); 6.60 (1H, s.); 6.76 (2H, d.); 7.28-7.32 (2H, m.); 7.59-7.69 (2H, m.); 7.9-8.0 (1H, m.).

Infrared spectrum (KBr), cm ^-1 : 1715, 1515, 1455, 1440, 1410, 1315, 1255, 1225, 1050, 785, 765.

 EXAMPLE 10. 2-Butyl-5-methyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7 -carboxylic acid.

Mixture of methyl 2-butyl-5-methyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (0.15 g) in 1 n . a solution of NaOH (1.2 ml) and methanol (2 ml) was heated under reflux for 2 hours. The reaction mixture was diluted with water, washed with ether and made acid (pH 3-4) with 1 N. HCl solution. The separated crystals were collected by filtration and recrystallized from ethyl acetate to give colorless crystals (0.1 g, 71%), melting point 175-178 ^C (decomposition).

Elemental analysis for C ₂₇ H ₂₆ N ₆ O ₂ · 1 / 2H ₂ O.

 Calculated, C 68.19; H 5.72; N, 17.67.

 Found, C, 68.25; H 5.66; N, 17.59.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.87 (3H, t.); 1.25-1.44 (2H, m.); 1.63-1.77 (2H, m.); 2.41 (3H, s.); 2.79 (2H, t.); 5.82 (2H, s.); 6.76 (2H, d.); 6.99 (2H, d.); 7.45-7.49 (2H, m.); 7.55-7.69 (4H, m.).

Infrared spectrum (KBr), cm ^-1 : 3440, 1700, 1600, 1515, 1450, 1410, 1310, 1240, 765.

 EXAMPLE 11 2-Butyl-6-methyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole ethyl ester -7-carboxylic acid.

A mixture of 6-methyl-3-nitro [N- (2 '- (N-triphenylmethyltetrazol-5-yl) biphenyl-4-yl) methyl-N-va lerolic acid ethyl ester (2.1 g) and iron powder ( 0.73 g) in concentrated HCl (2.1 ml) and ethanol (10 ml) are heated under reflux for 18 hours. Insoluble materials in the reaction mixture are filtered. Then the filtrate is concentrated to dryness. The residue was dissolved in 1N NaOH and the precipitates formed were filtered through celite. The filtrate was acidified with concentrated HCl. The oil product was separated and extracted with methylene chloride. The extract is washed with water and concentrated to dryness. The syrup-like product thus obtained is purified by chromatography on silica gel columns to form a crystalline product. Recrystallization from ethyl acetate and isopropyl ether afforded pale brown prisms (0.8 g, 59%), melting point 164-165 ° ^C.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.84, 1.06 (each 3H, t.); 1.20-1.39 (2H, m.); 1.48-1.63 (2H, m.); 2.32 (3H, s.); 2.38 (2H, t.); 3.88 (2H, q); 5.28 (2H, s.); 6.56 (2H, d.); 6.74 (1H, d.); 6.86 (3H, doublet of doublets); 7.28-7.33 (1H, m.); 7.58-7.63 (2H, m.); 7.91-7.97 (1H, m.).

 EXAMPLE 12 Methyl 2-butyl-5-chloro-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole -7-carboxylic acid.

With a mixture of 5-chloro-3-nitro-2- [N- [2 '- (N-triphenylmethyl-1H-tetrazol-5-yl) biphenyl-4-yl] methyl] -N-valerylanthranic acid methyl ester (1 , 26 g), concentrated HCl (1.6 ml) and iron powder (95% purity, 0.45 g) in methanol (15 ml) are heated under reflux for 20 hours. Insoluble materials are filtered off and the filtrate is concentrated. The concentrate was extracted with ethyl acetate and water. An aqueous solution of sodium bicarbonate is added to the organic layer, and insoluble materials formed in this way are filtered off. The filtrate was washed with water, dried and concentrated. The concentrate was purified by column chromatography on silica gel to give crystals, which was recrystallized from a mixture of ethyl acetate and benzene afforded colorless crystals (0.59 g, 74%), melting point 132-133 ° ^C.

Elemental analysis for C ₂₇ H ₂₅ N ₆ O ₂ Cl.

 Calculated, C 64.73; H 5.03; N, 16.77.

 Found, C, 64.49; H 5.06; N, 16.50.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.84 (3H, t); 1.23-1.41 (2H, m.); 1.52-1.68 (2H, m.); 2.50 (2H, t.); 3.62 (3H, s.); 5.48 (2H, s.); 6.46 (2H, d.); 6.83 (2H, d.); 6.93 (1H, m.); 7.31-7.36 (1H, m.); 7.49 (1H, d.); 7.63-7.68 (2H, m.); 7.98-8.00 (1H, m.).

Infrared spectrum (KBr), cm ^-1 : 2960, 2875, 1720, 1510, 1460, 1430, 1400, 1280, 1230, 1190, 750.

 EXAMPLE 13. 2-Butyl-5-chloro-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7 -carboxylic acid.

A solution of methyl 2-butyl-5-chloro-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (0.28 g) in 1 n . NaOH solution (2 ml) and methanol (4 ml) were stirred at room temperature for 16 hours. The reaction mixture was concentrated, the concentrate was dissolved in water (10 ml) and this solution was acidified with 1N. HCl solution. The isolated crystals thus collected by filtration and recrystallized from a mixture of methanol and chloroform to give colorless crystals (0.2 g, 72%), melting point 232-234 ° ^C.

Elemental analysis for C ₂₆ H ₂₃ N ₆ O ₂ Cl · 1 / 2H ₂ O
Calculated, C 62.99; H 4.88; N, 16.94.

 Found, C, 63.01; H 4.81; N, 16.87.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.87 (3H, t.); 1.26-1.45 (2H, m.); 1.64-1.79 (2H, m.); 2.82 (2H, t.); 5.81 (2H, s.); 6.78 (2H, d.); 7.00 (2H, d.); 7.45-7.69 (5H, m.); 7.91 (1H, d.).

Infrared spectrum (KBr), cm ^-1 : 2975, 2930, 2875, 1705, 1480, 1460, 1400, 1270, 1240, 1220, 1190, 870, 780, 740.

 EXAMPLE 14 2-Butyl-1 Ethyl Ester - [[2'- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carbon acids.

A mixture of ethyl 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-7-carboxylic acid (0.21 g), sodium azide (1.3 g) and ammonium chloride (1.07 g) in dimethylformamide (8 ml) is stirred at 110-120 ^about C for 60 hours. Water is added to this mixture and it is acidic (pH 3-4) with 1N. HCl solution, and then extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated to dryness. To the concentrate was added ether, the resulting crude crystals were collected by filtration and recrystallized from ethanol to yield colorless crystals (0.95 mg, 41%), melting point 138-139 ° ^C.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.80 (3H, t); 1.07-1.77 (7H, m.); 2.37 (2H, t.); 4.07 (2H, q); 5.50 (2H, s.); 6.47 (2H, d.); 6.80 (2H, d,), 7.00-7.10 (2H, m.); 7.23-7.73 (4H, m.); 7.90-8.10 (1H, m.).

Infrared spectrum (nujol), cm ^-1 : 1715, 1410, 1290, 1260, 1125, 1040, 750.

 EXAMPLE 15. 2-Butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

A mixture of ethyl 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-6-carboxylic acid (80 mg) in 2-methoxyethanol (1.5 ml ) and 2 N. NaOH solution (1.5 ml) was stirred at 110-120 ^about C for 1 h. The reaction mixture was neutralized with 2 N. HCl solution, and then concentrated to dryness. The concentrate is dissolved in chloroform. After removal of insoluble materials by filtration, the filtrate was concentrated to dryness. The crude crystals thus obtained were recrystallized from aqueous ethanol to give colorless crystals (60 mg, 77%).

The melting temperature, the data of the spectrum of 1 ^H- NMR and infrared spectrum correspond to similar indicators obtained in working example 1.

 EXAMPLE 16. 2-Butyl-7-hydroxymethyl-1 - [[2'- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole.

A mixture of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-hydroxymethylbenzimidazole (0.4 g), sodium azide (0.98 g) and ammonium chloride (0.8 g) in dimethylformamide (4 ml) was stirred at 110-120 ^about C for 4 days. Water was added to the reaction mixture and extracted with ethyl acetate. The extract is washed with water and dried. After removing the solvent, the residue is crystallized from a mixture of ethyl acetate and methanol with the formation of colorless needles, melting point 152-153 ^about C.

Elemental analysis for C ₂₆ H ₂₆ N ₆ O · 1 / 2C ₄ H ₈ O ₂ · 1 / 10H ₂ O
Calculated, C 69.43; H 6.28; N, 17.35.

 Found, C, 69.14; H, 6.22; N, 17.59.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.86 (3H, t); 1.26-1.44 (2H, m.); 1.63-1.78 (2H, m.); 2.76 (2H, t.); 4.47 (2H, s.); 5.47 (1H, broad singlet); 5.76 (2H, s.); 6.81 (2H, d.); 7.04 (2H, d.); 7.08-7.16 (2H, m.); 7.49-7.70 (5H, mu).

Infrared spectrum (KBr), cm ^-1 : 1510, 1450, 1405, 1020, 755, 740.

 EXAMPLE 17 Ethyl ether [[2-butyl-1- (2'- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7- sludge) acetic acid.

A mixture of ethyl 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] benzimidazole-7-carboxylic acid (0.86 g), sodium azide (0.5 g) and ammonium chloride (1.6 g) in dimethylformamide (10 ml) is stirred in dimethylformamide at 110-120 ^about C for 4.5 days. Water was added to the reaction mixture and acidified (pH 3-4) with 1N. HCl solution and then extracted with ethyl acetate. The organic layer was washed with water and dried, after which it was distilled off with a solvent. The residue was purified by silica gel column chromatography to give crude crystals. Recrystallization from ethyl acetate allowed to obtain colorless needles (0.53 g, 56%), melting point 129-130 ^about C.

Elemental analysis for C ₂₉ H ₃₀ N ₆ O ₂ · 0.4H ₂ O
Calculated, C 69.41; H, 6.19; N, 16.75.

 Found, C, 69.50; H 5.94; N, 17.03.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.83 (3H, t); 1.12-1.33 (5H, m.); 1.48-1.63 (2H, m.); 2.24 (2H, t.); 3.41 (2H, s.); 4.03 (2H, q); 5.46 (2H, s.); 6.55-6.66 (3H, m. (; 6.87 (2H, d)); 6.93-6.99 (2H, m); 7.28-7.32 (1H, m. ); 7.55-7.68 (2H, m.); 7.95-7.99 (1H, m.).

Infrared spectrum (KBr), cm ^-1 : 1740, 1720, 1510, 1410, 1280, 1255, 1145, 755, 740.

 EXAMPLE 18. 2-Butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-acetic acid.

A mixture of ethyl ether 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-acetic acid (0.28 g) in 1 N. a solution of NaOH (1.5 ml) and methanol (5 ml) was heated under reflux for 2 hours. The reaction mixture was concentrated and neutralized with 1 N. HCl solution. The separated crystals were collected by filtration and purified by chromatography on a silica gel column, whereby colorless crystals were obtained (0.12 g, 46%), melting point 170-171 ° ^C.

Elemental analysis for C ₂₇ H ₂₆ N ₆ O ₂ .

 Calculated, C 69.51; H 5.62; N, 18.01.

 Found, C, 69.60; H 5.78; N, 17.90.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.87 (3H, t.); 1.27-1.44 (2H, m.); 1.64-1.75 (2H, m.); 2.79 (2H, t.); 3.58 (2H, s.); 5.62 (2H, s.); 6.80 (2H, d.); 6.98-7.16 (4H, m.); 7.49-7.71 (5H, m.).

Infrared spectrum (KBr), cm ^-1 : 3430, 1720, 750.

 EXAMPLE 19 Sodium salt of 2-butyl-7-methoxymethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole .

A mixture of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-methoxymethylbenzimidazole (0.6 g) and trimethyltin azide (1.2 g) in toluene (12 ml) is heated under reflux in toluene (12 ml) for 3 days. The solvent is distilled off. To the residue add 1 N. HCl solution (8 ml), this mixture is stirred for some time, and then extracted with ethyl acetate. The organic layer was washed with water and dried, after which the solvent was distilled off. The residue was purified by silica gel column chromatography to give an oil. This product was dissolved in ethyl acetate and a methanol solution of 2-ethylhexanoic acid sodium salt (0.25 g) was added. This mixture is concentrated. The isolated crystals are recrystallized from a mixture of toluene and ethyl acetate, resulting in colorless crystals (0.22 g, 31%), melting point 175-178 ^about C.

Elemental analysis for C ₂₇ H ₂₇ N ₆ ONa · H ₂ O.

 Calculated, C 65.84; H 5.93; N, 17.06.

 Found, C, 65.94; H 5.81; N, 17.06.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.70 (3H, t); 1.06-1.25 (2H, m.); 1.50-1.65 (2H, m.); 2.49 (2H, t.); 2.86 (3H, s.); 4.21 (2H, s.); 5.27 (2H, s.); 6.41 (2H, d.); 6.73-6.77 (3H, m.); 6.92-7.00 (2H, m.); 7.19-7.30 (2H, m.); 7.37 (1H, d.); 7.62 (1H, d.).

Infrared spectrum (KBr), cm ^-1 : 1510, 1455, 1420, 1405, 1350, 1280, 1080, 740.

 EXAMPLE 20 2-Butyl-7-methoxy-1- [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole hydrochloride.

A mixture of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-methoxybenzimidazole (0.8 g) and trimethyltin azide (1.6 g) in toluene (15 ml) is heated under reflux in for 44 hours. Isolated crystals were collected by filtration and dissolved in methanol (20 ml). To this solution is added 1 N. HCl solution (8 ml), after which this mixture was stirred at room temperature for 5 minutes. Water was added to the reaction mixture, and then extracted with ethyl acetate. The organic layer was washed with water and dried. The solvent was distilled off, and the residue was purified by silica gel column chromatography to give crude crystals. Recrystallization from a mixture of ethyl acetate and methanol allowed to obtain colorless prisms (0.83 g, 87%), melting point 189-190 ^about C.

Elemental analysis for C ₂₆ H ₂₆ N ₆ O · HCl
Calculated, C 65.75; H 5.73; N, 17.69.

 Found, C, 65.46; H 5.85; N, 17.44.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.87 (3H, t.); 1.26-1.44 (2H, m.) 1.61-1.76 (2H, m.); 3.14 (2H, t.); 3.83 (3H, s.); 5.82 (2H, s.); 7.07-7.18 (5H, m.); 7.38 (1H, d.); 7.45-7.73 (5H, m.).

Infrared spectrum (KBr), cm ^-1 : 1615, 1550, 1490, 1455, 1440, 1355, 1275, 1260, 1130, 1100, 1060, 990, 870, 850, 775, 750, 730.

 EXAMPLE 21. 2-Butyl-6-methyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7 -carboxylic acid.

A mixture of ethyl 2-butyl-6-methyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (0.55 g) in 5 n . an aqueous solution of sodium hydroxide (5 ml) and ethanol (10 ml) is heated under reflux for 100 hours. The reaction mixture is concentrated to dryness, dissolved in water and this solution is acidified with concentrated HCl. The precipitates isolated are collected by filtration and washed with a mixture of dichloromethane and methanol. Precipitation is dissolved in saturated aqueous sodium bicarbonate. After removal of insoluble materials by filtration, the filtrate was acidified with concentrated HCl. The precipitates were collected by filtration and crystallized from a mixture of dimethylformamide and water to give colorless crystals (0.22 g, 42%), melting point 298-299 ° ^C.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.85 (3H, t); 1.23-1.43 (2H, m.); 1.58-1.75 (2H, m.); 2.38 (3H, s.); 2.70 (2H, t.); 5.47 (2H, s.); 6.87, 7.02 (each 2H, d.); 7.07 (1H, d.); 7.45-7.71 (5H, m.).

Elemental analysis for C ₂₇ H ₂₆ N ₆ O ₂ · 1 / 10H ₂ O.

 Calculated, C 69.24.

 Found, C, 68.97; H 5.85; N, 17.81.

 EXAMPLE 22. 2-Butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] -7-methylbenzimidazole.

A mixture of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-methylbenzimidazole (0.5 g), sodium azide (1.3 g) and ammonium chloride (1.1 g) in dimethylformamide (5 ml) was stirred at a temperature of 110-120 ^about C for 3.5 days. Water was added to the reaction mixture and acidified (pH 3-4) 1 N. HCl solution and then extracted with ethyl acetate. The organic layer was washed with water and dried. The solvent was distilled off, and the residue was purified by silica gel column chromatography to give crystals. Recrystallization from a mixture of ethyl acetate and methanol allowed to obtain colorless crystals (0.36 g, 62%), melting point 222-224 ^about C.

Elemental analysis for C ₂₆ H ₂₆ N ₆ · 1 / 4C ₄ H ₈ O ₂ .

 Calculated, C 72.95; H 6.35; N, 18.90.

 Found, C, 72.80; H 6.35; N, 19.02.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.80 (3H, t); 1.14-1.32 (2H, m.); 1.44-1.59 (2H, m.); 2.14 (2H, t.); 2.26 (3H, s.); 5.32 (2H, s.); 6.48-6.56 (3H, m.); 6.83-6.89 (4H, m.); 7.29-7.34 (1H, m.); 7.55-7.68 (2H, m.); 7.92-7.97 (1H, m.).

Infrared spectrum (KBr), cm ^-1 : 1510, 1450, 1410, 780, 750, 740.

 EXAMPLE 23 2-Isopropyl-1 - [[2'- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid ethyl ester acids.

A mixture of 1 - [(2'-cyanobiphenyl-4-yl) methyl] -2-isopropylbenzimidazole-7-carboxylic acid ethyl ester (2.12 g), sodium azide (3.9 g) and ammonium chloride (3.2 g ) in dimethylformamide (15 ml) was stirred at 110-120 ^about C for 5 days. Water (150 ml) was added to the reaction mixture and acidified (pH 3-4) with dilute hydrochloric acid, and then extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated to dryness. The concentrate is crystallized from ethanol with the formation of colorless prisms (1.2 g, 52%), melting point 144-146 ^about C.

Elemental analysis for C ₂₇ H ₂₆ N ₆ O ₂ · 1 / 4C ₂ H ₅ OH · H ₂ O.

 Calculated, C 66.58; H 5.99; N, 16.94.

 Found, C, 66.38; H 5.74; N, 16.69.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ -CF ₃ COOH) δ: 1.30 (3H, t); 1.53 (6H, d.); 3.37-3.80 (1H, m.); 4.30 (2H, q); 5.97 (2H, s.); 6.90 (2H, d.); 7.13 (2H, d.); 7.43-8.10 (7H, m.).

Infrared spectrum (nujol), cm ^-1 : 1730, 1450, 1285, 1270, 750.

 EXAMPLE 24 2-Methyl-1 - [[2'- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid ethyl ester acids.

A mixture of 1 - [(2'-cyanobiphenyl-4-yl) methyl] -2-methylbenzimidazole-7-carboxylic acid ethyl ester (2.5 g), sodium azide (3.9 g) and ammonium chloride (3.2 g ) in dimethyl foramide (30 ml) was stirred at 110-120 ^about C for 4 days. The reaction mixture was worked up in accordance with the procedure described in working example 23, whereby crystals were obtained. Recrystallization from ethanol led to the formation of colorless prisms (1.36 g. 49%), melting point 205-206 ^about C.

Elemental analysis for C ₂₅ H ₂₂ N ₆ O ₂ · 2/5 ethanol.

 Calculated, C 67.82; H 5.38; N, 18.39.

 Found, C, 67.64; H 5.38; N, 18.24.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ -CF ₃ COOH) δ: 1.27 (4H, t); 2.90 (3H, s.); 3.87 (1H, q); 4.30 (2H, q); 5.93 (2H, s.); 6.93 (2H, d.); 7.10 (2H, d.); 7.40-7.80 (5H, m.); 8.00 (2H, d.).

Infrared spectrum (nujol), cm ^-1 : 1725, 1410, 1290, 1260, 1220, 1115, 1040, 750.

 EXAMPLE 25. Ethyl 2-ethyl-1 - [[2'- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carbon acids.

A mixture of 1 - [(2'-cyanobiphenyl-4-yl) methyl] -2-ethylbenzimidazole-7-carboxylic acid ethyl ester (1.55 g); Sodium azide (2.6 g) and ammonium chloride (2.14 g) in dimethylformamide (15 ml) was stirred at 110-120 ^C for 5 days. The reaction mixture was worked up in accordance with the procedure described in working example 23, whereby crystals were obtained. Recrystallization from ethanol led to the formation of colorless prisms (0.68 g, 40%), melting point 188-189 ^about C.

Elemental analysis for C ₂₆ H ₂₄ N ₆ O ₂ · 2 / 5H ₂ O.

 Calculated, C 67.93; H 5.44; N, 18.28.

 Found, C, 67.76; H 5.36; N, 18.54.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ -CF ₃ COOH) δ: 1.33 (3H, t); 1.50 (3H, t.); 3.27 (2H, q); 4.33 (2H, q); 5.97 (2H, s.); 6.93 (2H, d.); 7.17 (2H, d.); 7.40-8.07 (7H, m.).

Infrared spectrum (nujol), cm ^-1 : 1710, 1285, 1265, 755.

 EXAMPLE 26. 2-Methyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

2-methyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid ethyl ester (0.64 g) was heated under reflux for 4 hours in a mixture of methanol (10 ml) and 2 N. NaOH solution. The reaction mixture was concentrated to dryness, the concentrate was dissolved in water, and then neutralized with 1 N. HCl solution to form crystals. Recrystallization from a mixture of dimethylformamide, ethanol and water afforded colorless prisms (0.3 g, 49%), temperature 283-284 ^{° C} (decomposition).

Elemental analysis for C ₂₃ H ₁₈ N ₆ O ₂ · 1 / 5H ₂ O.

 Calculated, C 66.72; H 4.48; N, 20.30.

 Found, C, 66.96; H 4.40; N, 20.25.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ -CF ₃ COOH) δ: 2.97 (3H, s); 5.97 (2H, s.); 6.97 (2H, d.); 7.17 (2H, d.); 7.50-7.90 (5H, m.); 8.10 (1H, d.); 8.20 (1H, d.).

Infrared spectrum (nujol), cm ^-1 : 2470, 1700, 1455, 1410, 1240, 1220, 990, 750.

 EXAMPLE 27. 2-Ethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

A mixture of ethyl 2-ethyl-1-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (0.5 g) in methanol (10 ml ) and 2 N. NaOH solution was refluxed for 4 hours. The reaction mixture was concentrated to dryness. The concentrate is dissolved in water and then neutralized 1 N. HCl solution to form crystals. Recrystallization from a mixture of dimethylformamide, ethanol and water allowed to obtain colorless prisms (0.27 g, 58%), melting point 261-262 ^about C.

Elemental analysis for C ₂₄ H ₂₀ N ₆ O ₂ .

 Calculated, C 67.63; H 4.70; N, 19.45.

 Found, C, 67.91; H 4.75; N, 19.80.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ -CF ₃ COOH) δ: 1.50 (3H, t); 3.20 (2H, q); 5.97 (2H, s.); 6.93 (2H, d.); 7.13 (2H, d.); 7.37-8.17 (7H, m.).

Infrared spectrum (nujol), cm ^-1 : 3070, 2720, 1700, 1450, 1410, 1290, 1250, 1210, 755.

 EXAMPLE 28. 2-Isopropyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

A mixture of 2-isopropyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid ethyl ester (1.2 g) in methanol (5 ml) and 2 n. NaOH solution (5 ml) was heated under reflux for 4 hours. The reaction mixture was concentrated to dryness, dissolved in water, and then neutralized with 1N HCl solution to form crystals. Recrystallization from a mixture of dimethylformamide and 50% ethanol afforded colorless prisms (0.8 g, 71%), melting point 265-267 ^C (decomposition).

Elemental analysis for C ₂₅ H ₂₂ N ₆ O ₂ · 3 / 10H ₂ O.

 Calculated, C 67.65; H 5.13; N, 18.93.

 Found, C, 67.64; H 5.07; N, 19.00.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ -CF ₃ COOH) δ: 1.67 (6H, d); 3.40-3.83 (1H, m.); 6.00 (2H, s.); 6.90 (2H, d.); 7.13 (2H, d.); 7.43-7.83 (5H, m.); 8.07 (2H, d.).

Infrared spectrum (nujol), cm ^-1 : 2620, 1695, 1285, 1260, 1245, 1205, 760.

 EXAMPLE 29. 2-Potassium salt of 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7 -carboxylic acid.

To a solution of 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (1.2 g) and potassium 2-ethylhexanoate (1, 3 g) in ethanol (50 ml), toluene (50 ml) was added, and ethanol was removed by evaporation. The isolated crystals thus collected by filtration and washed with ether, whereby colorless crystals were obtained (1.1 g, 79%), melting point 355-358 ^C (decomposition).

Elemental analysis for C ₂₆ H ₂₂ K ₂ N ₆ O ₂ · H ₂ O.

 Calculated, C 57.12; H 4.42; N, 15.37.

 Found, C 56.93; H 4.26; N, 15.01.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.86 (3H, t); 1.22-1.43 (2H, m.); 1.60-1.76 (2H, m.); 2.70 (2H, t.); 6.06 (2H, s. (; 6.79 (2H, d.); 6.94-7.03 (3H, m.); 7.20-7.34 (4H, m.); 7, 40 (1H, doublet of doublets); 7.53-7.58 (1H, m.).

Infrared spectrum (KBr), cm ^-1 : 3350, 1600, 1570, 1515, 1460, 1400, 1360, 1315, 1280, 1005, 825, 785, 760.

 EXAMPLE 30. 2-Butyl-7-hydroxy-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole.

A mixture of 2-butyl-1 - [(2'-cyanobiphenyl-4-yl) methyl] -7-hydroxybenzimidazole (0.69 g) and trimethyltin azide (1.1 g) in toluene (15 ml) is heated under reflux in within 4 days. The isolated crystals are collected by filtration and stirred in a mixture of 1 N. HCl solution (10 ml) and methanol (15 ml) for 10 days at room temperature. To the resulting solution was added 1 N. NaOH solution to bring the pH to 3-4, resulting in the formation of crystals. The crude crystals are purified by chromatography on silica gel columns, which allows crystals to be obtained. Recrystallization from acetone led to the formation of colorless crystals, melting point 186-188 ^about C.

Elemental analysis for C ₂₅ H ₂₄ N ₆ O · 1 / 2H ₂ O
Calculated, C 69.27; H 5.81; N, 19.39.

 Found, C, 69.60; H, 5.69; N, 19.26.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.84 (3H, t.); 1.23-1.41 (2H, m.); 1.55-1.70 (2H, m.); 2.71 (2H, t.); 5.68 (2H, s.); 6.60 (1H, d.); 6.95 (1H, t.); 7.02-7.06 (5H, m.); 7.48-7.70 (4H, m.); 10.00 (1H, s.).

Infrared spectrum (KBr), cm ^-1 : 1620, 1490, 1460, 1350, 1295, 780, 755, 730.

 EXAMPLE 31. Methyl 2-propyl-1 - [[2'- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carbon acids.

A mixture of 2-propyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (465 mg) and concentrated sulfuric acid (7.2 g) in methanol (60 ml) was heated under reflux for 24 hours. After removal of the solvent, the residue was suspended in water and 1N was added. NaOH solution to adjust the pH to 3-4, and then extracted with ethyl acetate. The organic layer was washed with water and dried, after which the solvent was evaporated. The residue was purified by silica gel column chromatography. Recrystallization from ethanol allowed to obtain colorless prisms (310 mg), melting point 195-196 ^about C.

Elemental analysis for C ₂₆ H ₂₄ N ₆ O ₂ · 2 / 5H ₂ O
Calculated, C 67.93; H 5.44; N, 18.28.

 Found, C, 68.02; H 5.33; N, 18.33.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.87 (3H, t); 1.37-1.80 (2H, m.); 2.30 (2H, t.); 3.60 (3H, s.); 5.47 (2H, s.); 6.47 (2H, d.); 6.80 (2H, d.); 6.93-8.00 (7H, m.).

Infrared spectrum (nujol), cm ^-1 : 1730, 1440, 1290, 1230, 1270, 760.

 The following compounds (working examples 32-33) were obtained in accordance with the procedure described in working example 5.

 EXAMPLE 32. 2-Ethyl-1 methyl ester - [[2'- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carbon acids.

Melting point 185-186 ^about C.

Elemental analysis for C ₂₅ H ₂₂ N ₆ O ₂ · 1 / 2C ₄ H ₈ O ₂ · H ₂ O.

 Calculated, C 66.70; H 5.47; N, 17.29.

 Found, C, 66.70; H 4.26; N, 17.49.

 EXAMPLE 33. 2-Isopropyl-1- [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic methyl ester acids.

 EXAMPLE 34. 2-Butyl-1 methyl ester - [[2'- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carbon acids.

A mixture of 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (1.8 g) in methanol (18 ml) and concentrated sulfuric acid acid (14.4 g) is heated under reflux for 24 hours. After removal of the solvent by evaporation, the residue is suspended in water, the pH of which is adjusted to 3-4 with 1 N. NaOH solution and then extracted with ethyl acetate. The organic layer was washed with water and dried. The solvent was removed by evaporation, and the residue was purified by silica gel column chromatography. Recrystallization from ethanol allowed to obtain colorless prisms (1.05 g), melting point 153-155 ^about C.

Elemental analysis for C ₂₇ H ₂₆ N ₆ O ₂ · 2 / 5H ₂ O.

 Calculated, C 68.45; H 5.70; N, 17.74.

 Found, C, 68.63; H 5.61; N, 17.72.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.80 (3H, t); 1.00-1.73 (4H, m.); 2.37 (2H, t.); 3.60 (3H, s.); 5.47 (2H, s.); 6.47 (2H, d.); 6.80 (2H, d.); 6.97-8.00 (7H, m.).

Infrared spectrum (nujol), cm ^-1 : 1720, 1450, 1430, 1290, 1280, 1270, 755.

 EXAMPLE 35. Ethyl 2-sec-butyl-1- [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7 - carboxylic acid.

 This compound is obtained in accordance with the procedure described in working example 14.

Melting point 128-130 ^about C.

Elemental analysis for C ₂₈ H ₂₈ N ₆ O ₂ · 2 / 5C ₄ H ₈ O ₂ · 2 / 5H ₂ O.

 Calculated, C 67.98; H, 6.06; N, 16.07.

 Found, C, 68.10; H, 6.07; N, 15.94.

 EXAMPLE 36. 2-Butyl-1-pivaloyloxymethyl ester - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole 7-carboxylic acid .

Solution of 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (3.0 g), triphenylmethyl chloride (1.96 g) and triethylamine (1.0 ml) in methylene chloride (20 ml) was stirred at room temperature for 16 hours. The reaction mixture was washed with water and dried. After removing the solvent, the residue was purified by silica gel column chromatography to give a colorless powder (4.25 g). The N-trityl compound thus obtained was dissolved in dimethylformamide (5 ml). Potassium carbonate (0.2 g) and pivaloyloxymethyl iodide (0.35 g) were added to this solution, after which the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated. Water and ethyl acetate were added to the concentrate, and then extracted. The organic layer was washed with water and dried. After removal of the solvent by evaporation, the residue was dissolved in methanol (10 ml). To the solution is added 1 N. HCl solution (3 ml), after which the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated to dryness and the concentrate was purified by silica gel column chromatography to give colorless powder crystals (0.43 g, 74% ), melting point 102-105 ^about C.

Elemental analysis for C ₃₂ H ₃₄ N ₆ O ₄ · 1 / 2H ₂ O.

 Calculated, C 66.77; H, 6.13; N, 14.60.

 Found, C, 66.76; H 6.09; N, 14.45.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.87 (3H, t); 1.16 (9H, s.); 1.23-1.42 (2H, m.); 1.57-1.72 (2H, m.); 2.53 (2H, t.); 5.60 (2H, s.); 5.70 (2H, s.); 6.60 (2H, d.); 6.89 (2H, d.); 7.11 (1H, t.); 7.25-7.27 (1H, m.); 7.33-7.38 (1H, m.); 7.58-7.63 (3H, m.); 7.97-8.02 (1H, m.).

Infrared spectrum (KBr), cm ^-1 : 2975, 1750, 1730, 1480, 1450, 1410, 1280, 1260, 1150, 1100, 1010, 950, 760, 750.

 In accordance with the method presented in working example 36, the following compounds were obtained.

 EXAMPLE 37. 1- (Cyclohexyloxycarbonyloxy) ethyl ester 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Yield 74%
Melting point 102-105 ^about C.

Elemental analysis for C ₃₅ H ₃₈ N ₆ O ₅ · 1 / 5CHCl ₃ .

 Calculated, C 65.39; H 5.95; N, 13.00.

 Found, C, 65.18; H 5.99; N, 12.86.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.87 (3H, t); 1.17-1.87 (18H, m.); 2.53 (2H, t.); 4.45-4.58 (1H, m.); 5.52-5.75 (2H, m.); 6.60 (2H, d.); 6.73 (1H, q); 6.89 (2H, d.); 7.12 (1H, t.); 7.27-7.35 (2H, m.); 7.57-7.66 (3H, m.); 7.98-8.08 (1H, m.).

Infrared spectrum (KBr), cm ^-1 : 2950, 2875, 1760, 1740, 1450, 1420, 1280, 1250, 1080, 1000, 910, 760.

 EXAMPLE 38. 1- (Ethoxycarbonyloxy) ethyl 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Yield 75%
Melting point 92-95 ^about C.

Elemental analysis:
Calculated, C 64.46; H 5.76; N, 14.55.

 Found, C, 64.56; H, 5.69; N, 14.52.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.86 (3H, t); 1.21 (3H, t.); 1.27-1.43 (2H, m.); 1.42 (3H, d.); 1.46-1.69 (2H, m.); 2.50 (2H, t.); 4.13 (2H, double quartet); 5.48-5.73 (2H, m.); 5.56 (2H, d.); 6.72 (1H, q); 6.86 (2H, d.); 7.09 (1H, t.); 7.19-7.23 (1H, m.); 7.29-7.34 (1H, m.); 7.55-7.64 (3H, m.); 7.97-8.01 (1H, m.).

Infrared spectrum (KBr), cm ^-1 : 1760, 1730, 1410, 1375, 1275, 1245, 1070, 990, 760.

 EXAMPLE 39. (5-Methyl-2-oxo-1,3-dioxolen-4-yl) methyl ester 2-butyl-1 - [[2 '- (1H- tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Yield 71%
Melting point 123-125 ^about C.

Elemental analysis for C ₃₁ H ₂₈ N ₆ O ₅ · 1 / 2H ₂ O.

 Calculated, C 64.91; H 5.10; N, 14.65.

 Found, C 64.79; H 4.82; N, 14.34.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.84 (3H, t); 1.22-1.40 (2H, m.); 1.53-1.68 (2H, m.); 2.16 (3H, s.); 2.46 (2H, t.); 4.81 (2H, s.); 5.54 (2H, s.); 6.53 (2H, d.); 6.86 (2H, d.); 7.08-7.22 (2H, m.); 7.43-7.38 (1H, m.); 7.58-7.65 (3H, m.); 7.95-8.00 (1H, multiplet).

Infrared spectrum (KBr), cm ^-1 : 1820, 1720, 1400, 1300, 1275, 1250, 1220, 1185, 1105, 1000, 745.

 EXAMPLE 40. 2-Butyl-1-hydroxyethyl ether - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazol-7 - carboxylic acid.

To a solution of ethyl 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (0.72 g) in ethylene glycol (15 ml) sodium hydride (60% oil, 0.25 g) was added, stirring at room temperature, after which the mixture was stirred at room temperature for 15 hours. A mixture of ice water (100 ml) was added to the reaction mixture and acidified with formic acid. The precipitates formed are dissolved in ethyl acetate (100 ml), the solution is washed with water, dried and concentrated to dryness to form a crystalline product. These crystals are recrystallized from acetone, resulting in colorless crystals (0.49 g, 68%), melting point 145-147 ^about C.

Elemental analysis for C ₂₈ H ₂₈ N ₆ O ₃ · 1/2 C ₃ H ₆ O
Calculated, C 67.41; H 5.94; N, 15.99.

 Found, C, 67.19; H 5.84; N, 15.79.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.93 (3H, t); 1.23-1.97 (4H, m.); 2.13 (3H, s.); 2.87 (2H, t.); 3.77 (2H, t.); 4.23 (2H, t.); 5.73 (2H, s.); 6.77 (2H, d.); 7.00 (2H, d.); 7.20 (1H, t.); 7.43-7.93 (6H, m.).

Infrared spectrum (nujol), cm ^-1 : 3340, 1715, 1410, 1290, 1265, 1035, 755.

 EXAMPLE 41. 2- (4-Morpholino) ethyl 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

To a cold solution of 2-butyl-1 - [[2 '- (N-triphenylmethyltetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (0.4 g), 4- (2-hydroxyethyl ) morpholine (0.15 g) and phosphocyanic acid diethyl ether (0.1 g) in dimethylformamide (2 ml) add a solution of triethylamine (0.06 g) in dimethylformamide (1 ml), after which the mixture is stirred at room temperature for 30 h. The reaction mixture was concentrated to dryness to form a residue, which was purified by chromatography on silica gel columns, resulting in a colorless solid. powder (0.3 g, 65%). This product was dissolved in methanol (7 ml) and 1N was added to this solution. HCl solution (1.2 ml). After stirring at room temperature for 2 hours, the reaction solution was concentrated to dryness to form a residue. This residue was dissolved in CH ₂ Cl ₂ —H ₂ O and the aqueous layer was made basic with an aqueous solution of NaHCO ₃ . The aqueous layer was extracted with CH ₂ Cl ₂ , the combined CH ₂ Cl ₂ solution was washed with water, dried and evaporated to dryness, which allowed to obtain a residue. This residue was purified by chromatography on a silica gel column to give colorless fine crystals (0.19 g, 87%), melting point 98-110 ° ^C.

Elemental analysis for C ₃₂ H ₃₅ N ₇ O ₃ · 3 / 5H ₂ O.

 Calculated, C 66.67; H 6.33; N, 17.01.

 Found, C, 66.41; H, 6.15; N, 16.89.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.93 (3H, t); 1.34-1.52 (2H, m.); 1.71-1.88 (2H, m.); 2.58 (4H, broad triplet); 2.85 (2H, t.); 2.94 (2H, broad triplet); 3.39 (2H, broad triplet); 4.10 (2H, broad triplet); 5.65 (2H, s.); 6.63 (2H, d.); 6.96 (2H, d.); 7.25 (1H, t.); 7.40-7.61 (4H, m.); 7.77 (1H, doublet of doublets); 7.83 (1H, d.).

 The following compounds (working examples 42 and 43) were obtained in accordance with a method similar to that described in working example 41.

 EXAMPLE 42. 2- (1-Piperidino) ethyl ester 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Colorless powder (55%), melting point 210-213 ^about C.

Elemental analysis for C ₃₃ H ₃₇ N ₇ O ₂ · 3 / 5H ₂ O.

 Calculated, C 68.99; H, 6.70; N, 17.07.

 Found, C, 68.93; H 6.59; N, 16.94.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.96 (3H, t); 1.27-1.58 (8H, m.); 1.79-1.94 (2H, m.); 2.72-2.85 (4H, m.); 2.93 (2H, t.); 3.20-3.31 (2H, m.); 4.10-4.27 (2H, m.); 5.63 (2H, broad singlet); 6.59-6.70 (2H, m.); 7.04 (2H, d.); 7.26 (2H, t.); 7.36-7.50 (4H, m.); 7.72-7.77 (1H, m.); 7.98 (1H, doublet of doublets).

 EXAMPLE 43. 2- (Dimethylamino) ethyl ester 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Colorless powder (91%), melting point 206-208 ^about C.

Elemental analysis for C ₃₀ H ₃₃ N ₇ O ₂ · 2.1H ₂ O.

 Calculated, C 64.18; H 6.68; N, 17.46.

 Found, C, 64.31; H 6.40; N, 17.16.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.96 (3H, t); 1.39-1.57 (2H, m.); 1.79-1.94 (2H, m.); 2.34 (6H, s.); 2.94 (2H, t.); 3.10 (2H, broad triplet); 4.19 (2H, broad triplet); 5.66 (2H, s.); 6.63 (2H, d.); 7.03 (2H, d.); 7.27 (1H, t.); 7.39-7.54 (4H, m.); 7.73-7.78 (1H, m.); 7.97 (1H, doublet of doublets).

 EXAMPLE 44. Methyl 2-methoxymethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carbon acids.

A mixture of 1 - [(2'-cyanobiphenyl-4-yl) methyl] -2-methoxymethylbenzimidazole-7-carboxylic acid methyl ester (0.4 g) and trimethyltin azide (1.0 g) in toluene (10 ml) heated under reflux for 49 hours. The reaction solution was concentrated to dryness to form a residue, after which this residue was dissolved in methanol (6 ml) and 1 N. HCl solution (6 ml). The solution was stirred for 3 hours and concentrated to dryness to form a residue. This residue was dissolved in CH ₂ Cl ₂ H ₂ O and the mixture was neutralized with 1N. NaOH solution. The organic layer was washed with water, dried and concentrated to dryness to form a residue, which was purified by silica gel column chromatography to give a crystalline product.

 Recrystallization from a mixture of ethyl acetate and isopropyl ether resulted in the formation of colorless needles (0.3 N, 68%).

Melting point 191-194 ^about C.

Elemental analysis for C ₂₅ H ₂₂ N ₆ O ₃ · 3 / 5H ₂ O.

 Calculated, C 64.53; H 5.03; N, 18.06.

 Found, C, 64.57; H 4.94; N, 17.97.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 3.27 (3H, s.); 3.66 (3H, s.); 4.21 (2H, s.); 5.62 (2H, s.); 6.59 (2H, d.); 6.87 (2H, d.); 7.16 (1H, t.); 7.30-7.36 (2H, m.); 7.55-7.63 (3H, m.); 7.93-7.99 (1H, m.).

 The following compounds (working examples 45-47) were obtained in accordance with a method similar to that described in working example 44.

 EXAMPLE 45. 2-Ethoxymethyl-1- [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid ethyl ester acids.

 Colorless powder.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 1.14 (3H, t); 1.21 (3H, t.); 3.45 (2H, q); 4.20 (2H, q); 4.85 (2H, s.); 5.89 (2H, s.); 6.95 (2H, d.); 7.10-7.40 (3H, m.); 7.56-7.70 (3H, m.); 7.96 (1H, doublet of doublets).

 EXAMPLE 46. Ethyl 2-ethylthiomethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-ka rbonic acid.

 Colorless powder.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 1.12 (3H, t); 1.23 (3H, t.); 2.46 (2H, q); 4.11 (2H, q); 3.36 (2H, s.); 5.63 (2H, s.); 6.58 (2H, d.); 6.87 (2H, d.); 7.10-7.36 (3H, m.); 7.56-7.64 (3H, m.); 7.97-8.04 (1H, m.).

 EXAMPLE 47. 2-Methylthiomethyl-1- [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid ethyl ester acids.

 Colorless powder (56%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 1.21 (3H, t); 2.03 (3H, s.); 4.11 (2H, q); 5.63 (2H, s.); 6.60 (2H, d.); 6.91 (2H, d.); 7.15-7.40 (3H, m); 7.55-7.68 (3H, m.); 8.00-8.10 (1H, m.);
EXAMPLE 48. 2-Hydroxymethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid ethyl ester acids.

 This compound was prepared according to a method similar to that described in working example 44 from ethyl 2-acetoxymethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazol-7- carboxylic acid.

 Pale yellow powder (80%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 1.20 (3H, t); 4.17 (2H, q); 4.82 (2H, broad singlet); 5.56 (2H, broad singlet); 6.65 (2H, d.); 6.86 (2H, d.); 6.82-6.95 (1H, m.); 7.21-7.54 (4H, m.); 7.62 (1H, d.); 7.75-7.82 (1H, m.).

 EXAMPLE 49. 2-Methoxymethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid. 2-Methoxymethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

A solution of 2-methoxymethyl-1 methyl ester - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (0.2 g) in methanol (10 ml) and 1 n NaOH solution (1.5 ml) was heated at ⁸⁰ ° C for 20 hours. The solution was concentrated to dryness to give a residue. The residue was dissolved in water and acidified, resulting in a crystalline product. Recrystallization from a mixture of dimethylformamide, methanol and water yielded colorless prisms (0.16 g, 80%).

Melting point 272-274 ^about C.

Elemental analysis for C ₂₄ H ₂₀ N ₆ O ₃ (molecular weight 440.46).

 Calculated, C 6.5; H 4.58; N, 19.08.

 Found, C, 65.32; H 4.47; N, 18.95.

Spectrum 1 ^H- NMR (200 Hz, DMSO-d ₆ ) δ: 3.28 (3H, s.); 4.68 (2H, s.); 5.87 (2H, s.); 6.80 (2H, d.); 6.98 (2H, d.); 7.29 (1H, t.); 7.45-7.70 (5H, m.); 7.91 (1H, doublet of doublets).

 The following compounds (working examples 50-54) were obtained in accordance with a method similar to that described in working example 49.

 EXAMPLE 50. 2-Ethoxymethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Colorless powder (80%), melting point 243-245 ^about C.

 Elemental analysis (molecular weight 463.50).

 Calculated, C 64.78; H 5.00; N, 18.13.

 Found, C, 64.99; H 4.97; N, 18.26.

Spectrum 1 ^H- NMR (200 Hz, DMSO-d ₆ ) δ: 1.01 (3H, t.); 3.48 (2H, q); 4.72 (2H, s.); 5.89 (2H, s.); 6.81 (2H, d.); 6.99 (2H, d.); 7.29 (1H, t.); 7.44-7.70 (5H, m.); 7.91 (1H, doublet of doublets).

 EXAMPLE 51. 2-Methylthiomethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Colorless powder (82%), melting point 270-272 ^about C.

Elemental analysis for C ₂₄ H ₂₀ N ₆ O ₂ S · 1 / 2H ₂ O (molecular weight 465.54).

 Calculated, C 61.92; H 4.55; N, 18.05.

 Found, C, 61.94; H 4.44; N, 18.20.

Spectrum 1 ^H- NMR (200 MHz, DSMO-d ₆ ) δ: 2.09 (3H, s.); 3.98 (2H, s.); 589 (2H, s.); 6.80 (2H, d.); 7.00 (2H, d.); 7.27 (1H, t.); 7.45-7.69 (5H, m.); 7.87 (1H, doublet of doublets).

 EXAMPLE 52. 2-Hydroxymethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Colorless powder (65%), melting point 292-294 ^about C.

Elemental analysis for C ₂₃ H ₁₈ N ₆ O ₃ · 3 / 10H ₂ O (molecular weight 431.84).

 Calculated, C 63.97; H 4.34; N, 19.46.

 Found, C, 64.01; H 4.29; N, 19.49.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 4.72 (2H, s.); 5.92 (2H, s.); 6.83 (2H, d.); 6.98 (2H, d.); 7.27 (1H, t.); 7.45-7.68 (5H, m.); 7.88 (1H, doublet of doublets).

 EXAMPLE 53. 2-Ethylthiomethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Colorless crystals (76%), melting point 157-160 ^about C.

Elemental analysis for C ₂₅ H ₂₂ N ₆ O ₂ S · 9 / 10H ₂ O.

 Calculated, C 61.69; H 4.93; N, 17.26.

 Found, C, 61.75; H 4.91; N, 17.26.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 1.18 (3H, t); 2.54 (2H, q); 4.01 (2H, s.); 5.89 (2H, s.); 6.80 (2H, d.); 7.00 (2H, d.); 7.27 (1H, t.); 7.45-7.68 (5H, m.); 7.87 (1H, doublet of doublets).

 EXAMPLE 54. 2-Methylaminomethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

 Colorless powder (48%).

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 2.66 (3H, s.); 4.42 (2H, s.); 5.84 (2H, s.); 6.79 (2H, d.); 7.00 (2H, d.); 7.27-7.68 (6H, m.); 7.87 (1H, d.).

 The following compounds (working examples 55-58) were obtained in accordance with a method similar to that described in working example 31.

 EXAMPLE 55. 2-Methylthiomethyl-1- [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic methyl ester acids.

Colorless powder (54%), melting point 186-188 ^about C.

Elemental analysis for C ₂₅ H ₂₂ N ₆ O ₂ S · 1 / 2H ₂ O.

 Calculated, C 62.61; H 4.83; N, 17.52.

 Found, C, 62.82; H 4.63; N, 17.69.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 2.03 (3H, s.); 3.70 (3H, s.); 3.36 (2H, s.); 5.63 (2H, s.); 6.64 (2H, d.); 6.94 (2H, d.); 7.18 (1H, t.); 7.30-7.40 (2H, m.); 7.57-7.66 (3H, m.); 8.02-8.07 (1H, m.).

 EXAMPLE 56. Methyl 2-ethylthiomethyl-1- [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid acids.

 Pale yellow powder (49%).

Elemental analysis for C ₂₆ H ₂₄ N ₆ O ₂ S · 1 / 2H ₂ O.

 Calculated, C 63.27; H, 5.11; N, 17.03.

 Found, C, 63.42; H 4.87; N, 16.92.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 1.09 (3H, t); 2.42 (2H, q); 3.22 (2H, s.); 3.64 (3H, s.); 5.57 (2H, s.); 6.53 (2H, d.); 6.84 (2H, d.); 7.13 (2H, d.); 7.31-7.38 (1H); 7.56-7.65 (3H, m.); 7.89-7.98 (1H, m.).

 EXAMPLE 57. 2-Hydroxymethyl-1- [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic methyl ester acids.

 Colorless powder (30%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 3.63 (3H, s.); 4.77 (2H, s.); 5.75 (2H, s.); 6.76 (2H, d.); 6.99 (2H, d.); 7.23 (1H, t.); 7.39-7.62 (5H, m.); 7.90 (1H, doublet of doublets).

 EXAMPLE 58. 2-Ethoxymethyl-1- [[2 '- (1H, tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic methyl ester acids.

Colorless needles (61%), melting point 214-217 ^о С.

Elemental analysis for C ₂₆ H ₂₄ N ₆ O ₃ · 1 / 5H ₂ O.

 Calculated, C 66.08; H 5.18; N, 17.87.

 Found, C, 66.15; H, 5.21; N, 17.80.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 1.14 (3H, t); 3.44 (2H, q); 3.68 (3H, s.); 4.13 (2H, s.); 5.63 (2H, s.); 6.61 (2H, d.); 6.89 (2H, d.); 7.16 (1H, t.); 7.19-7.39 (2H, m.); 7.57-7.64 (3H, m.); 7.97-8.02 (1H, m.).

 EXAMPLE 59. Ethyl 2-chloromethyl-1 - [[2'- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carbon acids.

To a solution of ethyl 2-hydroxymethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-arboxylic acid (0.2 g) in CH ₂ Cl ₂ ( 3 ml) thionyl chloride (0.3 ml) was added dropwise, after which this mixture was heated under reflux for 3 hours. The reaction solution was poured into ice-water, the organic layer was washed with water, dried and evaporated to dryness, as a result which obtained a pale yellow amorphous powder (0.2 g, 96%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 1.29 (3H, t); 4.19 (2H, q); 4.63 (2H, s.); 5.77 (2H, s.); 6.75 (2H, d.); 7.03 (2H, d.); 7.28 (1H, t.); 7.35-7.39 (1H, m.); 7.56-7.72 (4H, m.); 8.06-8.11 (1H, m.).

 EXAMPLE 60. Ethyl 2-methylaminomethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid acids.

To a solution of ethyl 2-chloromethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (0.2 g) in acetonitrile (5 ml) was added a solution of 40% methylamine in methanol (0.33 g), and the mixture was heated at ⁶⁰ ° C for 77 hours. the reaction solution was cooled to give pale yellow prisms (0.12 g, 61%), melting point 248 -250 ^about C.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 1.14 (3H, t); 2.62 (3H, s.); 4.16 (2H, q); 4.39 (2H, s.); 5.71 (2H, s.); 6.73 (2H, d.); 7.03 (2H, d.); 7.27-7.46 (4H, m.); 7.54-7.63 (2H, m.); 7.94 (1H, doublet of doublets).

 The following compounds (working examples 61 and 62) were obtained in accordance with a method similar to that described in working example 1.

 EXAMPLE 61. Ethyl 2-isobutyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carbon acids.

 Colorless prisms (71%).

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.87 (6H, d); 1.13 (3H, t.); 1.23 (1H, t.); 1.83-2.40 (1H, m.); 2.00 (1H, s.); 2.27 (2H, d.); 4.03 (2H, q); 4.13 (1H, q); 5.47 (2H, s.); 6.43 (2H, d.); 6.73 (2H, d.); 6.87-7.70 (6H, m.); 7.90-8.00 (1H, m.).

 EXAMPLE 62. Ethyl ester 2-sec-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7 -carboxylic acid.

Colorless prisms (43%), melting point 128-130 ^о С.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 0.87 (3H, t); 1.00-1.17 (6H, m.); 1.23 (1H, t.); 1.50-1.90 (2H, m.); 2.03 (1H, s.); 2.63-3.03 (1H, m.); 4.00 (2H, q); 4.13 (1H, q); 5.57 (1H, d.); 5.77 (1H, d.); 6.50 (2H, d.); 6.77 (2H, d.).

Infrared spectrum (nujol), cm ^-1 : 2720, 1730, 1450, 1280, 1265, 1200, 760, 765.

 The following compounds (working examples 63 and 64) were obtained in accordance with a method similar to that described in working example 49.

 EXAMPLE 63. 2-Isobutyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Colorless powder (62%), melting point 205-207 ^C (decomposition).

Elemental analysis for C ₂₆ H ₂₄ N ₆ O ₂ · 2 / 5H ₂ O.

 Calculated, C 67.93; H 5.44; N, 18.23.

 Found, C, 67.98; H 5.63; N, 18.43.

Spectrum 1 ^H- NMR (90 MHz, CDCl ₃ ) δ: 1.57 (6H, d); 3.40-3.83 (1H, m.); 6.00 (2H, s.); 6.90 (2H, d.); 7.13 (2H, d.); 7.43-7.83 (5H, m.); 7.97-8.12 (2H, m.).

Infrared spectrum (nujol), cm ^-1 : 2460, 1690, 1410, 1290, 1245, 1200, 1120, 760.

 EXAMPLE 64. 2-Sec-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Colorless prisms (79%), melting point 184-186 ^о С.

Elemental analysis for C ₂₆ H ₂₄ N ₆ O ₂ · 1/2 ethanol.

 Calculated, C 68.20; H 5.72; N, 17.67.

 Found, C, 67.96; H 5.71; N, 17.46.

Spectrum 1 ^H- NMR (90 MHz, DMSO-d ₆ ) δ: 0.83 (3H, t.); 1.17 (1H, t.); 1.30 (3H, d.); 1.53-2.13 (2H, m.); 2.77-3.13 (1H, m.); 3.63 (1H, q); 5.90 (2H, s.); 6.80 (2H, d.); 7.03 (2H, d.); 7.23 (1H, t.); 7.33-7.97 (7H, m.).

Infrared spectrum (nujol), cm ^-1 : 2600, 1700, 1450, 1410, 1275, 1230, 1200, 1140, 750.

 The following compounds (working examples 65 and 66) were obtained in accordance with a method similar to that described in working example 19.

 EXAMPLE 65. Methyl 2- (2-methoxyethyl) - 1 - [[2 '- (2H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole -7-carboxylic acid.

 Pale yellow powder (35%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 2.60 (2H, t); 3.61 (2H, t.); 3.19 (3H, t.); 3.63 (3H, t.); 5.60 (2H, s.); 6.56 (2H, d.); 6.85 (2H, d.); 7.07-7.12 (2H, m.); 7.30-7.35 (1H, m.); 7.51-7.65 (3H, m.); 7.96 (1H, doublet of doublets).

 EXAMPLE 66. Methyl 2- (2-methylthioethyl) -1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole -7-carboxylic acid.

 Pale yellow powder (16%).

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 2.09 (3H, t), 3.63 (3H, s); 2.72-2.96 (4H, m.); 5.65 (2H, s.); 6.60 (2H, d.); 6.87 (2H, d.); 7.06-7.20 (2H, m.); 7.29-7.34 (1H, m.); 7.54-7.63 (3H, m.); 7.99-8.05 (1H, m.).

 EXAMPLE 67. 2-Butyl-1- [[2 '- (1-methyltetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic methyl ester acids and 2-butyl-1 - [[2 '- (2-methyltetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid methyl ester.

Mixture of 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (2.0 g), NaHCO ₃ (1.1 g ) and methyl iodide (1.5 g) in dimethylformamide (10 ml) was stirred at room temperature for 15 hours. The reaction mixture was diluted with water and then extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated to dryness. The resulting residue was purified by silica gel column chromatography to give a 1-methyl derivative (0.95 g, 45%) and a 2-methyl derivative (0.36 g, 17%).

1-methyl derivative (67a):
Melting point 200-201 ^about C.

Elemental analysis for C ₂₈ H ₂₈ N ₆ O ₂ .

 Calculated, C 69.98; H 5.87; N, 17.49.

 Found, C 69.67; H 5.80; N, 17.36.

Spectrum 1 ^H- NMR 200 MHz, CDCl ₃ ) δ: 0.97 (3H, t); 1.39-1.58 (2H, m.); 1.81-1.97 (2H, m.); 2.91 (2H, t.); 3.16 (3H, s.); 3.74 (3H, s.); 5.72 (2H, s.); 6.77 (2H, d.); 7.00 (2H, d.); 7.25 (1H, t.); 7.48-7.69 (5H, m.); 7.95 (1H, doublet of doublets).

Infrared spectrum (pure), cm ^-1 : 1725, 1520, 1460, 1435, 1400, 1360, 1280, 1265, 1220, 1200, 1125, 760.

 EXAMPLE 68. 2-Butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] -7-formylaminobenzimidazole and 2- butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] -7-ethoxycarbonylaminobenzimidazole.

 Mixture of 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (0.94 g), diphenylphosphoryl azide (0.61 g) and triethylamine (0.61 g) in dimethylformamide (6 ml) was stirred at room temperature for 7 hours, after which the reaction mixture was concentrated to dryness to form a crystalline residue. This residue was chromatographed on a silica gel column, which allowed two colorless crystalline products to be obtained (68a and 68b).

Formylamine derivative (68a):
Colorless crystals (0.26 g, 29%), melting point 290-292 ^C (decomposition).

Elemental analysis for C ₂₆ H ₂₅ N ₇ O.

 Calculated, C 69.16; H 5.58; N, 21.71.

 Found, C, 69.29; H 5.51; N, 21.94.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.84 (3H, t); 1.22-1.40 (2H, m.); 1.56-1.71 (2H, m.); 2.70 (2H, t.); 5.55 (2H, s.); 6.79 (16, d); 6.89 (2H, d.); 6.98-7.07 (3H, m.); 7.43 (2H, d.); 7.51-7.70 (3H, m.); 8.27 (1H, m.).

Infrared spectrum (KBr), cm ^-1 : 3340, 1630, 1530, 1510, 1420, 1400, 750, 730.

Ethoxycarbonylamino derivative (68b):
Colorless crystals (0.31 g, 31%); melting point 190-194 ^about With (decomposition).

Elemental analysis for C ₂₈ H ₂₉ N ₇ O ₂ · 0.1 H ₂ O.

 Calculated, C 67.62; H 5.92; N, 19.71.

 Found, C, 67.43; H 5.81; N, 19.70.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.87 (3H, t); 1.18 (3H, t.); 1.25-1.39 (3H, m.); 1.56-1.71 (2H, m.); 2.50 (2H, t.); 3.99 (2H, q); 5.37 (2H, s.); 6.07 (1H, s.); 6.66 (2H, d.); 6.90-7.05 (5H, m.); 7.34 (1H, doublet of doublets); 7.55-7.64 (2H, m.); 8.00 (1H, doublet of doublets).

Infrared spectrum (KBr), cm ^-1 : 1700, 1520, 1250, 750.

 EXAMPLE 69. 2-Butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] -7- (N, N dimethylaminomethyl) benzimidazole.

 This compound was obtained by a method similar to that described in working example 44.

Colorless crystals (56%), melting point 178-180 ^o C (decomposition).

Elemental analysis for C ₂₈ H ₃₁ N ₇ · 2HCl · 2H ₂ O · 1/2 ethyl acetate.

 Calculated, C 58.25; H 6.68; N, 15.85.

 Found, C, 58.42; H 6.42; N, 15.61.

Spectrum 1 ^H- NMR (200 MHz, DMSO-d ₆ ) δ: 0.91 (3H, t.); 1.33-1.51 (2H, m.); 1.71-1.86 (2H, m.); 2.50 (6H, s.); 3.17 (2H, t.); 4.32 (2H, s.); 5.92 (2H, s.); 7.07 (2H, d.); 7.14 (2H, d.); 7.49-7.72 (5H, m.); 7.80 (1H, d.); 7.92 (1H, d.).

Infrared spectrum (KBr), cm ^-1 : 3400, 1500, 1470, 1435, 1420, 750.

 The following compounds (working examples 70 and 71) were obtained by a method similar to that described in working example 44.

 EXAMPLE 70. 2-Butyl-1 - [[2 '- (1-methyltetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Colorless prisms (78%), melting point 213-214 ^о С.

Elemental analysis for C ₂₇ H ₂₆ N ₆ O ₂ · 1 / 2H ₂ O
Calculated, C 68.19; H 5.72; N, 17.67.

 Found, C, 68.52; H 5.55; N, 17.62.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.95 (3H, t); 1.38-1.57 (2H, m.); 1.80-1.95 (2H, m.); 2.99 (2H, t.); 3.18 (3H, s.); 5.82 (2H, s.); 6.80 (2H, d.); 6.97 (2H, d.); 7.27 (1H, t.); 7.48-7.68 (4H, m.); 7.80 (1H, d.); 7.98 (1H, d.).

Infrared spectrum (KBr), cm ^-1 : 1700, 1520, 1470, 1445, 1435, 1410, 1290, 1280, 1230, 1185, 1145, 1120, 1100, 820, 770, 760, 745, 730.

 EXAMPLE 71. 2-Butyl-1 - [[2 '- (2-methyltetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

Colorless needles (71%), melting point 226-228 ^о С (decomposition).

Elemental analysis for C ₂₇ H ₂₆ N ₆ O ₂ ·, 7H ₂ O.

 Calculated, C 67.68; H 5.76; N, 17.54.

 Found, C, 67.48; H 5.51; N, 17.26.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.94 (3H, t); 1.38-1.56 (2H, m.); 1.79-1.94 (2H, m.); 3.07 (2H, t.); 4.22 (3H, s.); 5.84 (2H, s.); 6.81 (2H, d.); 7.06 (2H, d.); 7.25-7.55 (4H, m.); 7.74 (1H, d.); 7.81 (1H, doublet of doublets); 8.00 (1H, d.).

Infrared spectrum (KBr), cm ^-1 : 1700, 1510, 1450, 1430, 1410, 1360, 1290, 1240, 1190, 1150, 1120, 1100, 1080, 1035, 1000, 820, 760, 750, 740, 720.

 EXAMPLE 72. 2-Butyl-1 - [[2 '- (N-pivaloyloxymethyltetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

A mixture of 2-butyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid (0.71 g), K ₂ CO ₃ (0, 21 g) and pivalic acid iodomethyl ester (0.36 g) in dimethylformamide (2 ml) were stirred at room temperature for 17 hours. The reaction mixture was boiled in water and acidified (pH 3-4) 1 n. HCl solution. This mixture was extracted with ethyl acetate. The organic layer was washed with water, dried and evaporated to dryness, whereby a residue was obtained. This residue was purified by column chromatography on silica gel to give a colorless powder (0.2 g, 23%), melting point 188-191 ^C (decomposition).

Elemental analysis for C ₃₂ H ₃₄ N ₆ O ₄ · 0.6H ₂ O.

 Calculated, C 66.56; H, 6.14; N, 14.55.

 Found, C, 66.82; H 6.28; N, 14.13.

Spectrum 1 ^H- NMR (200 MHz, CDCl ₃ ) δ: 0.94 (3H, t); 0.96 and 1.18 (9H, s.); 1.36-1.55 (2H, m.); 1.77-1.93 (2H, m.); 2.90-2.97 (2H, m.); 5.39 (1.5H, s.); 5.81 (2H, s.); 6.36 (0.5 N. s.); 6.76-6.83 (2H, m.); 6.96-7.03 (2H, m.); 7.20-7.29 (1H, m.); 7.38-7.97 (6H, m.).

Infrared spectrum (KBr), cm ^-1 : 1760, 1600, 1460, 1410, 1275, 1240, 1125, 1100, 760.

 The following compounds (working examples 73-76) were obtained in accordance with the procedure described in working example 36.

 EXAMPLE 73. 2-Ethyl-1-pivaloyloxymethyl ester - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carbon acids.

 EXAMPLE 74. Pivaloyloxymethyl ether 2-propyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carbon acids.

 EXAMPLE 75. 1- (Cyclohexyloxycarbonyloxy) ethyl 2-propyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

 EXAMPLE 76. 1- (Cyclohexyloxycarbonyloxy) ethyl ester 2-ethyl-1 - [[2 '- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.

 EXPERIMENTAL EXAMPLE 1. Inhibition of the binding of angiotensin II to the angiotensin receptor.

 METHOD

 An experiment on the inhibition of the binding of angiotensin II (AP) to the AP receptor is carried out using a modification of the method of Douglas et al. (Endocrinology, 102, 685-696 (1978)). Receptor A-P is obtained on the membrane fraction of bovine adrenal cortex.

The compound of this invention (10 ^-6 or 10 ^-5 mol and ¹²⁵ J-A-P (1.85 kBq (50 μl) is added to the membrane fraction of the receptor and this mixture is incubated for 1 h at room temperature. Angiotensin bound to the receptor II and free ¹²⁵ J-angiotensin II are separated by a filter (Whatman fiberglass biological filter) and the radioactivity of ¹²⁵ J-angiotensin II bound to the receptor is measured.

 Results.

 The results specific for the compounds of this invention are presented in the table.

 EXPERIMENTAL PRI me R 2. The inhibitory effect of the compounds according to the invention in relation to the pressor effect of angiotensin II.

 METHOD

 The conditions of the experiment. Rats with tolerances are used (9-week-old, males). On the eve of the experiment, these animals cannulated into the femoral artery and vein under anesthesia from sodium pentobarbital. Animals are not allowed to eat, but are provided with free access to drinking water before the experiment. On the day of the experiment, an arterial catheter is connected to a blood pressure sensor and the average blood pressure is recorded using a polygraph. Prior to drug administration, a control measurement of the increase in blood pressure caused by intravenous administration of angiotensin II (100 ng / kg) is performed. Medicines are administered by mouth, and then at each measurement step, intravenous administration of angiotensin II is performed and the pressor effect is measured in a similar manner. By comparing the pressor effect before and after drug administration, the percentage value of the drug inhibition of the pressor effect caused by angiotensin II is determined.

 Results.

 The results characteristic of the compounds of the invention are shown in the table.

Claims (40)

1. Derivatives of benzimidazole of General formula I

where R ₁ is a substituted alkyl group;
R ₁ and R ₃ - independently from each other, a group capable of forming an anion, or a group that can be transformed into such a group;
ring A is a benzene ring, which, in addition to the group indicated by R ₂ , optionally includes other substituents;
X is a direct bond of the phenylene group and the phenyl group or a bond through a space group, the chain of atoms of which does not exceed two;
or its salt. 2. The compound according to claim 1, characterized in that R ₁ is a lower C ₁ - C ₈ alkyl group with a straight or branched chain, which may be substituted by a hydroxyl group, optionally substituted by an amino group, a halogen, a lower C ₁ - C ₄ an alkylthio group or a lower C ₁ -C ₄ alkoxy group. 3. The compound according to claim 2, characterized in that the substituted amino group represents an amino group, an N-lower C ₁ -C ₄ alkylamino group or an N, N-lower C ₁ -C ₄ dialkylamino group. 4. The compound according to claim 1, characterized in that R ₁ is a lower C ₂ - C ₅ alkyl group which may be substituted by a hydroxyl group, an amino group, a halogen or a lower C ₁ - C ₄ alkoxy group. 5. The compound according to claim 1, characterized in that R ₂ is a group of the formula
- (CH ₂ ) _n CO-D,
where D is hydrogen, hydroxyl group, substituted amino group, halogen or, if necessary, alkoxyl group;
n is an integer from 0 to 1,
a cyano group, substituted tetrazolyl, phosphoric acid, sulfoxylate, phenolic hydroxyl group, substituted alkoxy group, trifluoromethanesulfonic acid amide or lower C ₁ -C ₃ -alkyl group, which may be substituted by a hydroxyl group or, optionally, substituted by an amino group. 6. The compound according to claim 5, characterized in that the substituted amino group indicated by D or a substituent of a lower C ₁ -C ₃ alkyl group represents an amino group, an N-lower C ₁ -C ₄ alkylamino group or an N, N-lower C ₁ - C ₄ dialkylamino group. 7. The compound according to p. 5, characterized in that the substituted alkoxy group, denoted by the symbol R ₂ or D, represents a lower C ₁ - C ₆ alkoxy group, the alkyl part of which may be substituted by a hydroxyl group, an amino group, an N-lower C ₁ - C ₄ -alkylamino, N, N-lower C ₁ - C ₄ -alkylamino, halogen, lower C ₂ - C ₆ alkanoyloxy, lower C ₁ - C ₆ alkoxy, lower C ₁ - C ₆ -alkylthio or lower C ₁ - C ₆ alkoxycarbonyloxy group.  8. The compound according to claim 5, characterized in that, if necessary, the protected tetrazolyl is tetrazolyl, which can be protected by alkyl or acyl. 9. The compound of claim 8, wherein the acyl is lower C ₂ - C ₅ alkanoyl or benzoyl. 10. The compound of claim 8, wherein the alkyl is lower C ₁ -C ₄ -alkyl. 11. The compound according to claim 1, characterized in that R ₂ is a group of the formula
- (CH ₂ ) _n - CO-D,
where D is hydrogen, hydroxyl group, amino group, N-lower C ₁ - C ₄ alkylamino group, N, N-lower C ₁ - C ₄ dialkylamino group or lower C ₁ - C ₆ alkoxy group, the alkyl part of which may be substituted a hydroxyl group, an amino group, a halogen, a lower C ₂ - C ₆ alkanoyloxy group, a lower C ₁ - C ₆ alkoxy group, a lower C ₁ - C ₆ alkylthio group or a lower C ₁ - C ₆ alkoxycarbonyloxy group,
n represents an integer from 0 to 1,
or tetrazolyl, which may be protected with lower C ₁ -C ₄ alkyl, lower C ₁ -C ₅ alkanoyl or benzoyl. 12. The compound according to claim 1, characterized in that R ₂ is a group of the formula
-CO-D ′,
where D ′ is a hydroxyl group, an amino group, an N-lower C ₁ –C ₄ alkylamino group, N, an N-lower C ₁ –C ₄ dialkylamino group or a lower C ₁ –C ₆ alkoxyl group, the alkyl part of which may be substituted with a hydroxyl a group, an amino group, a halogen, a lower C ₂ -C ₆ alkanoyloxy group, a lower C ₁ -C ₆ alkoxy group, a lower C ₁ -C ₆ alkylthio group or a lower C ₁ -C ₆ alkoxycarbonyloxy group, or tetrazolyl, which may be protected lower C ₁ -C ₄ -alkyl; lower C ₅ -C ₅ -alkanoyl or benzoyl. 13. The compound according to p. 12, characterized in that D ′ is a hydroxyl group, an amino group, an N-lower C ₁ -C ₄ alkylamino group, N, an N-lower C ₁ - C ₄ dialkylamino group or a lower C ₁ - C ₄ -alkoxyl group, the alkyl part of which may be substituted by a hydroxyl group, an amino group, a halogen or a lower C ₁ -C ₄ alkoxy group. 14. The compound according to claim 1, wherein R ₃ is carboxyl, tetrazolyl, trifluoromethanesulfonic acid amide, phosphoric acid, sulfonic acid, cyano or lower C ₁ -C ₄ alkoxycarbonyl, each of which may be protected by alkyl or acyl. 15. The compound according to 14, characterized in that the alkyl is lower C ₁ -C ₄ -alkyl. 16. The compound according to 14, characterized in that the acyl is lower C ₂ - C ₅ alkanoyl or benzoyl. 17. The compound according to claim 1, characterized in that R ₃ is carboxyl or tetrazolyl. 18. The compound according to claim 1, characterized in that ring A represents a benzene ring comprising substituents other than the group designated by R ₂ , said substituents selected from halogen, nitro group, cyano group, optionally substituted amino group and group of formula
YR,
where Y is a bonding group of atoms, -0-, -S, or

R is hydrogen, a substituted lower alkyl group or a group of the formula
-CO-D ′ ′,
where D ″ is hydrogen, a substituted alkoxyl group, a substituted amino group, a halogen or a hydroxyl group. 19. The compound according to p. 18, characterized in that, if necessary, the substituted amino group represents an amino group, an N-lower C ₁ -C ₄ alkylamino group, N, an N-lower C ₁ - C ₄ dialkylamino group, an N-arylamino group or an alicyclic amino group. 20. The compound according to p. 18, characterized in that, if necessary, the substituted lower alkyl group represents a lower C ₁ - C ₄ -alkyl group, which may be substituted by a hydroxyl group, an amino group, an N-lower C ₁ - C ₄ -alkylamino group , N, N-lower C ₁ - C ₄ dialkylamino group, N-arylamino group, alicyclic amino group, halogen or lower C ₁ - C ₄ alkoxy group. 21. The compound according to p. 18, characterized in that, if necessary, the substituted alkoxyl group represents a lower C ₁ -C ₄ alkoxy group, which may be substituted by a hydroxyl group, an amino group, an N-lower C ₁ -C ₄ alkylamino group, N, N-lower C ₁ - C ₄ dialkylamino group, N-arylamino group, alicyclic amino group, halogen or lower C ₁ - C ₄ alkoxy group.  22. Connection PP. 19 to 21, characterized in that the alicyclic amino group is morpholino, piperidino or N-phenylpiperazino.  23. The compound according to claims 19 to 21, characterized in that the N-arylamino group is a phenylamino group. 24. The compound according to p. 18, characterized in that the substituents are selected from a class of elements including halogen, lower C ₁ -C ₄ -alkyl, lower C ₁ -C ₄ -alkoxyl group, nitro group, group of the formula
-CO-D ′ ′,
where D ′ ′ is a hydroxyl group or lower C ₁ - C ₂ -alkyl,
and an amino group which may be substituted with lower C ₁ -C ₄ alkyl. 25. The compound according to p. 18, wherein the substituents are selected from the class of elements, including halogen and lower C ₁ -C ₄ -alkyl. 26. The compound according to p. 18, wherein the substituents represent a group of the formula
YR,
where Y is a bonding group of atoms;
R is hydrogen. 27. The compound according to claim 1, characterized in that the spatial group, the chain of atoms of which does not exceed two, is a diatomic chain selected from the group consisting of lower C ₁ -C ₄ alkylene,

28. The compound according to claim 1, characterized in that X is a direct bond of phenylin and phenyl. 29. The compound according to claim 1, characterized in that it is a compound of the formula

where R ₁ is lower C ₂ -C ₅ alkyl, which may be substituted by hydroxyl, amino, halogen or lower C ₁ -C ₄ alkoxy group;
R ₂ is a group of the formula
-CO-D ′,
where D ′ is hydroxyl, amino group, N-lower C ₁ - C ₄ -alkylamino group, N, N-lower C ₁ - C ₄ -alkylamino group or lower C ₁ - C ₄ -alkoxyl group, which may be substituted by hydroxyl, amino group, halogen or a lower C ₁ -C ₄ alkoxy group, or tetrazolyl, which may be protected by lower C ₁ -C ₄ alkyl, lower C ₂ -C ₅ alkanoyl or benzoyl, is carboxyl or tetrazolyl, which may be protected by lower C ₁ —C ₄ alkyl, lower C ₂ —C ₅ alkanoyl or benzoyl;
R ₃ is hydrogen, halogen, lower C ₁ -C ₄ alkyl, lower C ₁ is C ₄ alkoxy group, nitro group, a group of the formula
-CO-D ′ ′,
where D ″ is hydroxyl or lower C ₁ - C ₂ alkoxy group or amino group which may be substituted with lower C ₁ - C ₄ alkyl. 30. The compound according to clause 29, wherein R ₁ is hydrogen, lower C ₁ is C ₄ alkyl or halogen. 31. The compound according to clause 29, wherein R ₁ is hydrogen. 32. The compound according to clause 29, wherein R ₂ is a group of the formula
-CO-D ′,
where D ′ is hydroxyl, amino group, N-lower C ₁ - C ₄ -alkylamino group, N, N-lower C ₁ - C ₄ -alkylamino group or lower C ₁ - C ₄ -alkoxyl group which may be substituted by hydroxyl, amino group, halogen or lower C ₁ - C ₄ alkoxy group. 33. The compound according to claim 1, characterized in that R ₃ is tetrazolyl.  34. The compound according to claim 1, characterized in that its salt is a pharmaceutically acceptable salt.  35. The compound according to claim 1, characterized in that it is 2-butyl-1 - [[2′- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid.  36. The compound according to claim 1, characterized in that it is 2-butyl-1 - [[2′- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid pivaloyloxymethyl ester .  37. The compound according to p. 1, characterized in that it is 1- (cyclohexyloxycarbonyloxy) ethyl ester 2-butyl-1 - [[2′- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole -7-carboxylic acid.  38. The compound according to claim 1, characterized in that it is 2-butyl-1 - [[2′- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid methyl ester .  39. The compound according to p. 1, characterized in that it is 2-propyl-1 - [[2′- (1H-tetrazol-5-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid. 40. A method of obtaining derivatives of benzimidazole, characterized in that the compound of General formula II

where each character has the specified values,
reacted with a compound of the general formula
R is Y,
where R ₁ has the indicated meanings;
Y is a carboxyl, aldehyde, iminoether, iminothioether, amidine or cyano group,
and, if necessary, if in the obtained compound R ₃ represents a cyano group, it is converted by means of azidation to tetrazolyl, or if R ₃ in the obtained compound of formula I is an ester group, this group is converted to a carboxyl group by hydrolysis, or if R ₃ and / or R ₂ in a compound of formula I is carboxyl, said group is converted to an ester group by esterification.  41. A pharmaceutical composition that is antagonistic to angiotensin II, containing an active substance that is a benzimidazole derivative and a pharmaceutically acceptable carrier, excipient or diluent, characterized in that a compound of formula II (according to claim 1) or a salt thereof is used as a benzimidazole derivative in an effective amount.

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