JP2001519806A - Compounds and compositions for treating diseases associated with serine protease activity, especially tryptase activity - Google Patents

Abstract

(57) Abstract Novel compounds, compositions and methods are described that are effective for the prevention and treatment of mast cell-mediated inflammatory diseases. A preferred aspect of the present invention is a compound represented by formula (II): Wherein the dotted lines independently represent optional bonds; each R ² is independently (C _1-6 ) alkyl, (C _1-6 ) alkyloxy, halo, or hydroxy; R ³ is independently (C _1-5 ) alkyl, (C _1-6 ) alkyloxy, halo or hydroxy; X ³ is —C (O) — or —CR ⁷ R ⁸ —; X ⁸ is —CH (R ¹ ) _n2 — or —C (R ¹ ) _n1 =, wherein R ¹ is amino (N _1-4 ) azolidinyl, amino (N _1-4 ) azolyl, (N _{1- 4)} azolidinyl, (N _1-4) ^{azolyl, -NHC (NH) NR 9 R} 9, -C (NR 9) R 9, -C (NH) NHR 9, -C (NH) NR 10 R 10 or - (CR ¹¹ R ¹¹ ) _y NH ₂ , or X ⁸ is -N = or -NH (R ¹ ) _n3- , wherein R ¹ is -C (NR ⁹ ) R ⁹ , -C (NH) an NHR ¹⁰ or ^{-C (NH) NR 10 R 10} , wherein each R ⁹ is independently hydrogen or (C _1-6) alkyl, and the individual R ¹⁰ Germany To be a (C _1-6) alkyl; and X ⁹ is -CH (R ⁴⁾ - or -C (R ⁴⁾ a =, wherein R ⁴ is -R ^12, -OR ^12, -N ( R ¹³ ) R ¹² , -SR ¹² , -S (O) R ¹² , -S (O) ₂ R ¹² , -S (O) ₂ OR ¹² , -S (O) ₂ N (R ¹³ ) R ¹² , −N (R ¹³ ) S (O) ₂ R ¹² , −C (O) R ¹² , −C (O) OR ¹² , −C (O) N (R ¹³ ) R ¹² , −N (R ¹³ ) C ^{(O) R 12, -OC (} O) N (R 13) R 12, -N (R 13) C (O) OR 12, - (CH 2) n4 N (R 13) C (O) N (R ^{13) R 12, -OP (O} ) (oR 13) oR 12 or ^{-C (O) N (R 14} ) CH (COOH) is R ^12, or X ⁹ is -N = or -N (R ⁴⁾ Where R ⁴ is -C (O) R ¹² , -C (O) OR ¹² , -C (O) N (R ¹³ ) R ¹² , -OC (O) N (R ¹³ ) R ¹² Or —C (O) N (R ¹⁴ ) CH (COOH) R ¹² , wherein R ¹² , R ¹³ and R ¹⁴ are as defined in the Summary of the Invention; R ⁵ is hydrogen, or (C _1-4) alkyl, R ⁶ is hydrogen or (C _1-4) alkyl, wherein said alkyl is optionally, (C _1-4) alkyloxy, hydro Substituted by one to two substituents independently selected from shea and sulfo, R ⁷ is hydrogen or methyl, and R ⁸ is hydrogen, methyl or hydroxy] The compounds, compositions and methods Inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis, and other types of immune-mediated inflammatory diseases, such as rheumatoid arthritis, conjunctivitis and inflammatory bowel disease, various skin physiological conditions, and It is effective for the prevention and treatment of certain viral conditions. The compound comprises a potent and selective inhibitor of mast cell protease tryptase. Compositions for treating these conditions include oral, inhalational and parenteral preparations, and devices comprising such preparations.

Description

DETAILED DESCRIPTION OF THE INVENTION To treat diseases associated with serine protease activity, especially tryptase activity Compounds and compositions Field of the Invention:   This application is an application filed on December 14, 1994, which is incorporated herein by reference. Application No. filed on April 7, 1997, which is a continuation-in-part of application number 08 / 357,491 No. 08 / 833,674 which is a continuation-in-part application of Ser. Compounds and compositions for treating diseases associated with leptase activity. Field Description:   Tryptase, a potent protease secreted from human mast cells, It appears to be involved in neuropeptide processing and tissue inflammation. Tripta For several hours after anaphylaxis, serum concentrations rise in the bloodstream (Schwartz et al. (1). 987) N. Eng. J. Med. 316: 1622-1626), from atopic patients after a specific antigenic attack In the nasal and lung lavage fluids (Castells et al. (1988) J. Allerg. Clin. Immunol). . 141: 563-568), and after an internal bronchial allergen attack, Elevates in lung lavage fluid. Smokers often tryptonase in bronchoalveolar lavage fluid With a significant increase in levels, this finding suggests that protein from activated mast cells Some hypotheses about the release of Nase contributes to lung destruction in emphysema in smokers (Celenteron et al. (1988) Chest 94: 119-123). In addition, birds Putase has been shown to be a potent mitogen for fibroblasts, This is related to pulmonary fibrosis and interstitial lung disease. (Ross et al. (1991) J. Clin. Invest. 88: 493-499).   Asthma is recognized as an inflammatory disease (Hood et al. (1984) Benjamin-Cummings, e d. Immunology 2nd ed.), And sometimes immunospecific allergens and Due to the progressive development of hyperresponsiveness of the trachea and bronchi to chemical or physical stimuli. It is characterized. The disease has multiple occurrences in both the acute and chronic stages. Biological mediators. The hyperresponsiveness of asthmatic bronchioles can Stimulates and damages the overlying epithelium and causes pathological thickening of the underlying tissue It appears to be the result of an accelerated chronic inflammatory response. For patients with only mild asthma Bronchial biopsies have inflammation characteristics in the airway walls.   An allergic response to an inhaled allergen can initiate an inflammatory chain. Can be. For example, an allergen can bind IgE located on the cell surface. Mast cells and basophils present in the epithelium and the underlying smooth muscle tissue by Can be activated. Activated mast cells pre-form many of the inflammatory responses Release an activated or primary chemical mediator (eg, histamine), and Many other secondary mediators of inflammation (eg, superoxide, lipid-derived Mediators, etc.) on the fly. In addition, some large molecules ( For example, proteoglycans, tryptase, chymase, etc.) Released by vesicle degranulation.   The release of those preformed mediators from mast cells is probably empty Early bronchial stenosis in asthmatic response to qi-carried allergens Is the cause. The initial phase of the asthmatic response occurs approximately 15 minutes after exposure to the allergen. And general Followed by a recovery phase for 1-2 hours. 25-35% of the patient population A further decline in respiratory function is experienced, which peaks after 6 to 12 hours of exposure. This The late reaction phase involves inflammatory cells (eg, eosinophils, neutrophils, Lymphocytes, etc.). These infiltrating cells are derived from mast cells Attacked by the release of the chemotactic agent, and It is then activated during the late reaction phase. This late asthmatic response is triggered by granulocyte secretion. It appears to be a secondary inflammatory response mediated in part by the activity.   Tryptase is used to degrade vasodilator and bronchorelaxant neuropeptides (Caughey et al. (1988) J. Pharmacol. Exp. Ther. 244: 133-137; Francois et al. (1988) J. Phar macol. Exp. Ther. 248: 947-951; and Tam et al. (1990) Am. J. Respir. Cell M ol. Biol. 3: 27-32), and regulation of bronchial responsiveness to histamine (Sekizawa Such. (1989) J.C. Clin. Invest. 83: 175-179). Those discoveries Tryptase destroys bronchodilator peptides, resulting in airflow in asthma. It suggests that bronchial stenosis can be enhanced. Tryptase, fibrino Decomposes α-chain and high molecular weight kininogen, It suggests that the enzyme plays a role with heparin as a local anticoagulant. G Leptase is prostromelysin (pro-MMP-3) and procollagen through MMP-3. Activates the protease (pro-MMP-1), which indicates that tryptase is Implications for remodeling and joint destruction in rheumatoid arthritis . In addition, administration of tryptase inhibitors can be used in allergen-challenged sheep. (Clark et al. (1995) Am. J. Res. pir. Crit. CareMed. 152: 2076-2083), and allergies Inhibit immediate skin response to intradermal injection of allergens in male sheep (Mol inari etc. (1995) Amer. Physiol. Soc. 79 (6); 1966-1970). All of the above discoveries Is a therapeutic agent for treating asthma and other diseases associated with inflammation of the respiratory tract. The applicability of all tryptase inhibitors is clearly shown.   These and other documents referred to throughout this invention, such as patents and patents The disclosure of the application is incorporated herein by reference. Summary of the Invention   The present application provides a compound of formula I: Wherein n1 is o or 1;   n2 is 0, 1, 2, 3, or 4;   n3 is 0, 1, 2, 3, or 4;   A is taken together with B to form a fused heterobicyclic group containing from 8 to 12 ring atoms. Wherein each ring comprises from 5 to 7 ring members, wherein each ring atom is a heteroatom And X¹And X^TwoIs an adjacent ring member of an aromatic ring;¹Is- N =, -NR^Five-, -O-, and -S-, a heteroatom component selected from the group consisting of Where R^FiveIs hydrogen, (C_1-6) Alkyl or hetero (C_2-6) Is alkyl;   C is a fused heteropolycyclic group containing 8 to 18 ring atoms and any of its carbocycles Make up the formula ketone, thioketone and imino ketone derivatives, wherein each ring is from 5 to 5 Containing 7 ring members, each ring atom can be a heteroatom, X^FourAnd X^FiveIs Adjacent ring members of an aromatic ring And X^FiveIs -N-, -NR⁶-, A heteroatom selected from -O- and -S- Minutes, where R⁶Is hydrogen, (C_1-8) Alkyl or hetero (C_2-12) Alkyl A group selected from the group consisting of (C_1-6) Alkanoyloxy, (C_1-6) Archi Luamino, di (C_1-6) Alkylamino, tri (C_1-6) Alkyl ammonium, ( C_1-6) Alkylcarbamoyl, di (C_1-6) Alkylcarbamoyl, (C_1-6) Alkyloxy, (C_1-6) Alkyloxycarbonyl, (C_1-6) Alkyl oxy Disulfonyl, amino, carboxy, carbamoyl, (C_6-14) Aryl, halo , Hetero (C_5-141.) 1 independently selected from aryl, hydroxy and sulfo Or may be substituted by two substituents) or as defined below R;   X^ThreeIs -O-, -S-, -S (O)-, -S (O)_Two−, −C (O) −, −NR⁷-Or -CR⁷R⁸ -Where R⁷Is hydrogen, (C_1-6) Alkyl or hetero (C_2-12) Al Kill or R⁶Together with (C_2-4) Alkylene or hetero (C_{2- Four} A) forming an alkylene;⁸Is hydrogen, (C_1-6) Alkyl or hydro Is xy or R⁷Together with (C_2-6) Alkylene or (C_1-6A) Alkylidene, where R⁷And / or R⁸Any of the aliphatic or The alicyclic component is (C_1-6) Alkylamino, di (C_1-6) Alkylamino, tri ( C_1-6) Alkyl ammonium, (C_1-6) Alkyloxy, (C_1-6) Alkylo Xycarbonyl, (C_1-6) Alkanoyloxy, amino, carboxy, carb Moyle, (C_1-6) Alkylcarbamoyl, di (C_1-6) Alkylcarbamoyl, Optionally substituted by one or three substituents selected from halo and hydroxy May be   R₁Is amino (N_1-4) Azolidinyl, amino (N_1-4) Azori Le, (N_1-4) Azolidinyl, (N_1-4) Azolyl, carbamoyl, cyano,-(C H_Two)_xNHC (NR⁹) R⁹, − (CH_Two)_xNHC (NH) NR⁹R⁹−, −C (NR⁹) R⁹, −C (NH) NHR^Ten, −C (NH ) NR^TenR^TenOr-(CR¹¹R¹¹)_yNH_TwoAnd the available valences that make up B Attached to any ring atom having x is 0 or 1 and y is 0, 1, 2 or 3, each R⁹Is independently hydrogen or (C_1-6) Alkyl Each R^TenAre independently (C_1-6) Is alkyl and each R¹¹Is independently water Elementary or (C_1-3) Is alkyl or another R¹¹And both are connected Together with the carbon atom to form cyclopropyl, where R¹Make up aliphatic Or the alicyclic component is optionally (C_1-6) Alkyloxycarbonyl, (C_1-6) Al Canoyloxy, carboxy, carbamoyl, (C_1-6) Alkyl carbamoyl , Di (C_1-6) Alkylcarbamoyl, (C_1-6) Alkylsulfonyl and hydro Optionally substituted by one or two substituents independently selected from xy;   Individual R^TwoAre independently (C_1-6) Alkyl, (C_1-6) Alkyloxycarbo Nil, (C_1-6) Alkanoyloxy, (C_1-6) Alkyloxy, carboxy, Carbamoyl, (C_1-6) Alkylcarbamoyl, di (C_1-6) Alkyl carbamo Il, (C_1-6) Alkylsulfinyl, (C_1-6) Alkylsulfonyl, (C_{1- 6} A) alkylthio, halo or hydroxy, and available to constitute B Attached to any valence ring atom, wherein R^TwoConstituents of aliphatic components Is optionally (C_1-6) Alkyloxycarbonyl, (C_1-6) Alkanoyloxy , Carboxy, carbamoyl, (C_1-6) Alkylcarbamoyl, di (C_1-6A) Lucilcarbamoyl, (C_1-6) Independent from alkylsulfonyl and hydroxy Optionally substituted by one or two substituents selected;   Individual R^ThreeAre independently (C_1-6) Alkyl, (C_1-6) Alkyloxy, (C_{1 -6} ) Alkylthio, cyano, halo, perhalo (C_1-6) Alkyl or hydroxy And is attached to any ring atom having an available valence constituting C Done; and   R^FourIs -R¹², −OR¹², −N (R¹³) R¹², −SR¹², −S (O) R¹², −S (O)_TwoR¹², −S (O )_TwoOR¹², −S (O)_TwoN (R¹³) R¹², −N (R¹³) S (O)_TwoR¹², −C (O) R¹², −C (O) OR¹², −C (O ) N (R¹³) R¹², −N (R¹³) C (O) R¹², −OC (O) N (R¹³) R¹², −N (R¹³) C (O) OR¹², − (CH_Two)_Z N (R¹³) C (O) N (R¹³) R¹², −OP (O) (OR¹³) OR¹²Or -C (O) N (R¹⁴) CH (COOH) R¹²Is And any of the available valence ring atoms constituting C; here   z is 0, 1 or 2;   R¹²Is -R^FifteenOr -X⁶− (R^Fifteen)_n15Where n15 is 1 or 2, X⁶Is (C_1-10) Alkylene, cyclo (C_3-10) Alkylene, hetero (C_2-10) Alkylene or heterocyclo (C_3-10A) alkylene and the individual R^FifteenIs Independently, hydrogen (C_6-14) Aryl, cyclo (C_3-14) Alkyl, polycyclo ( C_6-14) Aryl, heteropolycyclo (C_6-14) Aryl, heterocyclo (C_{3- 14} ) Alkyl, hetero (C_5-14A) aryl or as defined below;   R¹³Is hydrogen, (C_1-6) Alkyl or hetero (C_2-6) Is alkyl;   R¹⁴Is hydrogen or (C_1-6) Is alkyl or X⁶And R^FifteenTogether with T (C_3-4) Forming an alkylene;   R^FourAny of the aliphatic and cycloaliphatic components that make up_1-6) Alkyl, (C_1-6 ) Alkylamino, di (C_1-6) Alkylamino, (C_1-6) Alkyl carba Moyle, di (C_1-6) Alkyl cal Bamoyl, (C_1-6) Alkyloxy, (C_1-6) Alkyloxycarbonyl, ( C_1-6) Alkylsulfinyl, (C_1-6) Alkylsulfonyl, (C_1-6) Al Kirthio, amino, (C_6-10) Arylsulfonyl, carbamoyl, carboxy Independent from Cyano, Guanidino, Halo, Hydroxy, Mercapto, and Uried Optionally substituted with 1 to 5 substituents selected as such;   R^FifteenIs any of the aromatic components cyano, guanidino, halo, halo- Replaced (C_1-8) Alkyl, -R¹⁶, −OR¹⁶, −SR¹⁶, −S (O) R¹⁶, −S (O)_TwoR¹⁶ , −S (O)_TwoN (R¹³) R¹⁶, −C (O) R¹⁶, −C (O) OR¹⁶And -C (O) N (R^Fifteen) R¹⁶Independent from May optionally be substituted by one to three substituents selected by^Fifteen Is as defined above, and R¹⁶Is hydrogen, optionally monosubstituted Good (C_1-8) Alkyl wherein the optional substituent is (C_1-6) Alkylamino, di (C_1-6) Alkylamino, tri (C_1-6) Alkyl ammonium, (C_1-6) Al Kircarbamoyl, di (C_1-6) Alkylcarbamoyl, (C_1-6) Alkyl oxy Cycarbonyl, (C_1-6) Alkyloxysulfonyl, amino, carboxy, ka Rubamoyl, hydroxy or sulfo), cyclo (C_3-6) Alkyl, f Terrorism (C_1-8) Alkyl, hetero (C_3-6) Aryl, heterocyclo (C_3-6A) Alkyl or phenyl;   Provided that n2 is 0 or R^TwoIs (C_1-6) Alkyl or (C_1-6) Alkyl Oxy, n3 is 0, or^ThreeIs (C_1-6) Alkyl or (C_1-6A) Is alkyloxy and R^FourIs hydrogen, (C_1-10) Alkyl or (C_1-10A) In the case of alkyloxy, n1 is not 0. A compound represented by the formula: -Oxide derivatives, prodrug derivatives, protected derivatives, individual isomers, And mixtures thereof, and pharmaceutically acceptable salts.   The present invention also provides pharmaceutical compositions of the compounds of the present invention. Their pharmaceutical compositions Are available in a variety of forms, including oral administration forms, inhalation forms, and injectable and infusible solutions. Can exist. When used in inhalation or aerosol form, The compound can be converted to an aerosol form, a pharmaceutically acceptable carrier solution or Used in combination with dry powder. Similarly, when administered orally, the compounds of the invention Is combined with a pharmaceutically acceptable carrier suitable for such oral administration. Used. The present invention when used for the treatment of immune-mediated inflammatory skin conditions Are used in combination with a non-toxic pharmaceutically acceptable topical carrier. You. The compounds of the present invention may be used as anti-inflammatory agents or other asthma treatments, such as β-adrenaline. Phosphorus agonists, anti-inflammatory corticosteroids, anticholinergics, bronchodilation Agents such as methylxanthene and the like can be used in combination.   The compounds described herein are useful in immune-mediated inflammatory diseases, and especially in the respiratory tract For example, asthma, and especially hyperresponse associated with chronic asthma and allergic rhinitis. Useful for prevention and treatment of diseases associated with the responsive phase. Therefore, the present invention Also provided is a method of treating an immune-mediated inflammatory disease, wherein the method has an immune-mediated inflammatory disease. The patient is administered a therapeutically effective dose or amount of a compound of the present invention. Further, the present specification Compounds described herein are useful for treating syncytial virus infection . BRIEF DESCRIPTION OF THE FIGURES   FIG. 1 shows controls (open squares) versus time (hours) versus 2- (5-aminomethyl). -1H-benzimidazol-2-ylmethyl) -N- (3-phenylpropyl ) -1H-Benzimidazole-5-ca The specific lung tolerance of ruboxamide (compound 4; filled squares) is compared.   FIG. 2 was treated with compound 4 by three 1 mg dose aerosol doses. Airway hyperresponsiveness of sheep treated with antigen versus challenged sheep (as PC400 (Measured). Detailed description of the invention Definition:   Unless otherwise noted, the following terms used in the specification and claims It is defined for the purposes of the invention and has the meaning indicated below:   “Alkanoyl” refers to the group —C (O) R where R is all of the indicated carbon atoms. Alkyl as defined below (eg, (C_1-6A) Lucanoyl has the formyl, acetyl, propionyl, butyryl, isobutyryl, Crotonyl, isocrotonyl, and the like).   "Alicyclic component" means any saturated or unsaturated, monocyclic or polycyclic hydrocarbon of a group. Means a prime part. For example, a cycloaliphatic component may be as defined herein. Cycloalkyl, and cycloalkylalkyl, cycloalkyloxy, cycloalkyl Loalkylcarbonyl, cycloalkylalkanoyl, cycloalkylcarbamo And cycloaliphatic moieties comprising the like.   “Aliphatic component” means any straight or branched chain, saturated or unsaturated carbonized Means the hydrogen moiety. For example, the aliphatic component may be as defined herein. Alkyl or heteroalkyl, and alkyloxy, arylalkyl, f Teloarylalkyl, alkylcarbamoyl, alkanoyl, arylalk Noil, Hete An aliphatic moiety comprising loarylalkanoyl and the like is meant.   “Alkyl” for the purposes of the present invention means straight chain or having the indicated number of carbon atoms. A branched chain, a saturated or unsaturated aliphatic hydrocarbon group, and its ketone, thioketone or Means imino ketone (eg, (C_1-8) Alkyl is methyl, ethyl, Propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, Nil, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl , 3-butenyl, 2-methylallyl, ethynyl, 1-propynyl, 2-propynyl , 3-oxopentyl, 1-thioxopentyl, 3-iminopentyl, etc. Including).   “Alkylene” means a saturated or unsaturated divalent carbon having the number of carbon atoms indicated. Hydride group and any of its ketones, thioketones, imino ketones and substituted A derivative (eg, (C_1-10) Alkylene is methylene (-CH_Two−) , Ethylene (-CH_TwoCH_Two−), Methyl ethylene, vinylene, ethinylene, trimethyl Ren (-CH_TwoCH_TwoCH_Two-), 2-oxotrimethylene (-CH_TwoC (O) CH_Two−), 2-H Atrimethylene (-CH_TwoC (S) CH_Two-), 2-iminotrimethylene (-CH_TwoC (NH) CH_Two -), Propylene (-CH_TwoCH = CH- or CH = CHCH_Two−), Propanilidene (= CHCH_Two CH_Two-), Propendylene (= CHCH = CH-), 1-aminotetramethylene, pen Tamethylene, etc.).   "Alkylidene" means the radical = CRR, wherein each R is independently Or an alkyl as defined above having the indicated number of carbon atoms (e.g. For example, (C_1-6) Alkylidene is methylidene, ethylidene, propylidene, Isopropylidene, and the like).   "Alkyloxy" refers to the group -OR where R is the number of carbon atoms indicated. Is an alkyl as defined above (eg, (C_1-6) Archi Luoxy has the groups methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, tert-butoxy, vinyloxy, allyloxy , 1-propenyloxy, isopropenyloxy, 1-butenyloxy, 2-butane Tenenyloxy, 3-butenyloxy, 2-methylallyloxy, ethynyloxy , 1-propynyloxy, 2-propynyloxy, and the like).   “Alkylsulfinyl”, “alkylsulfonyl”, and “alkylthio” Are the groups -SOR, -S (O)_TwoR and -SR, where R is the indicated carbon Alkyl as defined above having a number of atoms (eg (C_1-6 ) Alkylsulfonyl is methylsulfonyl, ethylsulfonyl, propylsulfonyl Honyl, isopropylsulfonyl, butylsulfonyl, sec-butylsulfonyl , Isobutylsulfonyl, tert-butylsulfonyl, vinylsulfonyl, allyl Sulfonyl, 1-propentylsulfonyl, isopropentylsulfonyl, 1- Butenylsulfonyl, 2-butenylsulfonyl, 3-butenylsulfonyl, 2- Methylallylsulfonyl, ethynylsulfonyl, 1-propynylsulfonyl, 2 -Propynylsulfonyl, and the like).   “Ammonio” refers to the group —NH_Three ⁺Means   “Amidino” refers to the group —C (NH) NH_TwoMeans   “Amino” refers to the group —NH_TwoMeans   An “animal” is a human, non-human mammal (eg, dog, cat, rabbit, cow, Including horses, sheep, goats, pigs, deer, etc.) and non-mammals (eg, birds, etc.) .   “Aryl” is an aromatic monocyclic or fused multiple ring containing the indicated number of carbon atoms. Means a cyclic hydrocarbon group, wherein each ring contained therein is composed of six ring members (For example, (C_6-14) Aryl is phenyl, naphthyl, anthracene Phenanthrenyl, etc.).   “Arylsulfonyl” refers to a radical —S (O)_TwoMeans R, where R is the indicated carbon source An aryl as defined above having a number of children (eg, (C_6-10 ) Arylsulfonyl includes phenylsulfonyl, naphth-1-ylsulfonyl, Etc.).   "Aromatic component" means any aromatic portion of a group. For example, fragrance Group members include aryl and heteroaryl as defined herein, And arylalkyl, heteroarylalkyl, polycycloaryl, An aromatic moiety comprising ropolycycloaryl and the like is meant.   “Azolidinyl” is a saturated or unsaturated 5-membered number containing the indicated number of nitrogen atoms. Means a monocyclic group. For example, (N_1-4) Azolidinyl is pyrazolidinyl, pyro Lysinyl, imidazolidinyl, trizolidinyl, tetrazolidinyl, dihydropi Loryl, dihydroimidazolyl, dihydropyrazolyl and dihydrotriazolyl Is included.   “Azolyl” means an aromatic 5-membered monocyclic group containing the number of nitrogen atoms indicated. You. For example, (N_1-4) Azolyl is pyrrolyl, imidazolyl, pyrazolyl, Includes triazolyl and tetrazolyl.   “Carbamoyl” refers to the group —C (O) NH_TwoMeans   "Carboxy" refers to the group -C (O) OH.   “Cyano” refers to the group —CN.   “Cycloalkyl” is a saturated or saturated, including the number of carbon atoms indicated. Is an unsaturated, monocyclic or fused polycyclic hydrocarbon radical wherein the individual The ring consists of 3 to 8 ring members), and any of its carbocyclic ketones, thioke Ton and imino ketone derivatives (for example, (C_3-14) Cycloalkyl Is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclo Hexenyl, 2,5-cyclohexadienyl, bicyclo [2.2.2] octyl , Oxocyclohexyl, dioxocyclohexyl, thiocyclohexyl, etc. Include).   "Cycloalkylene" means saturated or unsaturated, including the indicated number of carbon atoms, A monocyclic or fused polycyclic hydrocarbon divalent radical wherein each ring is from 3 to 8 ring members And its carbocyclic ketone, thioketone or imino ketone derivatives (For example, (C_3-10) Cycloalkylene is 1,2-cyclopentylene, 1,1 4-cyclopentylene, 1,4-cyclohexylene, 3-cyclohexene-1, 2-ylene, 2,5-cyclohexadiene-1,4-ylene, 1,4-bicyclo [2.2.2] octylene, 5-oxo-1,3-cyclohexylene, 2,5- Dioxo-1,4-cyclohexylene, 5-thioxo-1,4-cyclohexyl And the like. )   “Deprotection” refers to the removal of any protecting groups present after a selective reaction has been performed. Mention removal.   “Disease” specifically includes any unhealthy condition of an animal or any part thereof, and Medical or veterinary therapy applied to animals, or conditions associated therewith, i.e. And unhealthy conditions that can be caused by "side effects" of therapies such as   “Fused heteropolycyclic group” includes “fused heterobicyclic group” and Means a heterocyclic group containing two to three fused rings having the number of ring members indicated; Where at least two ring members of one ring are Common to the second ring (e.g., a heteropolycyclic group containing from 8 to 18 ring atoms and Carbocyclic ketone and thioketone derivatives are 1H-benzimidazol-2-yl 1H-naphtho [2,3-d] imidazol-2-yl, 1H-imidazo [4 5-f] quinolin-2-yl, 1H-imidazo [4,5-b] pyridin-2-i 1H-phenanthro [9,10-d] imidazol-2-yl, 1H-imida Zo [4,5-g] quinoxalin-2-yl, 2,6-dioxo-2,3,6,7 -Tetrahydro-1H-purin-8-yl, 2,6-dithioxo-2,3,6 9-tetrahydro-1H-purin-8-yl, 7H-purin-8-yl, 1,6 -Dihydrocyclopentimidazol-2-yl, 4-quinolin-2-yl, and the like ).   “Guanidino” refers to the group —NHC (NH) NH_TwoMeans   "Halo" means fluoro, chloro, bromo, or iodo.   "Hetero atom" means an atom selected from N, O, S and P.   "Heteroatom component" means -N =, -NR unless otherwise stated.¹⁷-, -O- , −S −, − S (O) −, − S (O)_Two−, −P (O) (OR¹⁷)-Means a component selected from , Where R¹⁷Is hydrogen or (C_1-6) Alkyl.   “Heteroalkyl” refers to an alkyl as defined above, with the proviso that One or more of the carbon atoms is a heteroatom as defined in the Detailed Description. Or any of its ketones, thioketones, or iminoketones Means a conductor (eg, hetero (C_2-12) Alkyl is methoxy, ethoxy, Ethylthio, 2- (2-methoxyethoxy) ethoxy, 3-methoxymethoxy Rubonylmethoxy, 2- (N-ethyl-N-methylamino) ethyl, 2-ethyl Iminoethyl, ethoxymethoxyphosphoryloxy, and the like. )   “Heteroalkylene” means alkylene as defined above, with the proviso that One or more of the carbon atoms is a heteroatom as defined in the Detailed Description. Component, or any suitable combination thereof (eg, -OS (O)_Two−, −S (O)_TwoO-, N (R) S (O)_Two−, S (O)_TwoNR¹⁷−, OP (O) (OR¹⁷) O- and the like (where R¹⁷Is hydrogen Or (C_1-6) Is substituted by) which is alkyl), and any of the keto Thioketone or imino ketone derivative (for example, hetero (C_2-10 ) Alkylene is azaethylene (-CH_TwoNH-), 2-azapropenylene (-CH_TwoN = CH_Two-), 1-oxatrimethylene (-CH_TwoCH_TwoO-), 2-oxa-3-azape Tamethylene, 3-aza-2-thiopentamethylene, 2-oxa-3-oxope Tamethylene, 3-aza-2-iminopentamethylene (-CH_TwoCH_TwoNHC (NH) CH_Two−) , 2,4-aza-2-methyl-3,3-dioxo-3-thiapentamethylene (- CH_TwoNHS (O)_TwoN (CH_Three) CH_Two-), 3-hydroxy-2,4-oxa-3-oxo-3 -Phosphapentamethylene (-CH_TwoOP (O) (OH) OCH_Two-), 3-aza-2-oxo- 4-carboxyhexamethylene, 4-aza-1-oxa-3-oxohexamethyl Len, 1-thia-3-oxo-4-azahexamethylene, 1-thia-1,1,3 -Trioxo-4-azahexamethylene (-CH_TwoCH_TwoNHC (O) CH_TwoS (O)_Two−), 3-A The-4-oxoheptamethylene, 1,4,7-trioxaoctamethylene, 6- Aza-1-oxa-2,5-dioxooctamethylene (—CH_TwoCH_TwoNHC (O) CH_TwoCH_TwoC ( O) O-), 3-aza-4-oxodecamethylene, and the like).   “Heteroaryl” refers to an aromatic unit having the number of ring atoms indicated. Means a ring or fused polycyclic divalent radical wherein the individual rings contained therein are from 5 to Consists of six ring members, and one or more of the ring members is -N =, -NR¹⁷-, -O Or a heteroatom component selected from -S-, wherein R¹⁷Is hydrogen or (C_1-6 ) Is alkyl and the individual rings contained therein are comprised of 5 to 6 ring members. (For example, hetero (C_5-14) Aryl is thioenyl, furyl, pyrrolyl, Pyrimidinyl, isoxazoyl, oxoxolyl, indolyl, benzo [b] thi Enyl, isobenzofuranyl, prenyl, isoquinolyl, pterdinyl, perimi Includes dinyl, imidazolyl, pyryl, pyrazolyl, pyrazinyl, quinolyl, etc. Including).   “Heterocycloalkyl” is cycloalkyl as defined above, with the proviso that And one or more of the indicated ring carbon atoms is as defined in the detailed description of the invention. Substituted by such a heteroatom moiety), and any of the carbocyclic ketones, A thioketone or imino ketone derivative (for example, the term heterocyclo ( C_5-14) Alkyl is piperidyl, hiroridinyl, pyrrolinyl, imidazolidinyl Quinuclidinyl, morpholinyl, and the like).   "Heterocycloalkylene" refers to a cycloalkylene as defined above (However, one or more of the indicated ring carbon atoms may be as defined in the detailed description of the invention. Substituted by such a heteroatom moiety), and any of the carbocyclic ketones, Including thioketone or imino ketone derivatives (eg, heterocyclo (C_{3- 14} ) Alkylene is piperidylene, pyrrolidinylene, pyrrolinylene, imidazolyl Dinylene, quinuclidinylene, morpholinylene, and the like).   “Heteropolycycloaryl” is a polycycloaryl as defined below. Wherein one or more of the indicated ring carbon atoms is defined in the Detailed Description of the Invention. Substituted by such a heteroatom component ) And its carbocyclic ketone, thioketone or imino ketone derivatives For example, heteropolycyclo (C_8-10) Alkyl is 3,4-dihydro-2H-ki Nolinyl, 5,6,7,8-tetrahydroquinolinyl, 3,4-dihydro-2H -[1,8] naphthyridinyl, 2,4-dioxo-3,4-dihydro-2H-ki Nazolinyl, 3-oxo-2,3-dihydrobenzo [1,4] oxazinyl, etc. ).   "Hydroxy" refers to the group -OH.   “Immune-mediated inflammatory diseases” involve the release of mast cell mediators and Those diseases that are sensitive to treatment with tryptase inhibitors (eg, Direct type hypersensitivity diseases such as asthma, allergic rhinitis, urticaria and edema , Eczema hypersensitivity, dermatitis such as atopic dermatitis, hyperproliferative skin disease, Ulcer, inflammatory bowel disease, ocular lens and conjunctivitis in spring, rheumatoid arthritis, inflammation Skin condition, and the like).   “Hyperresponsiveness” refers to late-phase bronchial stenosis and airway hyperreactivity associated with chronic asthma. Means responsive. Hyperreactivity of asthmatic bronchiole tissue lining the airway wall Stimulates and damages the epithelium and promotes pathological hypertrophy of the underlying tissue May be due to a chronic inflammatory response.   "Syncytium virus infection" refers to a virus Respiratory syncytia virus causing syncytial mass formation, ie syncytium Means infection.   "Imino" refers to the group -NH.   "Isomers" have the same molecular formula, but the nature of the bonding of their atoms Or compounds of formula I which differ in the arrangement or in the arrangement of their atoms in space Means things. Their source in space Isomers that differ in the arrangement of their children are termed “stereoisomers”. They are mirror images of each other Stereoisomers are called “diastereomers” and cannot be superimposed Stereoisomers that are mirror images are called "enantiomers" or "optical isomers." 4 The carbon atom attached to a single non-identical substituent is termed a "chiral center." One Having two chiral centers have two enantiomeric forms of opposite chirality , It is called a "racemic mixture". Compounds having one or more chiral centers are , 2^n-1(Where n is the number of chiral centers). One Compounds having the above chiral centers may be used as individual diastereomers or diastereomers. Exist as a mixture of stereomers (called a diastereomeric mixture) Can be. If one chiral center is present, the stereoisomer is the chiral center Can be characterized by the absolute configuration of Absolute configuration means that the Refer to the spatial configuration of the substituents. Substituents attached to a chiral center under consideration are Classified according to the Sequence Rule of Cahn, Ingold and Prelog, and absolute Descriptors R and S are quoted in parentheses, followed by a hyphen and the chemical name of the compound. U. Compounds of formula I containing a chiral center may be in the form of individual stereoisomers or a mixture of stereoisomers Can exist as things. For the purposes of this application, by name or by formula and distribution When no reference is made to a compound of formula I by way of configuration, all possible configurations of the compound It should be understood that mention is made.   “Optional” or “optionally” means that the phenomenon or situation described subsequently can exist. May or may not be possible, and the description indicates the fact that the phenomenon or situation exists. It is meant to encompass examples, and instances where they do not exist. For example, season "1 "Optionally substituted by three groups" means that the mentioned group is present within the scope of the present invention. As Means that it may or may not be substituted.   An “N-oxide derivative” is a compound in which the nitrogen is oxidized (ie, ON). And derivatives having the desired pharmacological activity. The N-oxide derivatives of the compounds of formula I are prepared by methods known to those skilled in the art. Can be   “Pathology” of “disease” refers to the substantial nature, causes and progression of the disease, and the disease. Means structural and functional changes caused by the process.   "Pharmaceutically acceptable" generally refers to the preparation of pharmaceutical compositions that are safe and non-toxic. And veterinary use, and human pharmaceutical use. Includes what is acceptable for   "Pharmaceutically acceptable salt" is pharmaceutically acceptable, as defined above. And a salt of the compound of formula I having the desired pharmacological activity. Like that Salts include the acid addition salts formed with the following acids: inorganic salts, such as Hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; or organic acids such as acetic acid , Propionic acid, hexanoic acid, heptanoic acid, cyclopentanepropionic acid, Relic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, Malic acid, tartaric acid, citric acid, benzoic acid, o- (4-hydroxybenzoyl) benzoic acid Perfume acid, cinnamic acid, maderic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-e Tandisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, p -Chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, p-toluenesulfo Acid, camphorsulfonic acid, 4-methylbicyclo [2.2.2] oct-2-ene- 1-carboxylic acid, glucoheptonic acid, 4,4'-methylenebis (3-hydroxy -2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, lauryl sulfate, gluconic acid, glutamic acid, hydroxynaph Toeic acid, sari Tylic acid, stearic acid, muconic acid, and the like.   Pharmaceutically acceptable salts also include those acidic protons present which react with inorganic or organic bases. Also included are base addition salts that may be formed where available. Acceptable inorganics Bases include sodium hydroxide, sodium carbonate, potassium hydroxide, aluminum hydroxide. And calcium hydroxide. Acceptable organic bases include ethanol Min, diethanolamine, triethanolamine, N-methylglucamine and Includes the same.   “Polycycloaryl” is a fused polycyclic group containing the indicated number of carbon atoms (Where not all, but not all, of the fused rings comprising said group are Aromatic and the individual rings contained therein are composed of 5 to 6 ring members ) And any of its carbocyclic ketone and thioketone derivatives (for example, For example, polycyclo (C_9-10) Aryl is indanyl, indenyl, 1,2,3 , 4-tetrahydronaphthyl, 1,2-dihydronaphthyl, 2,4-dioxo- 1,2,3,4-tetrahydronaphthyl, and the like).   “Prodrug derivative” refers to a compound of Formula I that is not correspondingly derived A derivative of a compound of Formula I that is converted in vivo to a form is meant. Proper prodrug The derivative is one or more nitrogen and / or oxygen sources having available free valences. Those of formula I, wherein the offspring are replaced by groups which can be easily degraded by in vivo processes Of the compounds. For example, a prodrug derivative of a compound of Formula I may have 1 or Multiple N-substituted amino groups (eg, -NH_Two(R¹⁸)), Aliphatic, cycloaliphatic or aromatic N-substituted nitrogen atoms introduced into the aromatic structure (eg, -N (R¹⁸)-), N- A substituted imino or amidino group (e.g., -C (NR¹⁸) H, −C (NR¹⁸) NH_TwoOr C (NH) NHR¹⁸), N-substituted Guanidino group (for example, -NHC (NR¹⁸) NHR¹⁸, −NHC (NH) NHR¹⁸Or -NHC (NR¹⁸ ) NH_Two), And the like, wherein the R¹⁸Is the following group: (I) -C (O) R¹⁹Or -CH (R²⁰) OC (O) R¹⁹, Where R¹⁹Is (C_1-10) Alkyl, ( C_1-10) Alkyloxy, carbamoyl, (C_1-10) Alkylcarbamoyl, di (C_1-10) Alkylcarbamoyl, cis-2- (C_1-10) Alkanoyloxyf Phenyl vinyl, 3- (C_1-10) Alkanoyloxybutyryl, (C_3-10) Cyclo Alkyl, hetero (C_3-10) Cycloalkyl, (C_6-10) Aryl or hetero ( C_5-10) Is aryl and R²⁰Is hydrogen or (C_1-10) Alkyl; ii) -X⁷-R^{twenty one}, Where X⁷Is (C_1-10) Is alkylene and R^{twenty one}Is Cal Or (iii) -C (O) OCH (R^{twenty two}) OC (O) R^{twenty three}, Where R^{twenty two}Is hydrogen, (C_{1 -Ten} ) Alkyl or (C_5-10) Is cycloalkyl and R^{twenty three}Is (C_1-10) Alkyl or (C_3-10) Cycloalkyl. In addition, the prod of the compound of formula I Lag derivatives may comprise one or more N-hydroxylated imino or amidino groups. (For example, -C (NOR^{twenty four}) H, −C (NOR^{twenty four}) NH_TwoOr -C (NH) NHOR^{twenty four}) Or N-hydroxy Silylated guanidino groups (eg -NHC (NOR^{twenty four}) NH_Two, -NHC (NH) NHOR^{twenty four}) (This Where R^{twenty four}Is hydrogen, methyl, -C (O) R^{twenty five}Or -CH (R²⁶) OC (O) R^{twenty five}Where R^{twenty five} Is (C_1-10) Alkyl or (C_3-10) Is cycloalkyl and R²⁶Is hydrogen Or (C_1-10) Alkyl)); N-substituted hydroxy groups (eg, -OR²⁷ ) (Where R²⁷Is -C (O) R¹⁹Or -CH (R²⁰) OC (O) R¹⁹Where R¹⁹And R²⁰ Is as defined above); and / or an ester derivative of a carboxylic acid ( For example, -C (O) OR²⁸) (Where R²⁸Is (C_1-10) Alkyl or (C_3-10) Cyclo Which is alkyl).   “Protecting group” has the meaning normally associated with it in synthetic organic chemistry Ie, the chemical reaction is selective at another unprotected reactive site Blocking one reactive site in a polyfunctional compound so that it can be implemented And a group that can be easily removed after the selective reaction is completed.   “Protected derivative” refers to a compound in which the reactive site is blocked by a protecting group. A derivative of the compound of I is meant. Protected derivatives of the compounds of formula I are Useful in preparing compounds. A suitable protecting group for a reactive nitrogen atom is tert. -Butoxycarbonyl, benzyloxycarbonyl, and any other suitable Includes amino protecting groups (eg, T.W. Greene, Protective Groups in Orgoni c Synthesis, John Wiley & Sons, Inc. 1981). In particular, the formula I A sharp protected derivative is the compound 2- [5- (1,3-dioxo-1,3-di- (Hydroisoindol-2-ylmethyl) -1H-benzimidazol-2-i Methyl-4,5,6,7-tetrahydro-1H-benzimidazole-5 Exemplified by carboxylic acids.   A "therapeutically effective amount", when administered to an animal, is effective for treating the disease. Means an amount.   "Treatment" or "treating" means the administration of any of the compounds of the present invention, And   (1) may be predisposed to the disease, but the pathology or signs of the disease Prevent the development of disease in animals that are still experiencing or exhibiting;   (2) prevent the disease, ie, inhibit the progression of its pathology and / or signs; Is   (3) relieve the disease, ie reverse its pathology and / or signs;   It is included.   "Sulfo" refers to the group -S (O) OH.   “Uriedo” refers to the group —NHC (O) NH_TwoMeans   The compounds of formula I, and the intermediates and starting materials used in their preparation, are named Named according to IUPAC rules of the law. For example, a compound of formula I having the following components They are named as follows:   A together with B is 5-guanidino-1H-benzimidazol-2-yl Wherein C is 5- (2-naphth-1-ylethylcarbamoyl) -1H-benzen Constitutes zimidazol-2-yl; and X^ThreeIs -CH_TwoWherein the compound of formula I is , 2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -N- (2-Naphth-1-ylethyl-1H-benzimidazole-5-carboxami Named   A is combined with B to form 5-guanidino-1H-benzimidazol-2-yl Wherein C is 6- (2-naphth-1-ylethylcarbamoyl) -1-methyl -1H-benzimidazol-2-yl; and X^ThreeIs -CH_TwoFormula I which is Is 2- (5-guanidino-1H-benzimidazol-2-ylmethyi) ) -3-Methyl-N- (2-naphth-1-ylethyl-3H-benzimidazo No. 5-carboxamide;   A is combined with B to form 5-guanidino-1H-benzimidazol-2-yl Wherein C is 6- [2- (2-carboxyphenyl) ethylcarbamoyl]- Constituting 1- (3-sulfopropyl-1H-benzimidazol-2-yl; Then X^ThreeIs -CH_Two-Is a compound of the formula I 2- {2- [2- (5-guanidino- 1H-benzimidazol-2-ylmethyl) -3- (3-sulfopropyl)- 3H-benzimidazol-5-ylcarbonylamino] ethyl さ れ named benzoic acid; and   A is combined with B to form 5-guanidino-1H-benzimidazol-2-yl Wherein C is 6- [2- (2-methoxyphenyl) ethylcarbamoyl] -1 -(3-sulfopropyl-1H-benzimidazol-2-yl; X^ThreeIs -CH_TwoIs a compound of formula I, which is 3- (2- (5-guanidino-1H-be Zonzimidazol-2-ylmethyl) -6- [2- (2-methoxyphenyl) e Tylcarbamoyl] benzimidazol-1-yl) propane-1-sulfonic acid It is named.   Certain compounds of formula I exist in tautomeric equilibrium. For example, if C is 4,5 6,7-tetrahydro-3H-imidazo [4,5-c] pyridin-2-yl The resulting compound of formula I exists in equilibrium between tautomers of the formula: And, therefore, the compounds of the present invention are described in the present application as one possible tautomer. May be named, exemplified, or, on the other hand, described. It is reasonable to mean that a variant is encompassed by such a name, illustration and description. Should be understood. Accordingly, the name ethyl 2- (4- {2- [1- (5-gua Nidino-1H -Benzimidazol-2-yl) ethyl] -1,4,6,7-tetrahydroi Midazo [4,5-c] pyridin-5-yl {-4-oxobutyl) benzoate Is a tautomer thereof, ethyl 2- (4- {2- [1- (5-guanidino-3H-beta) Nzonimidazol-2-yl) ethyl] -1,4,6,7-tetrahydroimida Zo [4,5-c] pyridin-5-yl {-4-oxobutyl) benzoate, Cyl 2- (4- {2- [1- (5-guanidino-1H-benzimidazole-2) -Yl) ethyl] -3,4,6,7-tetrahydroimidazo [4,5-c] pyri Zin-5-yl {-4-oxobutyl) benzoate and ethyl 2- (4- { 2- [1- (5-guanidino-3H-benzimidazol-2-yl) ethyl] -3,4,6,7-tetrahydroimidazo [4,5-c] pyridin-5-yl} -4-oxobutyl) benzoate. Currently preferred embodiments:   While the broadest definition of the invention is set forth in the summary, certain aspects of the invention are provided. Is preferred. A preferred aspect of the invention is that A is a complex complex fused together with B A compound of formula I constituting a cyclic group wherein A contains 5 ring members and B is 6 And X^FourAnd X^FiveIs oxazol-2-yl, 1H-imidazo 2-yl or adjacent members of the thiazol-2-yl ring) You.   A preferred aspect of the present invention is a compound of formula II: [Wherein the dotted lines may independently represent any bond;   Individual R^TwoAre independently (C_1-6) Alkyl, (C_1-6) Alkyloxy, halo Or hydroxy;   Individual R^ThreeAre independently (C_1-6) Alkyl, (C_1-6) Alkyloxy, halo Or hydroxy;   X^ThreeIs -C (O)-or -CR⁷R⁸-   X⁸Is --CH (R¹)_n1-Or -C (R¹)_n1-Where R¹Is amino (N_1-4A) Zolidinyl, amino (N_1-4) Azolyl, (N₁₄) Azolidinyl, (N_1-4) Azo Lil, -NHC (NH) NR⁹R⁹, −C (NR⁹) R⁹, −C (NH) NHR^Ten, −C (NH) NR^TenR^TenOr-(CR^{1 1} R¹¹)_yNH_zOr X⁸Is -N = or -NH (R¹)_n1-Where R¹Is −C (NR⁹) R⁹, −C (NH) NHR^TenOr -C (NH) NR^TenR^TenWhere each individual R⁹Is independent And hydrogen or (C_1-6) Is alkyl and each R^TenAre independently (C_1-6 ) Alkyl; and   X⁹Is --CH (R^Four)-Or -C (R^Four) =, Where R^FourIs -R¹², −OR¹², −N (R¹³ ) R¹², −SR¹², −S (O) R¹², −S (O)_TwoR¹², −S (O)_TwoOR¹², −S (O)_TwoN (R¹³) R¹², −N ( R¹³) S (O)_TwoR¹², −C (O) R¹², −C (O) OR¹², −C (O) N (R¹³) R¹², −N (R¹³) C (O) R¹², −OC (O) N (R¹³) R¹², −N (R¹³) C (O) OR¹², − (CH_Two)_n4N (R¹³) C (O) N (R¹³) R¹², −OP (O ) (OR¹³) OR¹²Or -C (O) N (R¹⁴) CH (COOH) R¹²Or X⁹Is -N = or -N (R^Four)-Where R^FourIs -C (O) R¹², −C (O) OR¹², −C (O) N (R¹³) R¹², −OC (O) N (R¹³) R¹²Or -C (O) N (R¹⁴) CH (COOH) R¹²Where R¹², R¹³And R¹⁴Departs As defined in the Summary of the Invention].   A preferred aspect of the invention is a compound of formula I: [Wherein, R^FiveIs hydrogen, or (C_1-4) Alkyl;⁶Is hydrogen or (C_1-4A) And the alkyl is optionally (C_1-4 1) 1-2 positions independently selected from alkyloxy, hydroxy and sulfo May be substituted by a substituent⁷Is hydrogen or methyl, and R⁸Is water Hydrogen, methyl or hydroxy;   X⁸Is --CH (R^Four)-Or -C (R¹)_n1= Where R¹Is aminomethyl, 1-A Minocyclopropyl, 2-aminoimidazol-1-yl, 2-amino-1,1 -Dimethylethyl, imidazolyl, tetrazolyl,-(CH_Two)_xNHC (NR⁹) R⁹, − (CH_Two )_xNHC (NH) NR⁹R⁹And -C (NR⁹) R⁹Where each individual R⁹Are independently hydrogen or Chill or X⁸Is −N (R¹)_n1= Where R¹Is -C (NR⁹) R⁹, −C (N H) NHR^TenOr -C (NH) NR^TenR^TenWhere each individual R⁹Is independently hydrogen or methyl And each R^TenIs methyl, where R¹Any of which constitutes The aliphatic or cycloaliphatic component is independently selected from methylsulfonyl and carboxy. Optionally substituted by one or two substituents;   X⁹Is -C (R^Four) =, Where R^FourIs -R¹², −OR¹², −C (O) R¹², −C (O) OR¹² , −C (O) N (R¹³) R¹²Or -C (O) N (R¹⁴) CH (COOH) R¹²Where R¹³And R¹⁴Is Independently, hydrogen or (C_1-6) Is alkyl;¹²Is -R^FifteenOr -X⁶− (R^Fifteen)_{n Fifteen} Where X⁶Is (C_1-10) Alkylene or hetero (C_2-10) Alkylene And the individual R^FifteenIs independently hydrogen, (C_6-14) Aryl, cyclo (C_3-14 ) Alkyl, polycyclo (C_6-14) Aryl, heterocyclo (C_3-14) Ant Or hetero (C_5-14) Is aryl;   R^FourIs any of the aliphatic or cycloaliphatic components_1-4) Alkyloxy , (C_1-4) Alkyloxycarbonyl, amino, carbamoyl, carboxy and And optionally substituted with 1 to 5 substituents independently selected from hydroxy May be; and   R^FifteenIs any of the aromatic components (C_1-4) Alkyl, (C_1-4) Al Killoxy, (C_1-4) Alkyloxycarbonyl, carbamoyl, carboxy , Cyano, cyclo (C_3-6) Alkyloxy, halo, hetero (C_1-8) Alkyl, Hetero (C_1-8) Alkylcarbonyl, hetero (C_5-6) Aryl and trifluoro Optionally substituted with 1 to 3 substituents independently selected from And N-oxide derivatives and prodrugs thereof. Conductors, protected derivatives, individual isomers, mixtures of isomers, and pharmaceutically acceptable It is a salt that can be cut.   A preferred aspect of the invention is a compound of formula I: Wherein A is taken together with B to form 4,5,6,7-tetrahydro-1H-imid Constitutes dazo [4,5-c] pyridin-2-yl, wherein n2 is 0 and R¹Is -C (NR⁹) R⁹Or A together with B is 1H-benzoyl Midazol-2-yl or 4,5,6,7-tetrahydro-1H-benzimida Constitutes 2-zol-2-yl, where R¹Is aminomethyl or guanidino, And individual R¹Is independently halo, or hydroxy;   C is 4,5,6,7-tetrahydro-1H-imidazo [4,5-c] pyridi Or 1H-benzimidazol-2-yl, where R^FourIs −C (O) X⁶-R^Fifteen, −C (O) OX⁶-R^FifteenOr -C (O) NHX⁶-R^FifteenWhere X⁶Is ( C_1-4) Alkylene or hetero (C_2-4) Is alkylene and R^FifteenIs (C_{6- Ten} ) Aryl, (C_6-10) Aryloxy, polycyclo (C_6-10) Aryl, f Terrorism (C_5-10) Aryl, hetero (C_5-10) Aryloxy or heteropolycyclyl B (C_6-14) Aryl; and   R^FifteenIs any of the aromatic components (C_1-4) Alkyl, (C_1-4) Al Killoxy, (C_1-4) Alkyloxycarbonyl , Carboxy, carbamoyl, halo, hydroxy and tetrazol-1-yl May be optionally substituted by 1 to 3 substituents independently selected from A compound represented by the formula; and N-oxide derivatives, prodrug derivatives and protection thereof. Derivatives, individual isomers, mixtures of isomers and pharmaceutically acceptable salts .   A preferred aspect of the invention is that n1 is 0 and each R^TwoBut independently, ha Compounds of formula I which are b or hydroxy, especially the following compounds:   2- (2- {2- [1- (4,6,7-trifluoro-1H-benzimidazo) 2-yl) ethyl] -3-methyl-3H-benzimidazol-5-yl Carbonylaminodiethoxy) benzoic acid;   2- (2- {2- [1- (5,6-difluoro-1H-benzimidazole- 2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcarbo Nilaminodiethoxy) benzoic acid;   Butyl 2- (2- {2- [1- (5-hydroxy-1H-benzimidazole) -2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcar Bonylaminodiethoxy) benzoate;   Propyl 2- (2- {2- [1- (5-hydroxy-1H-benzimidazo) Ru-2-yl) ethyl] -3-methyl-3H-benzimidazol-5-dolphin Rubonylaminodiethoxy) benzoate; and   Isobutyl 2- (2- {2- [1- (5-hydroxy-1H-benzimidazo) 2-yl) ethyl] -3-methyl-3H-benzimidazol-5-yl Carbonylaminodiethoxy) benzoate.   A preferred aspect of the present invention is that R¹Is a compound of formula I wherein is aminomethyl or guanidino Compounds, especially the following compounds:   2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- Methyl-N- (2-naphth-1-ylethyl) -3H-benzimidazole-5 -Carboxamide;   Ethyl 2- (4- {2- [1- (5-guanidino-1H-benzimidazole) -2-yl) ethyl] -1,4,6,7-tetrahydroimidazo [4,5-c] Pyridin-5-yl {-4-oxobutyl) benzoate;   2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- (2,3-dihydroxy) propyl-N- (2-naphth-1-ylethyl) -3 H-benzimidazole-5-carboxamide;   2- (5-guanidino-1H-benzimidazol-2-ylcarbonyl)- 3- (2,3-dihydroxy) propyl-N- (2-naphth-1-ylethyl) -3H-benzimidazole-5-carboxamide;   2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- (3-Hydroxy) propyl-N- (2-naphth-1-ylethyl) -3H-be Nzoimidazole-5-carboxamide;   2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- (2-hydroxy) ethyl-N- (2-naphth-1-ylethyl) -3H-ben Zoimidazole-5-carboxamide;   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -N- [2- (2-carbamoylphenoxy) ethyl] -3-methyl-3H- Benzimidazole-5-carboxami Do;   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -N- [2- (2-carbamoyl-4-chlorophenoxy) ethyl] -3-me Tyl-3H-benzimidazole-5-carboxamide;   4-chloro-2- [2-({2- [1- (5-guanidino-1H-benzoimid) Dazol-2-yl) ethyl] -3-methyl-3H-benzimidazol-5 Ylcarbonyl {amino) ethoxy] benzoic acid;   5-chloro-2- [2-({2- [1- (5-guanidino-1H-benziimi) Dazol-2-yl) ethyl] -3-methyl-3H-benzimidazol-5 Ylcarbonyl {amino) ethoxy] benzoic acid;   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -3 -Methyl-N- (2-naphth-1-ylethyl) -3H-benzimidazole- 5-carboxamide; and   2- (5-aminomethyl-4,5,6,7-tetrahydro-1H-benzoimid Dazol-2-ylmethyl) -3-methyl-N- (2-naphth-1-ylethyl ) -3H-Benzimidazole-5-carboxamide.   A preferred aspect of the present invention is that C is 4,5,6,7-tetrahydro-1H-imida. Zo [4,5-c] pyridin-2-yl constitutes¹Is -C (NH) R⁹Expression that is Compounds of I, in particular the following compounds:   2- [2- (2- {1- [5- (1-iminoethyl) -4,5,6,7-tetra] Lahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3- Methyl-3H-benzimidazol-5-ylcarbonylamino) ethoxy] an Benzoic acid;   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- (2-na Fut-1-ylethyl) -3H-benzimidazole-5-carboxamide;   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylcarbonyl] -3-methyl-N- (2 -Naphth-1-ylethyl) -3H-benzimidazole-5-carboxamide ;   2- (5-iminoethyl) -4,5,6,7-tetrahydro-1H-imidazo [4,5-c] pyridin-2-ylmethyl) -3-methyl-N- (2-naphtho- 1-ylethyl) -3H-benzimidazole-5-carboxamide;   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- (2-h Droxy-2-naphth-1-ylethyl) -3H-benzimidazole-5-ca Ruboxamide;   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- [2- ( 2-hydroxynaphth-1-yl) ethyl] -3H-benzimidazole-5 Carboxamide;   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- [2- ( 4-hydroxynaphth-1-yl) ethyl] -3H-benzimidazole-5 Carboxamide;   2- {1- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1 H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3-methyl-N- (2-Naphth-1-ylethyl) -3H -Benzimidazole-5-carboxamide;   Ethyl 2- [2- (2- {1- [5- (1-iminoethyl) -4,5,6,7 -Tetrahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl -3-methyl-3H-benzimidazol-5-ylcarbonylamino) ethoxy B) benzoate;   2- [2- (2- {1- [5- (1-iminoethyl) -4,5,6,7-tetra] Lahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3- (2-methoxyethyl) -3H-benzimidazol-5-ylcarbonylamido G) ethoxy] benzoic acid;   Ethyl 2- [2- (2- {1- [5- (1-iminoethyl) -4,5,6,7 -Tetrahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl -1,4,6,7-tetrahydroimidazo [4,5-c] pyridin-5-dolphin Rubonylamino) ethoxy] benzoate; and   2- {1- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1 H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3-methyl-N- [2- (2-tetrazolylphenoxy) ethyl] -3H-benzimidazole- 5-carboxamide. Pharmacology and uses:   The compounds of the present invention are serine protease inhibitors and as such , Useful in treating diseases associated with increased serine protease activity. Special In addition, the compounds of the present invention are tryptase inhibitors, and tryptase Useful in treating diseases associated with increased activity. Inhibits tryptase Screening for potential inhibitors of their ability Vitro protocols are known in the art. For example, Sturzebecher. (1992) Biol. Chem. Hoppe-Seyler 373: 1025-1030 checking ... Typically, those assays are based on peptide-based chromogenic substances. Enzyme-induced hydrolysis is measured. For measuring tryptase inhibitory activity Details of an exemplary method are described below.   In addition, the activity of the compounds of the present invention has been demonstrated in one of many animal models of asthma. It can be evaluated in vivo. Larson, “Experimental Models of Reversible Airw ay Obstruction ”, in The Lung: Scientific Foundations, Crystal, West, etc. . Eds., Raven Press, New York, 1991; Warner et al. (1990) Am. Rev. Resp ir. Dis. See 141: 253-257. The ideal animal model follows human asthma Will reproduce key clinical and physiological characteristics such as: chemical mediators Hyperresponsiveness of airways to physical and physical stimuli; drugs useful in human asthma (Β-adrenergic agents, methylxanthine, corticosteroids, and Reversal of airway obstruction; airway inflammation due to infiltration of activated leukocytes; And chronic inflammatory degradative changes such as hypertrophy of basement membrane, hypertrophy of smooth muscle, and epithelial damage Wounds. Species used as animal models include mice, rats, guinea pigs, Includes herons, dogs, and sheep. All have some limitations and animal models Dell's correct choice depends on the problem to be addressed.   The early asthmatic response is evident in guinea pigs and dogs, especially many non-allergic substances. Promotes nonspecific airway hyperresponsiveness to, for example, methacholine and citrate Can be evaluated in basenji-greyhound cross species. Certain selected sheep A double response is shown after antigen challenge with Ascaris protein. Double answer In responders, the early asthmatic response (LAR) was followed by a 6-8 hour exposure followed by a late Accompanied by asthmatic response (LAR). To the cholinergic agonist carbachol Hypersensitivity increases 24 hours after antigen challenge in those animals displaying LAR .   Allergic sheep model (see below) may be a potential compound of the invention It was used to evaluate the sedative effect of asthma. Before exposure to certain allergens or Subsequently, to allergic sheep both by oral and inhalation or aerosol formulation The administration of a composition comprising a compound of the invention of the invention may be such that such a composition is in late asthma Indicate that response and subsequent hyperresponsiveness are substantially reduced or abolished.   The compounds of the present invention may also include other compounds in which tryptase activity contributes to its pathological condition. It is also useful for treating immune-mediated inflammatory diseases. Such diseases are obese Inflammatory diseases involving the vesicles, such as rheumatoid arthritis, conjunctivitis, rheumatic back phase Inflammation, osteoarthritis, gouty arthritis, and other arthritic conditions, inflammatory bowel disease, peptic Includes ulcers and various skin conditions. Further, the compounds of the present invention may comprise syncytium It can also be used to treat viral infections.   The efficacy of the compounds of the invention for the treatment of most immune-mediated inflammatory diseases is It can be assessed by either in vitro or in vivo processes. Therefore, the compound of the present invention The anti-inflammatory efficacy of the product can be determined by assays known in the art, for example, Revers. ed Passive Arthus Reaction (RPAR) -PAW technique (for example, Gangly et al. (1992) See US Pat. No. 5,126,352). Various skin conditions, For example, to determine the therapeutic value of a compound in the treatment of hyperproliferative skin diseases Assays, such as the Arachidonic Acid Mouse Ear Test (supra), are Well-known. Compounds of the present invention are described in Chiu et al. (1984) Archives Interna method described in nationes de Pharmacodynamie et de Therapie 270: 128-140 Can be evaluated for their anti-ulcer activity.   Primary in blocking cell fusion caused by syncytium virus infection The efficacy of the compounds of Ming, Tidwell, et al. , J. et al. Med. Chem. 26: 294-298 (1983) It can be evaluated by the method generally shown. Composition and administration:   According to the present invention, a therapeutically or pharmaceutically effective amount of a compound of the present invention is administered to an immune-mediated Administered to patients with underlying inflammatory disease. According to one aspect, the composition of the present invention Is useful for preventing or relieving asthma. The present invention for the treatment of asthma In the use of the composition of the invention, the compounds of the invention are Can be administered prophylactically before or after such exposure. Compound of the present invention Is particularly useful in reversing late phase tissue destruction seen in seasonal and permanent rhinitis. It is for. Another aspect of the present invention relates to other immune-mediated inflammation associated with mast cells. Dermatitis, such as urticaria and edema, and eczema dermatitis (atopic dermatitis), For the prevention and treatment of irritable, hyperproliferative skin diseases, peptic ulcers, and the like. Be killed. In yet another aspect, the compound of the present invention comprises syncytium Used to treat viral infections, especially respiratory syncytial virus infections You.   Compositions comprising a compound of the present invention may be administered for therapeutic and / or prophylactic treatment. You. In therapeutic applications, the composition is useful for patients who already have the disease as described above. To cure or at least partially arrest the symptoms of the disease and its complications It is administered in a sufficient amount. Suitable amounts to achieve this are “therapeutically effective amounts or The effective amount for this use is defined as the severity and course of the disease, Prior therapy, patient health, and drug responsiveness, and the judgment of the treating physician Will depend on the interruption.   In prophylactic applications, compositions containing the compounds of the present invention are susceptible to certain diseases. In patients who are sensitive or at risk, sufficient to prevent or reverse the onset of symptoms Is administered. Such an amount is defined as a "prophylactically effective amount or dose." They can be administered orally or by inhalation. In this application, its exact The exact amount will again depend on the patient's condition, such as health, weight and the like.   When an improvement in the patient's condition occurs, a maintenance dose is administered, if necessary. as a result, Dosage or frequency of administration, or both, remain improved as a function of symptoms. Can be lowered to a level. If symptoms return to the desired level, processing stops. Can be stopped. However, patients are not treated based on any recurrence of disease symptoms. Requires long-term intermittent processing.   In general, a suitable effective dose of a compound of the invention will be from 0.05 to 1000 mg / recipient / day; Preferably it will be present in the range 0.1-100 mg / day. The desired dose is preferred Or 1, 2, 3, 4 or more sub-doses administered at appropriate intervals during the day. Provided in doses. Their sub-dose is 0.01-1000 mg per unit dosage form, preferably Or it may be administered as a unit dosage form containing from 0.01 to 100 mg of the active ingredient.   The compositions used for these treatments can be in various forms. It Include, for example, solid, semi-solid and liquid dosage forms, such as tablets, enteric-coated tablets Including pills, powders, liquid solutions or suspensions, liposomes, injectable and wetting solutions I do. Preparations for inhalation, such as aerosols, are also included. Preferred formulations are Formulation intended for oral, intranasal, topical or parenteral use, but The preferred form will depend on the particular therapeutic application manually. Particularly preferred formulation The object is oral or aerosol. Delivery of a therapeutic composition comprising a compound of the present invention Methods for synthesis and preparation are known in the art. And well-known, for example, Remington's Pharmaceutocal Science s and The Merck Index 11th Ed., (Merck & Co. 1989).   While it is possible for the active ingredient of the present invention to be administered alone, it can be administered as part of a pharmaceutical formulation. Is preferably present. The formulation of the present invention may be a pharmacologically acceptable carrier. Together with at least one compound described herein, therapeutically or pharmaceutically An effective dose. Accordingly, the pharmaceutical compositions may provide a compound of the present invention in a suitable It will contain enough concentration to provide a dose. For example, a suitable dose of 0.05 mg / Day, the concentration of the compound of the invention in the pharmaceutical composition is 0.05 mg / dose. Here, a single dose per day is used. For inhalation or aerosol compositions In general, the concentration of a compound of the invention in a composition will generally be Will depend. Typical Compounds of the Invention in Inhalation or Aerosol Compositions Suitable concentrations are from about 0.01 to about 30 mg / ml. The formulation contains other clinically useful compounds, For example, β-adrenergic substances (eg, aldethylol, terbutaline, Formoterol, fenoterol and pernalin) and corticosteroids ( For example, beclomethasone, triamcinolone, flunisolide and dexamethasone ) Can be included. Chemistry:   In general, the compounds of the present invention can be prepared by standard techniques known and used by those skilled in the art and It is synthesized using reagents. The linkage between the various functional groups is generally The carbon linked to the nitrogen of the bamate, the oxygen of the carbamate or the carbon of the carbonyl Generally comprises. One skilled in the art will recognize that methods and reagents for forming those bonds are It will be known to be well known and readily available. For example March, Advancbd Orbanic Chemistry, 4th Ed. (Wiley 1992), L arock, Comprehensive Oroanic Transformations (VCH 1989); and Furniss, e t al., Vogel's Textbook of Practical Organic Chemistry 5th ed. (Longman  1989) (incorporated herein by reference).   X^FourAnd X^FiveIs oxazol-2-yl, 1H-imidazol-2-yl or Compounds of Formula I, which are adjacent members of the azole-2-yl ring, are reacted as described below. Can be produced by the method shown in the following scheme:                                Scheme 1   Where L is a leaving group and D is together with the vinylene moiety to which it is fused. Thus, comprising 5 to 15 ring atoms, constituting a monocyclic or fused bicyclic divalent group, Wherein each group contains from 5 to 7 ring atoms, and each ring atom is optionally May be a heteroatom, R²⁹Is -OH, -NHR⁶Or -SH and X^FourIs -O- , −NR⁶-Or -S-, and n2, n3, n4, A, B, X¹, X^Two, X^Three, X^Five, R¹, R^Two, R^Three, R^FourAnd R⁶Is as defined in the Summary of the Invention It is.   X^FourAnd X^FiveIs oxazol-2-yl, 1H-imidazol-2-yl or Compounds of Formula I (Formula I (a)), which are adjacent members of the azole-2-yl ring, are Compounds of formula I or protected derivatives thereof and compounds of formula 2 or protected derivatives thereof React with body and then, if necessary, prepared by deprotection be able to. The reaction between Equation 1 and Equation 2 can be performed straightforward, But preferably 1,3-dimethyl-3,4,5,6-tetrahydro-2 ( 1H) -Pyrimidinone (DMPU) or polyphosphoric acid at 160-200 ° C, preferably Or 180-190 ° C and requires 1-5 hours to complete (Eg, Examples 4 (d), 6 (h), 8 (k), 9 (d) and 10 (d) See). Deprotection removes the protecting groups and gives the desired yield in the reaction yield. Can be provided by any means that results in a product (see, eg, Example 2 (g)). See).   In a similar manner, X¹And X^TwoIs oxazol-2-yl, 1H-imidazole -2-yl or a compound of formula I that is a neighboring member of the thiazol-2-yl ring It can be prepared by the method shown in the following reaction scheme:                                Scheme 2  Where L is a leaving group and R³⁰Is -OH, -NHR^FiveOr -SH and X⁸Is -O −, NR⁶Or -S-, and n2, n3, n4, B, C, X¹, X^Three, X^Four , X^Five, R¹, R^Two, R^Three, R^FourAnd R⁶Is as defined in the Summary of the Invention. See, for example, Examples 2 (e) and 7 (h)).   Isolation and purification of the compounds and intermediates described herein may be performed, if necessary, at any time. Suitable separation or purification methods, such as filtration, extraction, crystallization, column chromatography Laffy, thin layer chromatography or thick layer chromatography, high pressure liquid chromatography It can be provided by chromatography (HPLC) or a combination of these methods. Suitable Specific illustrations of intelligent separation and isolation methods are mentioned in the examples below. However, mochi Of course, other equivalent separation or isolation methods may be used. Nuclear magnetic resonance (NMR) spectrum Was recorded on a General Electric "QE Plus" spectrometer (300 MHz). Infrared (IR) spectra were recorded on a Perkin-Elmer 1600 Fourier Transform IR (PTIR). It was recorded. Analytical HPLC is 1 Ultrafast Microprotein Analyzer, equipped with a mm x 150 mm PLRP column, Michrom BioResources, Inc. Implemented above. HPLC for separation is VYDAC 1 × 25cm   C₁₈On a Gilson LC using a reverse phase (RP) column or Vydac 5 × 25 cm C₁₈RP The test was performed on a Waters Prep LC 2000 system using a column. Mass spectrum (MS) is by direct injection or HPLC MS (Ultrafost Microprotein Analyzer, C₁₈ (Column 2 mm x 150 mm) on a Finnigan SSQ 710 with an ESI source. In particular Unless otherwise stated, all reagents and equipment were prepared according to published methods. Or commercial sources such as Aldrich Chemical Co. (Milwaukee, WI), Sigma Chemic al Co. (St. Louis, MO) and ICN Chemical Co. (Irvine, CA) . The techniques used to carry out the following syntheses will be understood by those skilled in the art. (Eg, March, Larock or Furnise, see above). Additional methods for preparing compounds of Formula I:   Compounds of formula I are compatible with the free base form of the compound of formula I and pharmaceutically acceptable inorganic or organic compounds. Prepared as a pharmaceutically acceptable acid addition salt by reacting Can be On the other hand, pharmaceutically acceptable base addition salts of compounds of formula I Reacting the free acid form of the compound with a pharmaceutically acceptable inorganic or organic base. Thus it can be prepared. Suitable for the preparation of pharmaceutically acceptable salts of the compounds of formula I Various inorganic and organic acids and bases are set forth in the Definitions section herein. On the other hand, the formula I Can be prepared using salts of the starting materials or intermediates.   The free acid or free base form of the compound of Formula I is prepared according to its corresponding base addition salt or acid addition It can be prepared from the salt form. For example, a compound of Formula I in an acid addition salt form may be prepared using a suitable base (Eg, ammonium hydroxide solution, sodium hydroxide, etc.) By doing so, To the free base. Compounds of formula I in base addition salt form may be prepared by treating the appropriate acid (eg, For example, hydrochloric acid, etc.) to convert to the corresponding free acid. You.   The N-oxides of formula I can be prepared by methods known to those skilled in the art. And For example, N-oxides convert the unoxidized form of the compound of formula I to an oxidizing agent (eg, For example, trifluoroperacetic acid, permaleic acid, perbenzoic acid, peracetic acid, meta-chloroper Oxybenzoic acid, etc.) with a suitable inert organic solvent (eg, halogenated Prepared at about 0 ° C. under purified hydrocarbon (eg, methylene chloride) Can be done. On the other hand, the N-oxides of the compounds of the formula I Can be produced from   Compounds of formula I in unoxidized form can be prepared using a suitable inert organic solvent (eg, Acetonitrile, ethanol, aqueous dioxane, etc.) Sulfur, sulfur dioxide, triphenylphosphine, lithium borohydride, sodium borohydride Thorium, phosphorus trichloride, tribromide, etc.) at 0 to 80 ° C. Thus, they can be prepared from N-oxides of the compounds of the formula I.   Prodrug derivatives of the compounds of formula I can be prepared by methods known to those skilled in the art. (Eg, see Example 12). Brodrugs and their preparation See Saulnier et al. For more details. (1994), Bioorganic and Medic inal Chemistry Letters, 4: 1985).   Protected derivatives of the compounds of formula I may be prepared by means known to those skilled in the art. Can be A detailed description of techniques applicable to the creation of protecting groups and their removal can be found in T.W. . Greene, Protective Groups in Organic Synthesis, John Wiley & Sons, Inc . 1981.   Compounds of formula I form a pair of diastereomeric compounds Then, an optically active decomposer is reacted with a racemic mixture of By separating the omer and recovering the optically pure enantiomer, They can be prepared as their individual stereoisomers. The resolution of the enantiomer is determined by the compound of formula I Can be carried out using covalent diastereomeric derivatives of Preferred (eg, crystalline diastereomeric salts). Diastereomers are different Physical properties (eg, melting point, boiling point, solubility, reactivity, etc.) and It can be easily separated by taking advantage of the nature. Diastereomers are chromatographic By chromatography or, preferably, by separation / lysis techniques based on differences in solubility. Can be separated. Next, the optically pure enantiomer, along with the resolving agent, is racemized. Is recovered by any means of implementation that does not result in A racemic mixture of them A more detailed description of techniques applicable to the resolution of stereoisomers of these compounds can be found in Jean Jac ques Audre Collet, Samuel H. Wiler, Enantiomers, Racemates and Resolution s, Honh Wiley & Sons, Inc. (1981).   In summary, an aspect of the present invention relates to a method for preparing a compound of formula I, Here the method is:   (A) Formula 1: Wherein L is a leaving group and n1, n2, A, B, X¹, X^Two, X^Three, R¹Passing And R^TwoIs as defined in the Summary of the Invention] And a protected derivative having the formula 2: Wherein D is, together with the vinylene component to which it is fused, 5 to 15 ring atoms A monocyclic or fused bicyclic divalent group comprising: wherein each ring is from 5 to 7 rings Atoms and individual ring atoms can optionally be heteroatoms;²⁹ Is -OH, -NHR⁶Or -SH and n3, R^Three, R^Four, R⁶Is included in the abstract of the invention. As defined above], or a protected derivative thereof. And then, if necessary, deprotect and X^FourAnd X^FiveIs oxazol-2-yl A compound of formula I which is a 1H-imidazol-2-yl or thiazol-2-yl ring Bring things; or   (B) Formula 3 below: Wherein L is a leaving group and C, n3, X^Three, X^Five, R^ThreeAnd R^FourIs the key to invention As defined above) or a protected derivative thereof; Equation 4 below: [Wherein, R³⁰Is -OH, -NHR^FiveOr -SH, and n1, n2, B, R¹, R^Two And R^FiveIs as defined in the summary of the invention) Reacting the compound represented or a protected derivative thereof, and if necessary, Deprotect and X¹And X^TwoIs oxazol-2-yl, 1H-imidazole-2-i Or a neighboring member of the thiazol-2-yl ring. Let;   (C) optionally further converting the compound of formula I to a pharmaceutically acceptable salt;   (D) optionally further converting the salt form of the compound of formula I to a non-salt form;   (E) optionally further comprises the pharmaceutically acceptable unoxidized form of the compound of formula I To an acceptable N-oxide;   (F) optionally further comprising converting the N-oxide form of the compound of formula I to its oxidized form. Conversion to a non-existent form;   (G) Optionally, further, the non-derivatized compound of the compound of formula I is pharmaceutically acceptable. To a prodrug derivative; and   (H) optionally further comprising converting a prodrug derivative of the compound of formula I Converting to body shape. Example:   The following examples are for illustrative purposes only and do not limit the invention. Those skilled in the art It will be understood that certain changes and modifications may be made within the scope of the present invention. .   Example 1.2-naphth-2-ylethylamine   Dissolution of 2-naphth-2-ylethanol (0.5 g, 2.9 mmol) in anhydrous DMF (5 ml) The solution was diluted with diphenylphosphoryl azide (0.74 ml, 3.42 mmol) and 1,8-diaza Along with bicyclo [5.4.0] untec-7-ene (0.74 ml, 3.14 mmol), We joined under the umbrella. The mixture is heated at 65 ° C. for 3 hours and then water and diethyl Ruether And divided between. The aqueous layer was separated and extracted with diethyl ether. So The combined organic layers were washed with 3N hydrochloric acid and then with saturated sodium bicarbonate. Clean and dry (MgSO 4_Four), Filtered and concentrated by rotary evaporation. Residue , THF (5 ml) and the solution was triphenylphosphine (1 g, 3.81). mmol), stirred at room temperature for 2 hours, diluted with water (0.100 ml), After stirring for an hour, dilute with concentrated hydrochloric acid (0.33 ml), precipitate, and add ethanol (5 ml). ), Dissolve the precipitate and slowly add diethyl ether To give a white precipitate. The white precipitate is isolated by filtration Washed with diethyl ether and dried under vacuum to give 2-naphtho- This gave 2-ylethylamine hydrochloride (0.447 g, 75% yield);   Working up as in Example 1, the following intermediate amine was prepared:   2-naphth-1-ylethylamine: yield = 56%,   3-microhexylpropylamine: yield = 40%,  3-phenyl-2-propenylamine: yield = 53%,   3-phenyl-2-propynylamine: yield = 62%, ;as well as   3,3-diphenylpropylamine: yield = 50%, Example 2.2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl ) -N- (4-phenylbutyl) -1H-benzimidazole-5-carboxa Midotrifluoroacetate (Compound 1)   (A) Ethyl cyanoacetate (8 ml, 75 mmol) in anhydrous benzene (100 ml) Was combined with absolute ethanol (6 ml, 105 mmol) under nitrogen. The mixture Is cooled to 10 ° C. (water / acetone) and bubbled with anhydrous hydrogen chloride gas for 20 minutes I let it go. The mixture was slowly warmed to room temperature, sealed, and stirred for about 18 hours. Was. The mixture is diluted with diethyl ether (400ml) and at room temperature for 5 hours And allowed to stand to give a crystalline solid. The solid is isolated by filtration and dried in anhydrous diethyl ether. Washed several times with tel and dried, ethyl as a colorless crystalline solid. Produced 3-ethoxy-3-iminopropionate (13.2 g, 90% yield);   (B) 3,4-diaminobenzoic acid (9.4 g, 62 mmol), ethyl 3-ethoxy- A mixture of 3-iminopropionate and glacial acetic acid (15 ml) was added under nitrogen for 30 minutes. Stirred at 0 ° C. Pour the mixture onto crushed ice (50 ml) and stir for 30 minutes Stirring yielded a dark yellow oil. The mixture was added with diethyl ether (25 ml) While stirring Stirring yielded a gray precipitate. The precipitate was isolated by filtration and diethyl ether And dried under vacuum to give 2-ethoxycarbonylmethyl 1H-benzimidazole-5-carboxylic acid was obtained (12.6 g, 83% yield);   (C) dinitrophenylmethanol (22 g, 111 mmol) in THF (450 ml), Triphenylphosphine (34.5 g, 131 mmol) and phthalimide (17.6 g, 119 mmol) and diethyl azodicarboxylate (20.7 ml, 131 mmol). While dropping, the mixture was stirred at −10 ° C. (ice / acetone) under nitrogen. The mixture is -10 Stir at 2 ° C. for 2 hours and then dilute with diethyl ether (900 ml), And stored at -20 ° C for about 18 hours to give a crystalline solid. The solid is separated by filtration, After washing, 2- (3,4-dinitrobenzyl) isoindole-1,3-di- On was obtained as an off-white crystalline solid (24.6 g, 67% yield);   (D) 2- (3,4-dinitrobenzyl) isoindo prepared in Example 1 1,3-dione (8 g, 24.4 mmol) and 10% palladium on carbon (300 mg) Is mixed with absolute ethanol (200 ml), anhydrous THF (100 ml) and glacial acetic acid (30 ml). Both were combined under a continuous stream of nitrogen. The mixture is stirred at room temperature under nitrogen for 15 hours. Stirred, filtered and concentrated on a rotary evaporator to a volume of about 30 ml. Its mixing The material was diluted with water (100 ml) and ammonium hydroxide was added and the orange A colored precipitate was obtained. The precipitate is isolated by filtration and washed several times with water, 2- (3,4-diaminobenzyl) iso Indole-1,3-dione was obtained (6 g, 91% yield);   (E) 2- (3,4-diaminobenzyl) isoindole-1,3-dione (2.0 g, 7.5 mmol) and 2-ethoxycarbonylmethyl-1H-benzimidazole -5-carboxylic acid (0.93 g, 3.75 mmol) For one hour at 185 ° C. The mixture was mixed with 1: 1 methylene chloride / ethanol The mixture was suspended in (20 ml) and stirred vigorously for 1 hour. Collect solids by filtration Wash with 1: 1 methylene chloride / ethanol (3 × 20 ml) and dry In short, 2- [5- (1,3-dioxo-1,3-dihydroisoindole-2) -Ylmethyl) -1H-benzimidazol-2-ylmethyl] -1H-benzo There was obtained imidazole-5-carboxylic acid (0.98 g, 29% yield);   (F) 2- [5- (1,3-dioxo-1,3-dihydroisoindole-2) -Ylmethyl) -1H-benzimidazol-2-ylmethyl] -1H-benzo Imidazole-5-carboxylic acid (0.05 g, 0.111 mmol) was added to anhydrous dimethylformate. Amide (0.5 ml) and the solution was diluted with 1-hydroxybenzotriazo Hydrate (0.017 g, 0.126 mmol), benzotriazol-1-yloxytriol Spirolidinophosphonium hexafluorophosphate (0.063 g, 0.121 mmol) And N-methylmorpholine (0.013 ml, 0.118 mmol) together with anhydrous N_TwoUnder the atmosphere And combined at room temperature. After 2 minutes, 4-phenylbutylamine (0.02ml, 0.127m ) And add The mixture was stirred at room temperature for 2 hours. Mix the mixture with 20% ethanol / acetic acid Ethyl solution (7 ml), 0.2N HCl (3.5 ml) and saturated NaCl aqueous solution (3.5 ml) Transferred to a liquid funnel. The aqueous phase was brought to 1 with a 20% ethanol / ethyl acetate solution (7 ml). Once extracted and combined organic phase was washed with 0.2N HC1 in saturated aqueous NaCl (3.5 ml). 1 (3.5 ml), followed by a saturated aqueous sodium hydrogen carbonate solution ( 7 ml) for a final wash. Next, the organic phase is dried over anhydrous sodium sulfate. Filtered, filtered and concentrated to dryness on a rotary evaporator to give 2- [5- (1,3-dioxane). Oxo-1,3-dihydroisoindol-2-ylmethyl) -1H-benzimi Dazol-2-ylmethyl] -N- (3-phenylpropyl) -1H-benzoy Midazole-5-carboxamide was obtained as a crude material (0.14 g).   (G) 2- [5- (1,3-dioxo-1,3-dihydroisoindole-2) -Ylmethyl) -1H-benzimidazol-2-ylmethyl] -N- (3-f Enylpropyl) -1H-benzimidazole-5-carboxamide (0.14 g, Was dissolved in absolute ethanol (0.5 ml) and the solution was dried with anhydrous hydrazide. (0.15 ml, 0.48 mmol). The mixture is_Two1 hour under reflux , Heated and then concentrated on a rotary evaporator. Residue under vacuum (0.15 torr) For 2 hours to remove excess hydrazine. The residue was treated with 3M HCl (0.5 ml) And the mixture was heated at 50 ° C. for 20 minutes. The reaction mixture Cooled to room temperature and stirred for another 20 minutes, causing a solid to precipitate. Filter the precipitate Isolated by filtration and washed with water (4 × 1.5 ml). Combine the filtrate, and 2 Washed with 0% ethanol / ethyl acetate solution (2 × 7 ml). Combined aqueous The phases were lyophilized to give the crude product as the hydrochloride. The crude material is inverted for separation Purification by phase HPLC gave 2- [5- (1, 3-dioxo-1,3-dihydroisoindol-2-ylmethyl) -1H-be [Nzoimidazol-2-ylmethyl] -N- (3-phenylpropyl) -1H- Benzimidazole-5-carboxamide (0.04 g, 0.07 mmol) was converted to a white solid. Obtained   Working up as in Example 2, the following compounds of the invention were prepared:   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -Naphth-1-ylmethyl-1H-benzimidazole-5-carboxamide ( Compound 2),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -Benzyl-1H-benzimidazole-5-carboxamide (Compound 3),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(3-phenylpropyl) -1H-benzimidazole-5-carboxamide (Compound 4),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(2-phenylethyl) -1H-benzimidazole-5-carboxamide ( Compound 5),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(3-aminomethyl) benzyl-1H-benzimidazole-5-carboxa Mid (compound 6),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(2-aminomethyl) -1-methyl-1H-benzimidazole-5-carbo Oxamide (compound 7),  2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(2-aminoethyl) -1H-benzimidazole-5-carboxamide Compound 8),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(4-aminobutyl) -1H-benzimidazole-5-carboxamide Compound 9),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(3-Aminopropyl) -1H-benzimidazole-5-carboxamide ( Compound 10),as well as   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -Cyclohexylmethyl-1H-benzimidazole-5-carboxamide Compound 11), Example 3.2- (5-aminomethyl-1H-benzimidazole-2 -Ylmethyl) -N- (3-aminopropyl) -1-methyl-1H-benzoimid Dazol-5-carboxamide (Compound 12)   (A) In a sealed tube, 3-nitro-4-chlorobenzoic acid (1.3 g, 6.4 5 mmol), a mixture of 10% methylamine and water (10 ml) is heated at 100 ° C. for 11 hours , Concentrated to 1 ml and then diluted with concentrated hydrochloric acid to give a yellow precipitate. Sinking The residue is isolated by filtration, washed with water and then with diethyl ether, and Drying gave 3-nitro-4-methylaminobenzoic acid (2.1 g, 86% yield). ;   (B) Ethyl alcohol (100 ml) was added to 3-nitro-4-methylaminobenzoic acid (2.09 g, 10.7 mmol) and 10% Pd / c (30 mg) N_TwoAdded under flow. The mixture was stirred under hydrogen for 16 hours, Millipore 0.22 μm Filtered through a type GV filter disc and concentrated on a rotary evaporator. The residue was dried under vacuum and 3-amino-4-methylaminobenzoic acid (1.1 g, 61% yield).   (C) Ethyl 3-ethoxy-3-i prepared as in Example 2 (a) Minopropionate was treated under conditions similar to those set forth in Example 2 (b) with 3-A Reacted with mino-4-methylaminobenzoic acid to give 2-ethoxycarbonylmethyl -1-Methyl-1H-benzimidazole-5-carboxylic acid was obtained (71% yield). ;   (D) 2- (3,4-diaminobenz prepared as in Example 2 (d) (Jill) isoindole-1,3-dione was prepared according to the conditions shown in Example 2 (e). Under the same conditions, 2-ethoxycarbonylmethyl-1-methyl-1H-benzimida After reacting with sol-5-carboxylic acid, 2- [5- (1,3-dioxo-1,3 -Dihydroisoindol-2-ylmethyl) -1H-benzimidazole-2 -Ylmethyl] -1-methyl-1H-benzimidazole-5-carboxylic acid (48% yield);   (E) 2- [5- (1,3-dioxo-1,3-dihydroisoindole-2) -Ylmethyl) -1H-benzimidazol-2-ylmethyl] -1-methyl- 1H-benzimidazole-5-carboxylic acid (0.05 g, 0.108 mmol), 1-H Droxybenzotriazole (0.016 g, 0.118 mmol), 1- (3-dimethylamido) Nopropyl) -3-ethylcarbodiimide hydrochloride (0.023 g, 0.12 mmol) and 1 The mono-BOC protected derivative of 2,3-diaminopropane was converted to methyl chloride at 0 ° C. (1 ml) and DMF (minimum enough to give a solution). The solution PH was adjusted to about 8 with N-methylmorpholine and the mixture was brought to room temperature. Warm up and then stirred for 20 hours. Transfer the mixture to a separatory funnel and add salt Diluted with methylene chloride, 0.1N HCl solution and then saturated NaHCO 3_ThreeWash with solution And dried over sodium sulfate, filtered, and concentrated. For separation of residue Purification by TLC (10% methanol / ethyl acetate) gave 2- [6- (1,3-dioxane). So-1,3-dihydroisoindol-2-ylmethyl) -1H-benzimida Zol-2-ylmethy 1] -methyl-N- (3-aminopropyl) -1H-benzimidazole- 5-carbaxamide was obtained (0.02 g, 28% yield);   (F) 2- [6- (1,3-dioxo-1,3-dihydroisoindole-2) -Ylmethyl) -1H-benzimidazol-2-ylmethyl] -1-methyl- N- (3-aminopropyl) -1H-benzimidazole-5-carboxamide Was deprotected under conditions analogous to those set forth in Example 2 (g), giving 2- (5-amino Nomethyl-1H-benzimidazol-2-ylmethyl) -N- (3-aminopropyl (Ropyl) -1-methyl-1H-benzimidazole-5-carboxamide was obtained. (20% yield);  The following compounds of the invention were prepared by working up as in Example 3. :   3- [2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) ) -N- (2-Naphth-1-ylethyl) -1H-benzimidazole-5-ca Luboxamide (compound 13),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(3,3-diphenylpropyl) -1H-benzimidazole-5-carboxy Samide (compound 14),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(2-Naphth-2-ylethyl-1H-benzimidazole-5-carboxa Mid (compound 15),   2- (1H-benzimidazol-2-ylmethyl) -N- [2 (1H-in Dol-3-yl) ethyl] -1H-benzimidazole-5-carboxamide (Compound 16),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -[2- (5-methoxy) indol-3-yl] -1H-benzimidazole -5-carboxamide (compound 17),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(2,3,4,5,6-pentahydroxyhexyl) -1H-benzimidazo Ole-5-carboxamide (compound 18),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(2-phenoxyethyl) -1H-benzimidazole-5-carboxamide (Compound 19),  2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(3-phenylprop-2-ynyl) -1H-benzimidazole-5-cal Boxamide (compound 20),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(E-3-phenylallyl) -1H-benzimidazole-5-carboxami (Compound 21),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(3-cyclohexylpropyl) -1H-benzimidazole-5-carboxy Samide (compound 22),  3- [2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) ) -N-oct-1-yl-1H-benzimidazole-5-carboxamide ( Compound 23),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -Methyl-N- (2-phenylethyl) -1H-benzimidazole-5-car Boxamide (compound 24), as well as   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(1-Methyl-3-phenylpropyl) -1H-benzimidazole-5-ca Luboxamide (compound 25), Example 4.C- {2- [5- (4-phenylbutoxy) -1H-benzimidazo -2-ylmethyl] -1H-benzimidazol-5-yl} methylamine (Compound 26)   (A) 4-phenyl-1-butanol (1 ml, 6.49 mmol) in THF (3 ml) In a 60% mineral oil dispersion with sodium hydride (0.26 g, 6.5 mmol) in anhydrous nitrogen We joined under the umbrella. The mixture is stirred vigorously for 5 minutes and 3,4-dinitrochloro Combine with benzene (1.3 g, 6.42 mmol) and then stir at room temperature for 10 hours did. The mixture was partitioned between diethyl ether and 3N hydrochloric acid. Aqueous layer Separated and extracted several times with diethyl ether. Dry the combined organic layers Dry (MgSO 4_Four), Filtered and concentrated on a rotary evaporator. Flush residue Purification by chromatography (9: 1 hexane / diethyl ether) , 4- (4-phenylbutoxy) -1,2-dinitrobenzene (1.16 g, 72% yield) Rate);   (B) Ethyl 3-ethoxy-3-imino prepared as in Example 2 (a) Propionate was prepared under conditions similar to those set forth in Example 2 (b) using 2- (3, 4-diaminobenzyl) isoindole-1,3-dione and reacted with ethyl 5- (1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl) -1H-ben Zoimidazol-2-yl acetate was obtained (71% yield);  (C) 4- (4-phenylbutoxy) -1,2-dinitrobenzene was prepared according to Example 3 ( Reduction under conditions similar to those shown in b), 4- (4-phenylbutoxy) Benzene-1,2-diamine was obtained (86% crude yield).   (D) 5- (4-phenylbutoxy) benzene-1,2-diamine (0.06 g, 0.234 mmol) and ethyl 5- (1,3-dioxo-1,3-dihydroisoin) Dol-2-ylmethyl) -1H-benzimidazol-2-yl acetate ( (0.1 g, 0.234 mmol) was heated at 185 ° C. under nitrogen for 1 hour. Its mixing The material was suspended in diethyl ether and stirred vigorously for 1 hour. Collect solids by filtration The residue was washed with diethyl ether and dried to give 2- {2- [5- (4 -Phenylbutoxy) -1H-benzimidazol-2-ylmethyl] -3H- Benzimidazol-5-ylmethyldiisoindole-1,3-dione was obtained. (0.1 g, 0.18 mmol).   (E) 2- {2- [5- (4-phenylbutoxy) -1H-benzimidazo) Ru-2-ylmethyl] -3H-benzimidazol-5-ylmethyldiisoin Dole-1,3-dione is protected under conditions similar to those set forth in Example 2 (g) And release C- {2- [5- (4-phenylbutoxy) -1H-benzimidazo Ru-2-ylmethyl] -1H-benzimidazol-5-yl} methylamine Fed (0.05 g, 55% yield); Example 5.2-phenylethyl 2- (5-aminomethyl-1H-benzimidazo Ru-2-ylmethyl) -1H-benzimidazole-5-carbamate trifur Oroacetate (Compound 27)   2- [5- (1,3-dioxo-) in phenetanol (0.160 ml, 1.34 mmol). 1,3-dihydroisoindol-2-ylmethyl) -1H-benzimidazo Ru-2-ylmethyl] -1H-benzimidazole-5-carboxylic acid (0.060 g, 0.133 mmol) at room temperature under nitrogen with diphenylphosphoryl azide (0.034 ml, 0 .158 mmol) and triethylamine (0.022 ml, 0.158 mmol). The mixture was stirred at 120 ° C. for 1 hour, cooled to room temperature and ethanol (0.5 m l) and hydrazine (0.020 ml, 0.637 mmol). 95 ℃ of the mixture For 45 minutes, cooled to room temperature and diluted with 3N hydrochloric acid (0.5 ml). That The mixture was stirred at 55 ° C. for 20 minutes and then filtered. 3N filtered solid And the combined filtrates are washed with ethyl acetate (15 ml). And lyophilized. The residue is purified by preparative reverse phase HPLC and the desired crude The product was fed (0.008 g, 11% yield); Example 6.2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -N- (2-naphthalen-1-ylethyl) -3-methyl-3H-benzimidida Sol-5-carbox Samide (compound 28)   (A) 2-nitro-1,4-phenylenediamine (21. 0 g, 137 mmol) and 4.0 M hydrogen chloride in dioxane (30.8 ml, 123 mmol) Is stirred at room temperature for 15 minutes, and then diethyl ether ( 1 l) was added and a precipitate formed. The precipitate was collected by filtration and additional diethyl Wash with ether and dry under vacuum to give 2-nitro-1,4-phenyl Nilenediamine hydrochloride (23.3 g, 100% yield) was obtained.   (B) 2-nitro-1,4-phenylenediamine hydrochloride (15.0 g, 79.1 mmol) ), A mixture of cyanamide (25.0 g, 595 mmol) and water (5 ml) was heated at 60 ° C. And stir for 1.5 h, cool to room temperature, and then add excess diethyl ether Was slowly added to obtain a precipitate. The precipitate is collected by filtration and additional diethyl Washed with toluene, dried under vacuum and N- (4-amino-3-nitro Phenyl) guanidine hydrochloride (18.0 g, 98% yield) was obtained;   (C) N- (4-amino-3-nitrophenyl) guanidine hydrochloride (12.0 g, 51.8 mmol), 10% palladium on carbon (1.0 g), tetrahydrofuran (100 ml) and And a mixture of methanol (100 ml) was hydrogenated at 1 atm, filtered and filtered under vacuum. And N- (3,4-diaminophenyl) guanidine hydrochloride as a dark solid Salt (10.3 g, 98% yield) was obtained;   (D) N- (3,4-diaminophenyl) guanidine hydrochloride (9.9 g, 49 mmol) ), Ethoxycarbonimidoylacetic acid ethyl ester hydrochloride (12.4 g, 59 mmol) ) And acetic acid (20 ml) in oil Heat in the bath at 110 ° C. and stir for 1.5 hours, cool to room temperature and vacuum Concentrated under. The residue was dissolved in ethanol (15 ml) and then ethyl acetate (10 ml) was added to the solution and the precipitate was suspended. Filter the suspension, and Excess ethyl ether was added to the filtrate to give a second precipitate. The precipitate is filtered Collected, washed with additional ethyl ether and dried under vacuum, As a white solid, ethyl 5-guanidino-1H-benzimidazole-2 -Yl acetate hydrochloride (14.1 g, 94% yield) was obtained;  (E) 4-nitro-3-methoxybenzoic acid (5.0 g, 25.4 mmol) and aqueous methyl Luamine (40%, 15 ml) in a sealed tube at 100 ° C. for 12 hours Heat in an oil bath, cool to room temperature, and then stir in 1M aqueous hydrochloric acid. Into an orange precipitate to give an orange precipitate. The precipitate is collected by filtration and Rinse and recrystallize from hot ethanol to give 3 as a bright red crystalline solid -Methylamino-4-nitrobenzoic acid was obtained (3.6 g, 73% yield);   (F) 3-methylamino-4-nitrobenzoic acid (13.0 g, 66.3 mmol), PyBO P (38.0 g, 73.0 mmol), hydroxybenztriazole hydrate (9.9 g, 73.0 mmol) mmol), dimethylformamide (100 ml) and N-methylmorpholine (18.3 ml). The mixture containing was mixed at room temperature for 15 minutes and then 2-naphthen-1-yl Ethylamine (13.8 g, 66.3 mmol) was added. Allow the mixture for an additional 30 minutes Stir and concentrate under vacuum. The residue was partitioned between ice and ethyl acetate, and The organic layer with water, 0.1 M aqueous hydrochloric acid, saturated aqueous Wash with sodium bicarbonate and then with saturated aqueous sodium chloride, dry Tight (magnesium sulfate), filtered, and concentrated in vacuo. Residue, eta Purified by recrystallization from phenol, 3-methylmethion as a light red crystalline solid. Ruamino-N- (2-naphthalen-1-yl-ethyl) -4-nitrobenzami (21.3 g, 92% yield);   (G) 3-methylamino-N- (2-naphth-1-ylethyl) -4-nitro Benzamide (21.3 g, 61 mmol), 10% palladium on carbon (1.0 g), tetra A mixture containing hydrofuran (100 ml) and methanol (100 ml) at 1 atmosphere pressure Hydrogenate, filter and concentrate under vacuum to afford 4-A as a colorless amorphous solid. Mino-3-methylamino-N- (2-naphth-1-ylethyl) -4-benzure Mido (18.4 g, 95% yield) was obtained;   (H) Ethyl 5-guanidino-1H-benzimidazol-2-yl acetate Hydrochloride (0.5 g, 1.7 mmol), 4-amino-3-methylamino-N- (2-naph To-1-ylethyl) -4-benzamide (0.5 g, 1.7 mmol) and dimethylform The mixture containing muamide (2 ml) was heated at 185 ° C. in an oil bath and nitrogen atmosphere. Stir for 3.5 h at ambient temperature, cool to room temperature, and stir in acetonitrile (150 ml). Poured to give a precipitate. The precipitate was added to additional acetonitrile and diethyl ether (150 ml), collected by filtration and dried under vacuum, off-white A solid was obtained. The solid was purified by reverse phase preparative HPLC to give 2- (5 -Guanidino-1H -Benzimidazol-2-ylmethyl) -N- (2-naphth-1-ylethyl) ) -3-Methyl-3H-benzimidazole-5-carboxamide was obtained (0.5 g). , 5.7%); LRMS (ESI): C₃₀H₂₈N₈Calculated value for O: 516.6; found (MH⁺) : 517.2.   Example 7.Ethyl 2- (4- {2- [1- (5-guanidino-1H-benzimidida) Zol-2-yl) ethyl] -1,4,6,7-tetrahydroimidazo [4,5 -C] pyridin-5-yl} -4-oxobutyl) benzoate (Compound 29)   (A) Ethyl 2-cyanopropionate (100 g, 0.2 g) in ethanol (65 ml) 9 mol) is cooled to 0 ° C. and then saturated with anhydrous hydrogen chloride gas. did. The mixture was warmed to room temperature, stirred for 24 hours, cooled to 0 ° C, and Saturated with elemental gas. The mixture was warmed to room temperature and stirred for another 24 hours. Ethyl ether: hexane (1: 1) was added to the mixture to give a precipitate. Settling The product was isolated by filtration and dried under vacuum to give ethyl 2- (N -Ethoxyamidino) propionate hydrochloride (119.6 g, 73% yield) was obtained:   (E) 3,4-diaminopyridine (51.7 g, 0.46 mmol), ethyl 2- (N- Ethoxyamidino) propionate hydrochloride (125 g, 0.69 mol) and glacial acetic acid (200 ml) Is heated at 85 ° C. and stirred for 18 hours, and then at 120 ° C. Heat and stir for an additional hour. The mixture is cooled to room temperature and under vacuum And concentrated. The residue was neutralized by addition of excess 5M aqueous ammonium hydroxide. And the mixture was extracted with ethyl acetate. Saturate the organic layer with saturated aqueous sodium bicarbonate And then saturated aqueous sodium chloride and dried (MgSO 4)._Four), Filtration And concentrate under vacuum, ethyl 1H-imidazo [4,5-c] pyridine-2-carboxylate (60.4 g, 58% Yield);   (C) Ethyl 1H-imidazo [4,5-c] pyridine-2- was added to a Parr hydrogenation apparatus. A mixture comprising the carboxylate (34.7 g, 158 mmol) is applied at 50 psi for 24 hours , Hydrogenated, filtered and concentrated in vacuo. Remove the oily residue with minimal In sodium chloride and anhydrous sodium chloride solution in dioxane (4M, 120 ml) , 475 mmol) was added to the solution. Add excess ethanol to the solution A precipitate was obtained. The precipitate was collected by filtration and dried under vacuum, ethyl 1,4,6,7-tetrahydro-1H-imidazo [4,5-c] pyridine-2- Carboxylate dihydrochloride was obtained (30.7 g, 66% yield);  (D) Ethyl 1,4,6,7-tetrahydro-1H-imidazo [4,5-c] Pyridine-2-carboxylate dihydrochloride (60.2 g, 0.20 mol), acetonitrile (500 ml) and a mixture containing diisopropylethylamine (100 ml, 0.60 mol). Cool to 0 ° C. and slowly add benzyl chloroformate (58 ml, 0.40 mol) While stirring. The mixture was slowly warmed to room temperature and continued for another 16 hours , Stirred and concentrated in vacuo. Dissolve the residue in ethyl ether (500 ml) and add The solution to 0.1 M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated aqueous salt. Washed with sodium chloride, dried over anhydrous sodium sulphate, filtered and filtered. And concentrate under vacuum to provide a colorless oil. Dissolve the residue in ethanol (320 ml) Understand To cool the solution to 0 ° C. and then ethanol, sodium ethoxide solution (2.6 M, 85 ml, 0.22 mol) was added slowly. The mixture at 0 ° C. for 1 hour, Stir and then a solution of hydrogen chloride in dioxane (4M, 50 ml) was added. The mixture was concentrated under vacuum and the residue was taken up in ethyl acetate (250 ml) and saturated Dissolved in aqueous thorium solution. Separate the organic layer and add saturated aqueous sodium chloride Wash more, dry over anhydrous sodium sulfate, filter, and concentrate under vacuum As a yellow amorphous material, 5-benzyl-2-ethyl-1,4,6,7-te Obtaining trahydroimidazo [4,5-c] pyridine-2,5-dicarboxylate (52 g, 72% yield);   (E) 4-chlorobutyryl chloride (12.6 g, 89.2 mmol), tert-butanol (25 ml), pyridine (6.9 g, 86.5 mmol) and 4-dimethylaminopyridine (1. (G, 8.2 mmol) at 50 ° C. for 12 hours under an atmosphere of anhydrous nitrogen. To give a white suspension. The suspension was partitioned between ethyl ether (250 ml) and water. And the organic layer is separated and 0.1 M aqueous hydrochloric acid, saturated aqueous sodium carbonate And washed repeatedly with saturated aqueous sodium chloride and over anhydrous magnesium sulfate. Dry, filter, and concentrate under vacuum to give a colorless oil. The oil Was distilled at 0.5 mmHg (51 ° C.) to give tert-butyl 4-chlorobutyrate as a colorless liquid. (11.27 g, 73% yield);   (F) Ethyl salicylate (3.14 g, 18.9 mmol), cesium carbonate (6.2 g, 18. 9 mmol), dimethylformamide (25 ml) and tert- A mixture containing butyl-4-chlorobutyrate (4.08 g, 22.8 mmol) was added at 70 ° C. Heated and stirred for 12 hours. The mixture was mixed with ethyl ether (100 ml) and water. And the organic layer separated, and additional water (3 ×) and saturated aqueous chloride Wash with sodium, dry over anhydrous magnesium sulfate, filter, and And concentrated in vacuo to give a colorless oil. The residue is purified with pure hexane: ethyl acetate Purified by flash chromatography on silica gel using 10: 1 Ethyl 2- (3-tert-butoxycarbonylpropoxy) as a colorless oil ) Benzoate was obtained (3.6 g, 62% yield):   (G) Ethyl 2- (3-tert-butoxycarbonylpropoxy) benzoate (3.60 g, 11.7 mmol) at room temperature for 1 hour and excess trifluoroacetic acid Processed. The solution is concentrated under vacuum and the oily residue is removed (10: 1) Hexanes: Flash silica gel with ethyl acetate to pure ethyl ether Purification by chromatography gave 4- (2-ethoxyca) as a colorless crystalline solid. (Rubonylphenoxy) butyric acid was obtained (2.81 g, 95% yield);   (H) benzyl 2-ethoxycarbonylmethyl-1,4,6,7-tetrahydride Loimidazo [4,5-c] pyridine-5-carboxylate (1.7 g, 4.8 mmol) , N- (3,4-diaminophenyl) guanidine hydrochloride (0.8 g, 4.0 mmol) and Heating the mixture containing dimethylformamide (2 ml) in an oil bath at 185 ° C. And nitrogen The mixture was stirred for 2.5 hours under a basic atmosphere. Cool the mixture to room temperature and stir Meanwhile, the mixture was poured into acetonitrile (150 ml) to obtain a precipitate. Add the precipitate to additional Wash with tonitrile and diethyl ether (150 ml), collect by filtration and And dried under vacuum to give an off-white solid. The solid was separated by reverse phase HPLC. Benzyl 2- [1- (5-guanidino-1H-benzene) as a white solid. Zoimidazol-2-yl) ethyl] -1,4,6,7-tetrahydroimidazo [4,5-c] pyridine-2-carboxylate was obtained (1.0 g, 55% yield); LRM S (ESI): C_{twenty four}H₂₆N₈O_TwoCalculated for: 458.5; found (MH^-): 459.2.   (I) benzyl 2- [1- (5-guanidino-1H-benzimidazole-2) -Yl) ethyl] -1,4,6,7-tetrahydroimidazole [4,5-c] Pyridine-5-carboxylate (1.0 g, 2.2 mmol), 10% palladium on carbon (0.5g), a mixture containing tetrahydrofuran (50ml) and methanol (50ml) Is hydrogenated at 1 atmosphere, filtered and concentrated in vacuo to give N- {2- [1 -(4,5,6,7-tetrahydroimidazo [4,5-c] pyridin-2-yl ) Ethyl] -1H-benzimidazol-5-yl) -guanidine was obtained (0.69). g, 97% yield); LRMS (ESI): C₁₆H₂₀N₈Calculated for: 324.4; found (M H⁺): 325.2.   (J) 4- (2-ethoxycarbonylphenoxy) butyric acid (155 mg, 0.61 mmol) ), PyBOP (360 mg, 0.69 mmol), hydroxybenztriazole hydrate (87 mg , 0.64 mmol), N-methylmorpholine (0.16 ml, 0.92 mmol) and dimethylformol The mixture containing muamide (2.5 ml) was stirred at room temperature for 10 minutes and then N-Ｎ 2- [1- (4,5,6,7-tetrahydroimidazo [4,5-c] pyridine- 2-yl) ethyl] -3H-benzimidazol-5-yl @ D Anidi (203 mg, 0.63 mmol) was added. The mixture was stirred at room temperature for 3 hours. And concentrated in vacuo. Dissolve the residue in 5% aqueous acetonitrile, and The product was purified by preparative reverse phase HPLC. Next, freeze the combined pure fractions After drying, ethyl 2- (4- {2- [1- (5-guanidino-1H-benzoy) Midazol-2-yl) ethyl] -1,4,6,7-tetrahydroimidazo [4 , 5-c] pyridin-5-yl {-4-oxobutyl) benzoate; LR MS (Bioion); C₂₉H₃₄N₈O_FourCalcd for: 558.6; found: 559.3.   Example 8.2- [1- (5-hydroxy-1H-benzimidazol-2-yl) Ethyl] -N- [2- (2-methoxyphenoxy) ethyl] -3-meta-3H- Benzimidazole-5-carboxamide (Compound 30)   (A) tert-butyl 2-hydroxyethylcarba in dichloromethane (60 ml) The solution of mate (25 ml, 161.6 mmol) was cooled to 0 ° C and the first diisopro- Stir while adding pyrethylamine (33.8 ml, 193.9 mmol) and add To this was added mesyl chloride (13.7 ml, 177.8 mmol) dropwise. Warm the mixture to 23 ° C Stir for 18 hours, pour into dichloromethane (200 ml), and add aqueous hydrochloric acid (3M, (3 × 25 ml) and saturated aqueous sodium bicarbonate (2 × 25 ml). Organic The layers were separated and dried (MgSO_Four), And concentrated in vacuo to a ter t-Butyl 2-methylsulfonyloxyethyl carbamate was obtained (37.39 g, 97 % (Yield); MS (PB-PCI) C₈H₁₇NO_FiveS m / e; calculated value 239.08; measured value 240 (MH⁺ ).   (B) Lithium bromide (136 g, 1.56 mol) was added to tetrahydrofuran (600 ml) in 0%. Dissolved at ° C. The mixture was warmed to 23 ° C. and then tert-butyl 2-methyl Rusulfonyloxyethyl carbamate (37.39 g, 156 mmol) was added dropwise. The mixture was stirred at 23 ° C. for 18 hours and then And concentrated under vacuum. Dissolve the residue in hexane and separate the organic layer with water and brine. And then dried (Na_TwoSO_Four) And concentrated in vacuo to give a brown oil This gave tert-butyl 2-bromoethyl carbamate (33.48 g, 96% yield). ; MS (PB-PCI) C₇H₁₄BrNO_Twom / e; calculated 224.10; found 225 (MH⁺).   (C) 2-methoxyphenol (9.8 ml, 89.3 mmol), dimethylformamide (100 ml) and potassium carbonate (61.5 g, 445 mmol) were mixed with tert-butyl. Stir at 23 ° C. while adding 2-bromoethyl carbamate (20 g, 89.3 mmol). Stirred. The mixture was stirred for 24 hours and then ethyl ether: hexane (1: 1, 400 ml) and washed with water (5 × 50 ml). Add aqueous layer Extracted with chill ether: hexane (1: 1, 3 × 40 ml) and combined Dry the organic layer (Na_TwoSO_Four) And concentrated in vacuo to a yellow oil, tert-Butyl 2- (2-methoxyphenoxy) ethyl carbamate was obtained (23.22 g, 97% yield); MS (PB-PCI) C₁₄H_{twenty one}NO_Fourm / e; calculated 267.32; measured 268 (M H⁺).   (D) tert-butyl 2- (2-methoxyphenoxy) ethyl carbamate (23 .8 g, 89 mmol) were cooled to 0 ° C. and trifluoroacetic acid: dichloromethane (1: 1, 40 ml) was added dropwise while stirring. Warm the mixture to 23 ° C Stirred for 2 hours and concentrated in vacuo. The residue was taken up in dichloromethane (100 ml ) And the solution is washed with saturated aqueous sodium bicarbonate (3 x 20 ml) and water Wash with aqueous sodium hydroxide (10%, 3 × 20 ml) and dry (Na_TwoSO_Four), Filter and concentrate under vacuum to give 2- (2-methoxyphenyl) as a pale yellow solid. (Noxy) ethylamine was obtained (13 g, 88 % Yield); MS (PB-PCI) C₉H₁₃NO_Twom / e; calculated 167.21; measured 168 (MH^-).   (E) 3-methoxy-4-nitrobenzoic acid (15.42 g, 78.2 mmol) and titanium chloride A heterogeneous mixture containing onyl (70 ml, 391 mmol) was heated under reflux for 1 hour. Excess thionyl chloride is removed by distillation and the residue is concentrated in vacuo to give a pale yellow 3-methoxy-4-nitrobenzoyl chloride was obtained as a colored solid (16.8 g). , 99% yield); MS (PB-PCI) C₉H₆ClNO_Four  m / e; calculated value 215.59; measured value 216 (MH⁺).   (F) 2- (2-methoxyphenoxy) ethylamine (10 g, 59.9 mmol), Diisopropylethylamine (13.9 ml, 81.6 mmol) and dichloromethane (80 ml ) Was cooled to 0 ° C., and then 3-dichloromethane (50 ml) was added. A solution of methoxy-4-nitrobenzoyl chloride (11.76 g, 54.4 mmol) was added dropwise. did. The mixture was warmed to 23 ° C. for 2 hours and poured into aqueous hydrochloric acid (3M, 20 ml). Cool more quickly, wash with water (3 × 20 ml), dry (Na_TwoSO_Four), And Concentrate in vacuo to afford N- [2- (2-methoxyphenoxy) as an off-white solid. C) Ethyl] -3-methoxy-4-nitrobenzamide was obtained (14 g, 74% yield). ); MS (PB-PCI) C₁₇H₁₈N_TwoO₆  m / e; calculated 346.34; found 347 (MH⁺).   (G) N- [2- (2-methoxyphenoxy) ethyl in a sealed tube ] -3-methoxy-4-nitrobenzamide (4.0 g, 11.6 mmol), aqueous methyl Heat a mixture of amine (40%, 10 ml) and DMSO (2 ml) at 110 ° C. for 4 hours and cool And then poured into water (25 ml). Treating the solution with 3M aqueous hydrochloric acid, An orange solid was obtained. The solid was isolated by filtration and N- [2- (2-meth Xyphenoxy) ethyl] -3-methylamino-4-nitroben MS (PB-PCI) C was obtained (3.56 g, 89% yield).₁₇H₁₉N_ThreeO_Five  m / e; Calculated 345.35; Found 346 (MH⁺).   (H) N- [2- (2-methoxyphenoxy) ethyl] -3-methylamino- 4-nitrobenzamide (3.56 g, 10.3 mmol), suspended in methanol (100 ml) Containing palladium on carbon (10%, 0.5g) and tetrahydrofuran (50ml) The mixture was stirred under a hydrogen atmosphere at ambient pressure for 2.5 hours. Filter the mixture And the solution was concentrated under vacuum to give 4-amino-N- [2- ( 2-methoxyphenoxy) ethyl] -3-methylaminobenzamide was obtained (3. MS (PB-PCI) C₁₇H_{twenty one}N_ThreeO_ThreeM / e; calculated 315.37; Measured 316 (MH⁺).   (I) In a Parr apparatus, 4-amino-3-nitrophenol (5.0 g, 32.4 m Mol), on carbon, a mixture of palladium (10%, 1.0 g) and methanol (50 ml) Was hydrogenated at 50 psi for 3 hours, filtered through celite and concentrated in vacuo. To give 3,4-diaminophenol as a dark solid (4.02 g, 91% yield) ); MS (PB-PCI) C₆H₈N_TwoO m / e; calculated 124.16; found 125 (MH⁺).   (J) 3,4-diaminophenol (3.661 g, 29.5 ml), ethyl 2- (N-E Toxiamidino) propionate (7.423 g, 38.4 mmol) and ethanol (30 ml )) Was heated under reflux for 6 hours and concentrated in vacuo. Vinegar residue Dissolve in ethyl acetate (200 ml) and add the solution to saturated aqueous sodium bicarbonate (3. × 20 ml) and brine (1 × 20 ml) and dried (MgSO 4)._Four), And Concentrate in vacuo to afford ethyl 2- (5-hydroxy-1H-benzo) as a dark solid. (Imidazol-2-yl) propionate was obtained (6.3 g, 91% yield). Solid Likagel flash chromatography (100% ethyl acetate); MS (PB-PCI) C₁₂H₁₄N_TwoO_Threem / e; Calculated value 234.28; Actual value 235 (MH⁺).   (K) Ethyl 2- (5-hydroxy-1H-benzimidazol-2-yl) Propionate (148 mg, 0.63 mmol), 4-amino-N- [2- (2-methoxy [Enoxy) ethyl] -3-methylaminobenzamide (200 mg, 0.63 mmol) and 1 , 3-Dimethyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidone (0.5 ml) of the mixture was stirred at room temperature until homogeneous, vented under vacuum, and N_TwoConcentrated by heating at 170 ° C. for 2 hours under flowing water. Cool the residue to room temperature And rinsed with excess ethyl ether. 50% of amorphous material obtained Take up in aqueous acetonitrile and preparative reverse phase HPLC (2-50% CH 2)_ThreeCN / H_TwoO) Purified and obtained 2- [1- (5-hydroxy-1H-benzo) as a light pink solid. Imidazol-2-yl) ethyl] -N- [2- (2-methoxyphenoxy) e Tyl] -3-methyl-3H-benzimidazole-5-carboxamide was obtained ( 40 mg, 13% yield); MS (Biolon) C₂₇H₂₇N_FiveO_Fourm / e; calculated value 485.59; measured value 486.5 (MH⁺).   The following compounds of the invention were prepared by working up as in Example 8: (2- {2- [1- (5-fluoro-1H-benzimidazol-2-yl) d) Tyl] -3-methyl-3H-benzimidazol-5-ylcarbonylamino} Ethoxy) benzoate (compound 31), MS (Biolon) C_{twenty four}H₂₆N_FiveO_FourF m / e Calculated value 515.54; measured value 516 (MH⁺);   2- (2- {2- [1- (5-fluoro-1H-benzimidazol-2-i) L) ethyl] -3-methyl-3H-benzimidazol-5-ylcarbonyla Minodiethoxy) benzoic acid (compound 32) MS (Biolon) C₂₇H_{twenty four}N_FiveO_FourF m / e calculated value 501.52; measured value 502.1 (MH^-);   Ethyl 2- (2- {2- [1- (5-hydroxy-1H-benzimidazole) -2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcar Bonylaminodiethoxy) benzoate (compound 33), MS (Biolon) C₂₉H_{twenty five}N_Five O_Threem / e calculated 527.58; found 528.1 (MH⁺);   2- (2- {2- [1- (5-hydroxy-1H-benzimidazole-2- Yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcarbonyl Aminodiethoxy) benzoic acid (compound 34), MS (Biolon) C₂₇H_{twenty five}N_FiveO_Fivem / e Calculated 499.53; Found 500.1 (MH⁺);   N-ethyl-2- [1- (5-hydroxy-1H-benzimidazole-2- Yl) ethyl] -3-methyl-3H-benzimidazole-5-carboxamide (Compound 35), MS (Biolon) C₂₀H_{twenty one}N_FiveO_Twom / e calc. 363.42; found 364.1 ( MH^-);   2- [1- (5-hydroxy-1H-benzimidazol-2-yl) ethyl ] -N- (2-methoxyethyl) -3-methyl-3H-benzimidazole-5 -Carboxamide (compound 36), MS (Biolon) C_{twenty one}H_{twenty three}N_FiveO_Threem / e calculated 393. 45; actual value 394.1 (MH⁺);   Butyl 2- (2- {2- [1- (5-hydroxy-1H-benzimidazole) -2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcar Bonylaminodiethoxy) benzoate (compound 37), MS (Biolon) C₃₁H₃₃N_Five O_Fivem / e calculated 555.64; found 555.7 (MH^-);   3- {2- [1- (5-guanidino-1H-benzimidazole -2-yl) ethyl] -6 [2- (2-methoxyphenoxy) ethylcarbamoy Ru] benzimidazol-1-yl} propane-1-sulfonic acid (compound 38), MS (LCMS) C₃₀H₃₅N₈O₆Sm / e calculated 635.72; found 635.4 (MH⁺);   N- [2- (2-ethoxyphenoxy) ethyl] -2- [1- (5-hydroxy C-1H-benzimidazol-2-yl) ethyl-3-methyl-3H-benzo Imidazole-5-carboxamide (compound 39), MS (Biolon) C₂₆H₂₉N_FiveO_Four m / e calculated 499.58; found 500.4 (MH⁺);   2- [1- (5-hydroxy-1H-benzimidazol-2-yl) ethyl ] -N- [2- (2-isopropoxyphenoxy) ethyl] -3-methyl-3H -Benzimidazole-5-carboxamide (compound 40), MS (Biolon) C₂₉H₃₁ N_FiveO_Fourm / e calc. 513.61; found 514.5 (MH⁺);   2- [1- (5-hydroxy-1H-benzimidazol-2-yl) ethyl ] -3-Methyl-N- [2- (2-propoxyphenoxy) ethyl] -3H- Nzoimidazole-5-carboxamide (Compound 41), MS (Biolon) C₂₉H₃₁N_Five O_Fourm / e calc. 513.61; found 514.2 (MH^-);   Propyl 2- (2- {2- [1- (5-hydroxy-1H-benzimidazo) Ru-2-yl) ethyl] -3-methyl-3H-benzimidazol-5-dolphin Rubonylaminodiethoxy) benzoate (compound 42), MS (ESI) C₃₀H₃₁N_FiveO_Five m / e calculated 541.61; found 542.2 (MH⁺);   Isobutyl 2- (2- {2- [1- (5-hydroxy-1H-benzimidazo) 2-yl) ethyl] -3-methyl-3H-benzimidazol-5-yl Carbonylaminodiethoxy) benzoe (Compound 43), MS (Biolon) C₃₁H₃₃N_FiveO_Fivem / e calculated 555.64; found 55 6.3 (MH⁺);   Ethyl 4- {2- [1- (5-hydroxy-1H-benzimidazole-2- Yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcarbonyl Aminobutyrate (compound 44), MS (Biolon) C_{twenty four}H₂₇N_FiveO_Fourm / e calculated 449. 51; actual value 449.9 (MH⁺);   4- {2- [1- (5-hydroxy-1H-benzimidazol-2-yl) Ethyl] -3-methyl-3H-benzimidazol-5-ylcarbonylamino ｝ Butyric acid (compound 45), MS (Biolon) C_{twenty two}H_{twenty three}N_FiveO_Fourm / e calculated value 421.46; measured value 422.1 (MH⁺);   Isopropyl 2- (2- {2- [1- (5-hydroxy-1H-benzoimida) Zol-2-yl) ethyl] -3-methyl-3H-benzimidazol-5-i Lecarbonylaminodiethoxy) benzoate (compound 46), MS (ESI) C₃₀H₃₁ N_FiveO_Fivem / e calculated 541.61; found 542.2 (MH⁺);   N- {2- [2- (1-ethylpropoxy) phenoxy] ethyl} -2- [1 -(5-hydroxy-1H-benzimidazol-2-yl) ethyl] -3-me Tyl-3H-benzimidazole-5-carboxamide (compound 47), MS (BioI on) C₃₁H₃₅N_FiveO_Fourm / e calculated 541.65; found 542.2 (MH⁺);   Ethyl-2- (2- {2- [1- (5-fluoro-1H-benzimidazole) -2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcar Bonylaminodiethoxy) benzoate (Compound 48), MS (BioIon) C₂₉H₂₈N_Five O_FourFm / e calculated 529.57; found 529.5 (MH⁺);   2-methoxyethyl 2- (2- {2- [1- (5-hydroxy- 1H-benzimidazol-2-yl) ethyl] -3-methyl-3H-benzoi Midazol-5-ylcarbonylaminodiethoxy) benzoate (Compound 49) , MS (BioIon) C₃₀H₃₁N_FiveO₆m / e calculated 557.61; found 58.2 (MH⁺);   N- (3-methoxypropyl) -2- [1- (5-hydroxy-1H-benzo) Imidazol-2-yl) ethyl] -3-methyl-3H-benzimidazole- 5-carboxamide (compound 50), MS (BioIon) C_{twenty two}H_{twenty five}N_FiveO_Threem / e calculated value 407 .47; actual value 408.0 (MH⁺);   2- [1- (5-hydroxy-1H-benzimidazol-2-yl) ethyl ] -N- [2- (2-methoxymethylphenoxy) ethyl] -3-methyl-3H -Benzimidazole-5-carboxamide (compound 51), MS (BioIon) C₂₈H₂₉ N_FiveO_Fourm / e calculated: 499.57; found 499.8 (MH^-);   N- [2- (2-ethoxymethylphenoxy) ethyl] -2- [1- (5-h Droxy-1H-benzimidazol-2-yl) ethyl] -3-methyl-3H -Benzimidazole-5-carboxamide (compound 52), MS (BioIon) C₂₉H₃₁ N_FiveO_Fourm / e calculated 513.60; found 514.1 (MH⁺);   Ethyl 2- (2- {2- [1- (6-fluoro-5-hydroxy-1H-benzene) Zoimidazol-2-yl) ethyl] -3-methyl-3H-benzimidazole -5-ylcarbonylaminodiethoxy) benzoate (compound 53), MS (ESI) C₂₉H₂₈N_FiveO_ThreeF m / e calculated 545.57; found 546.3 (MH⁺);   Ethyl 2- (2- {2- [1- (5-hydroxy-1H-benzimidazole) -2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcar Bonylaminodiethoxy) cyclohexa Carboxyate (compound 54), MS (BioIon) C₂₉H₃₅N_FiveO_Fivem / e calculated value 53 3.63; actual value 534 (MH⁺);   2- [1- (5-hydroxy-1H-benzimidazol-2-yl) ethyl ] -3-Methyl-N- [2- (2-propoxymethylphenoxy) ethyl] -3 H-benzimidazole-5-carboxamide (compound 55), MS (BioIon) C₃₆ H₃₃N_FiveO_Fourm / e calc. 527.62; found 527.6 (MH⁺);   2- [1- (5-hydroxy-1H-benzimidazol-2-yl) ethyl ] -N- [2- (2-isopropoxymethylphenoxy) ethyl] -3-methyl -3H-benzimidazole-5-carboxamide (compound 56), MS (BioIon) C₃₀H₃₃N_FiveO_Fourm / e calc. 527.62; found 527.9 (MH⁺);   2- [1- (5-hydroxy-1H-benzimidazol-2-yl) ethyl ] -N- (2- [2- (2-methoxyethoxymethyl) phenoxy] ethyl}- 3-methyl-3H-benzimidazole-5-carboxamide (compound 57), MS (BioIon) C₃₀H₃₃N_FiveO_Fivem / e calculated 543.42; found 543.4 (MH⁺);   2- [1- (1H-benzimidazol-2-yl) ethyl] -N- [2- ( 2-methoxymethylphenoxy) ethyl] -3-methyl-3H-benzimidazo 5-Carboxamide (Compound 58), MS (BioIon) C₂₈H₂₉N_FiveO_Threem / e meter Calculated value 483.57; Observed value 484 (MH⁺);   N- [2- (2-ethoxymethylphenoxy) ethyl] -2- [1- (1H- Benzimidazol-2-yl) ethyl] -3-methyl-3H-benzimidazo 5-Carboxamide (Compound 59), MS (BioIon) C₂₉H₃₁N_FiveO_Threem / e meter Calculated 497.6; Found 498.3 (MH⁺);   2- [1- (1H-benzimidazol-2-yl) ethyl] -3-methyl- N- [2- (2-propoxymethylphenoxy) ethyl] -3H-benzimida Sol-5-carboxamide (Compound 60), MS (BioIon) C₃₀H₃₃N_FiveO_Threem / e Calc. 511.62; found 511.5 (MH⁺);   2- [1- (1H-benzimidazol-2-yl) ethyl] -N- [2- ( 2-isopropoxymethylphenoxy) ethyl] -3-methyl-3H-benzoi Midazole-5-carboxamide (Compound 61), MS (BioIon) C₃₀H₃₅N_FiveO_Threem / E calculated 511.62; found 511.6 (MH^-);   2- [1- (1H-benzimidazol-2-yl) ethyl] -N- {2- [ 2- (2-methoxyethoxymethyl) phenoxy] ethyl} -3-methyl-3H -Benzimidazole-5-carboxamide (compound 62), MS (BioIon) C₃₀H₃₅ N_FiveO_Fourm / e calc. 527.62; found 527.7 (MH⁺);   2- [1- (5-hydroxy-1H-benzimidazol-2-yl) ethyl ] -3-Methyl-N- [2- (2-morpholin-4-ylphenoxy) ethyl] -3H-benzimidazole-5-carboxamide (compound 63), MS (BioIon) C₃₀H₃₂N₆O_Fourm / e calculated 540.73; found 541.8 (MH⁺);   N- (2-phenylsulfonylethyl) -2- [1- (5-hydroxy-1H -Benzimidazol-2-yl) ethyl] -3-methyl-3H-benzimidida Zole-5-carboxamide (Compound 64), MS (BioIon) C₂₆H_{twenty five}N_FiveO_FourS m / E calculated 503.59; measured 504.2 (MH⁺);   2- (2- {2- [1- (6-fluoro-5-hydroxy-1H-benzoimid) Dazol-2-yl) ethyl] -3-methyl-3H- Benzimidazol-5-ylcarbonylaminodiethoxy] benzoic acid (compound 65), MS (ESI) C₂₇H_{twenty four}N_ThreeO_FiveF m / e calculated 517.52; found 518.2 (MH⁺);   Ethyl 2-hydroxy-5- {2- [1- (5-hydroxy-1H-benzoi) Midazol-2-yl) ethyl] -3-methyl-3H-benzimidazole-5 -Ylcarbonylamino dibenzoate (compound 66), MS (BioIon) C₂₇H_{twenty five}N_Five O_Fivem / e calculated 499.52; found 500.2 (MH⁺);   2- [1- (5-fluoro-1H-benzimidazol-2-yl) ethyl] -3-Methyl-N- [2- (2-morpholin-4-ylphenoxy) ethyl]- 3H-benzimidazole-5-carboxamide (compound 67), MS (BioIon) C₃₀ H₃₁N₆O_ThreeFm / e calculated 542.62; found 543.4 (MH⁺);   N- (2-phenylsulfonylethyl) -2- [1- (5-fluoro-1H- Benzimidazol-2-yl) ethyl] -3-methyl-3H-benzimidazo 5-Carboxamide (Compound 68), MS (BioIon) C₂₆H_{twenty four}N_FiveO_ThreeFS m / E calculated 505.58; measured 506.5 (MH⁺);   Ethyl 2-(-2- {2- [1- (4,6-difluoro-5-hydroxy-1 H-benzimidazol-2-yl) ethyl {-3-methyl-3H-benzimi Dazol-5-ylcarbonylaminodiethoxy) benzoate (compound 69), MS (BioIon) C_{twenty five}H₂₇N_FiveO_FiveF_Twom / e calculated 563.52; found 563.4 (MH⁺);   2- (2- {2- [1- (4,6-difluoro-5-hydroxy-1H-ben) Zoimidazol-2-yl) ethyl] -3-methyl-3H-benzimidazole -5-ylcarbonylaminodiethoxy) benzoic acid (compound 70), MS (BioIon) C₂₇H_{twenty three}N_FiveO_FiveF_Twom / e calculated 536.51; found 563 (MH⁺);   Ethyl 2-(-2- {2- [1- (4,6-difluoro-5-imidazole- 1-yl-1H-benzimidazol-2-yl) ethyl] -3-methyl-3H -Benzimidazol-5-ylcarbonylaminodiethoxy) benzoate ( Compound 71), MS (BioIon) C₃₂H₂₉N₇O_FourF_Twom / e calculated 613.62; found 614.3 (MH⁺);   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -3-Methyl-N- {2- [2- (3-methyl- [1,2,4] oxadiazo Yl-5-yl) phenoxy] ethyl} -3H-benzimidazole-5-car Boxamide (Compound 72), MS (BioIon) C₃₀H₃₀N_TenO_Threem / e calculated 578.63; actual Measurement 579.4 (MH⁺);as well as   2- [1- (5-imidazol-1-yl-1H-benzimidazole-2- Yl) ethyl] -3-methyl-N- {2- [2- (3-methyl [1,2,4] o Xiadiazol-5-yl) phenoxy] ethyl} -3H-benzimidazole -5-carboxamide (compound 73), MS (BioIon) C₃₂H₂₉N_FiveO_Threem / e calculated value 587.64; actual value 588.2 (MH⁺).   Example 9.2- [2- (2- {1- [5- (1-iminoethyl) -4,5,6,7 -Tetrahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl -3-methyl-3H-benzimidazol-5-ylcarbonylamino) ethoxy B] Benzoic acid (compound 74)   (A) A solution of 3,4-diaminopyridine (51.7 g, 0.46 mol) in acetic acid (400 ml) Was heated to 85 ° C., and then diethylmethyl-1-iminomalonate (125 g, 0.60 mol) was added in three equal portions over 6 hours. Bring the mixture to 85 ° C for 1 2 hours and at 120 ° C Heated for 1 hour, cooled and concentrated under reduced pressure. Cool the residue to 0 ° C And neutralized with 5N ammonium hydroxide. Wash the aqueous layer several times with ethyl acetate And the combined extracts are continuously extracted with sodium bicarbonate and salt. Wash with sodium chloride and dry (Na_TwoSO_Four), Filter and concentrate under reduced pressure And ethyl 2- (1H-imidazo [4,5-c] pyridine as an amber solid. -2-yl) propionate was obtained (60.4 g, 58%).  (B) Ethyl 2- (1H-imidazo [4,5- c) A solution of pyridin-2-yl) propionate (60.4 g, 0.28 mol) was oxidized. Hydrogenated in the presence of platinum (IV) (58) at 50 psi for 2 hours. The mixture is filtered, Then, it was concentrated under reduced pressure. The residue was cooled to 0 ° C. and 4M HCl / dioxane , Suspended in ether, isolated by filtration and dried. Fresh A solution of the residue (15-20 g each) in trifluoroacetic acid (50 ml each) Hydrogenated at 50 psi for 24 hours in the presence of platinum (IV) oxide (5 g). Filter the mixture And concentrated under reduced pressure. The residue is dissolved in toluene / ethanol (about 1: 1) And azeotropically dried with a mixture of 4M HCl / dioxane, suspended in ether, Isolated by filtration, dried under vacuum and ethyl 2- (4,5,6,7-tetra Hydroimidazo [4,5-c] pyridin-2-yl) propionate dihydrochloride Obtained (61.80 g, 75% yield);   (C) Ethyl 2- (4,5,6,7-tetrahydride in acetonitrile (400 ml) Loimidazo [4,5-c] pyridin-2-yl) propionate dihydrochloride (60.2 g, 0.20 mol) was cooled to 0 ° C. under nitrogen and N, N-diisopropylamine was added. (35 ml, 0.20 mol), further cooled to about -5 ° C (ice / acetone), And then alternately for 30 minutes, benzyl chloroformate (58 ml, 0.41 mol) and Treated with N, N'-diisopropylethylamine (70 ml, 0.40 mol). So The mixture was cooled at -5 ° C for 1 hour and warmed to 20 ° C, and after 16 hours, Concentrated under. The residue is suspended in ether, and the suspension is Washed with sodium hydrogen, sodium chloride, 0.1M hydrochloric acid and sodium chloride And dried (Na_TwoSO_Four), Filtered and concentrated under reduced pressure. Ethano residue (320 ml), and the solution is cooled to −5 ° C. under nitrogen and then , Sodium ethoxide (21 wt%, 85 ml, 0.22 mol) at a reaction temperature of 0 ° C or less Was added dropwise over 1 hour. The mixture is left for 1 hour at -5 ° C. Cooled, adjusted to neutral with 50 ml of 4M hydrochloric acid and concentrated under reduced pressure. Residue Was dissolved in ethyl acetate, and the solution was treated with sodium bicarbonate and sodium chloride. , Filtered and concentrated under reduced pressure. Remove the residue with silica gel Purified by chromatography (hexane / ethyl acetate) to give a pale yellow oil Benzyl 2- (1-ethoxycarbonylethyl) -1,4,6,7-tetra Hydromidazo [4,5-c] pyridine-5-carboxylate was obtained (52 g, 72 %yield);   (D) benzyl 2- (1-ethoxycarbonylethyl) -1,4,6,7-te Trahydroimidazo [4,5-c] pyridine-5-carboxylate (6.37 g, 0 .018 mol), 4-amino-3- (N-methylamino) benzoic acid (2.70 g, 0.016 mol ) And DMPU (20 ml) were degassed under vacuum and 185 g under nitrogen for 4 hours. C., cooled and combined with a tube volume of benzene. Next, ether Was added to the mixture to obtain a precipitate. The precipitate is isolated by filtration and immediately vacuum Dry underneath and further purified by reprecipitation from hot ethanol / water did. The precipitate was isolated by filtration and dried, giving 2- [1- (5-be Benzyloxycarbonyl-4,5,6,7-tetrahydro-1H-imidazo [4 , 5-c] pyridin-2-yl) ethyl] -3-methyl-3H-benzimidazo Toluene-5-carboxylic acid was obtained (4.73 g, 58% yield);  (E) 2- [1- (5-benzyloxycarbonyl-4,5,6,7-tetra Hydro-1H-imidazo [4,5-c] pyridin-2-yl) ethyl] -3-me Tyl-3H-benzimidazole-5-carboxylic acid (0.75 g, 1.6 mmol), DMF (6.5 ml), methyl 2- (2-aminoethoxy) benzoate (0.38 g, 1.6 m Of HOBT (0.22 g, 1.6 mmol) was cooled to -40 ° C under nitrogen and the EDC ( 0.32 g, 1.6 mmol) and N, N-diisopropylethylamine (0.29 ml, 1.6 mmol) And after 15 minutes additional N, N-diisopropylethylamine (0.29 ml), warm to 20 ° C, And stirred for 16 hours. The mixture was then cooled to -40 ° C and additional EDC (0.0 80 g) and N, N-diisopropylethylamine (0.050 ml). Stirred at 15 ° C. for 15 minutes and at 20 ° C. for 2 hours and concentrated by short path distillation. Residue Is separated between chloroform and sodium bicarbonate, and the organic liquid is separated into sodium chloride Wash with lithium, 0.5M potassium sulfate and sodium chloride and dry (N a_TwoSO_Four), Filtered and concentrated under reduced pressure. The residue is purified by silica gel chromatography. Fee (CHCl_Three/ MeOH / AcOH: 95/5/1) to give a glassy brown foam As benzyl 2- (1- {6- [2- (2-methoxycarbonylphenoxy) ) Ethylcarbamoyl] -1-methyl-1H-benzimidazol-2-yl Ethyl) -1,4,6,7-tetrahydroimidazo [4,5-c] pyridine-5 Obtaining the carboxylate (0.69 g, 66%);  (F) Benzyl 2- (1- {6- [2- (2- (2-)-) in THF (2 ml) and water (2 ml). Methoxycarbonylphenoxy) ethylcarbamoyl] -1-methyl-1H-beta Nzonimidazol-2-yldiethyl] -1,4,6,7-tetrahydroimida Solution of zo [4,5-c] pyridine-5-carboxylate (0.69 g, 1.1 mmol) Was cooled to 0 ° C. under nitrogen and treated with 2N lithium hydroxide (1.1 ml, 2.2 mmol). And warmed to 20 ° C. and stirred for 8 hours. Next, the mixture Cool to 0 ° C, treat with 2N lithium hydroxide (1.1 ml), warm to 20 ° C, Stir for hours, cool to 0 ° C., adjust to pH 7 with 1 M hydrochloric acid, and Concentrated. The residue is carefully washed with cold sodium chloride and water, and And dried under vacuum to give 5-benzyloxycarbonyl as a glassy residue. -2- (2- {3-methyl-2- [1- (4,5,6,7-tetrahydro-1H -Imidazo [4,5-c] pyridin-2-yl) ethyl] -3H-benzimidida Sol-5-ylcarbonylaminodiethoxy) benzoic acid was obtained (0.50 g, 83%). );  (G) 5-benzyloxycarbonyl-2- (2- {3-) in glacial acetic acid (2 ml) Methyl-2- [1- (4,5,6,7-tetrahydro-1H-imidazo [4,5 -C] pyridin-2-yl) ethyl] -3H-benzimidazol-5-dolphin Rubonylaminodiethoxy) benzoic acid (0.561 g, 0.90 mmol) And heated to 10 ° C. under nitrogen and with a solution of hydrogen bromide in acetic acid (2 ml of a 30% solution) Treated and warmed to 20 ° C., after 1 hour, concentrated with a stream of nitrogen. Small amount of residue Dissolve in ethanol and add the solution dropwise to stirring ether to give a light brown precipitate. I got The precipitate was isolated by filtration and dried, giving 2- (2- {3- Methyl-2- [4,5,6,7-tetrahydro-1H-imidazo [4,5-c] Pyridin-2-yl) ethyl] -3H-benzimidazol-5-ylcarboni (Ruaminodiethoxy) benzoic acid hydrobromide was obtained (0.651 g);   (H) In DMF (1.5 ml), 2- (2- {3-methyl-2- [4,5,6,7-te Trahydro-1H-imidazo [4,5-c] pyridin-2-yl) ethyl] -3 H-benzimidazol-5-ylcarbonylaminodiethoxy) benzoic acid The salt (0.3 g, 0.46 mmol) was cooled to 0 ° C. under nitrogen and ethyl acetylimidate (0.1 2 g, 0.22 mmol) and N, N-diisopropylethylamine (0.25 ml, 1.4 mmol) ), Cool at 0 ° C for 30 minutes, and then warm to 20 ° C and 20 hours And stirred. The mixture is then cooled to 0 ° C. and additional ethyl acetylimidate (0.06 g) and N, N-diisopropylethylamine (0.16 ml), Warmed to 20 ° C. and stirred for 2 hours. The mixture was cooled to 0 ° C and additional ethyl acetate was added. Treated with cetimidate (0.03 g), warmed to 20 ° C. and stirred for 2 hours. Next, the mixture was added dropwise to stirred ether to obtain a precipitate. Remove the precipitate and the solvent Isolated by canting and dried under vacuum. Ethano residue RP-HPLC: 50% MeCN / H_TwoO (20 mM H (Cl) over 50 minutes. The fractions were lyophilized, and 2- [2- (2 -{1- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H- Imidazo [4,5-c] pyridin-2-yl] ethyl {-3-methyl-3H-be Nzoimidazol-5-ylcarbonylamino) eth Xy] benzoic acid was obtained (0.145 g, 52%); Example 10.Ethyl 2- (2- {2- [1- (4,6,7-trifluoro-1H- N, N-Imidazol-2-yl) ethyl] -3-methyl-3H-benzimidazo Ru-5-carbonylaminodiethoxy) benzoate (compound 75)   (A) In dioxane (aldrich, 0.5 M, 7.5 mmol), 2,3,4,6-tetra A solution of fluoronitrobenzene (0.6 g, 3.1 mmol) and ammonia was added at room temperature for 3 hours. Stirred for hours to obtain a fine white precipitate. Dilute the mixture with an equal volume of water , The white precipitate dissolved and yellow crystals were obtained. Isolate and collect the crystals, and After drying, 2,3,5-trifluoro-6-nitroani Phosphorus (307 mg, 5 pb) was obtained; m.p. p. 66 ° C;   (B) 2,3,5-trifluoro-6-nitroaniline (3 00 mg, 1.56 mmol) and 10% palladium on carbon at atmospheric pressure overnight. Hydrogenate, filter under nitrogen and concentrate, as a purple crystalline solid, 1,2 -Diamino-3,4,6-trifluorobenzene (219 mg, 87% yield) was obtained; MSM +162.7, +41. +82 (+ ACN, + ACN). (C₆H_FiveF_ThreeN_TwoCalculated for: 16 2.11).   (C) 1,2-diamino-3,4,6-trifluorobenzene (1.92 g, 11.8 mmol), ethyl 2-ethoxycarboximidoyl propionate (3.1 g, 14.7 mmol) and anhydrous alcohol (6 ml), the reaction was allowed to proceed further. Heat at reflux until no further progress is indicated by TLC indicating no further progress , NH_FourFiltered from Cl and concentrated. Chromatography of the residue on silica Purification by treatment (hexane: methylene chloride: ethyl acetate; 5: 5: 1), crystals Ethyl 2- (4,6,7-trifluoro-1H-benzimidazo -2-yl) propionate was obtained (1.37 g, 42%);   (D) ethyl 2- (4,6,7-trifluoro-1H-benzimidazole- 2-yl) propionate (988 mg, 3.63 mmol) and ethyl 2- [2- (4-A Mino-3-methylaminobenzoylamino) ethoxy] benzoate (1.3 g, 3. 63 mmol) and put under vacuum for 4 hours and then further DMPU ( 4 ml). The mixture is removed under high vacuum to remove residual gas Stir in the solution overnight until evacuated and apply to 195 ° C under a stream of nitrogen for 4 hours. Heated, cooled to room temperature, and partitioned between ethyl acetate and water. Separate the organic layer, And washed with brine, dried over sodium sulfate and concentrated . The residue is purified by chromatography on silica gel (100% hexa Gradient from 100 to ethyl acetate) and further from MeOH / THF / water Was purified by crystallization of ethyl 2- (2-) as a white crystalline solid. {2- [1- (4,6,7-trifluoro-1H-benzimidazol-2-i Ru) ethyl] -3-methyl-3H-benzimidazole-5-carbonylamino (Ethoxy) benzoate was obtained (1.0 g, 49%); The following compounds of the invention were prepared as in Example 10:   Ethyl 2- (2- {2- [1- (5,6-difluoro-1H-benzimidazo) 2-yl) ethyl] -3-methyl-3H-benzimidazol-5-yl Carbonylaminodiethoxy) benzoate (compound 76), MS (BioIon) C₂₉H_{Two 7} N_FiveO_FourF_Twom / e calculated 547.56; found 548.1 (MH⁺);   Ethyl 2- (2- {2- [1- (4,6-difluoro-1H-benzimidazo) 2-yl) ethyl] -3-methyl-3H-benzimidazol-5-yl Carbonylaminodiethoxy) benzoate (Compound 77, MS (LCMS) C₂₉H₂₇F_Two N_FiveO_Fourm / e calculated 547.46; found 548.3 (MH⁺);   Ethyl 2- (2- {2- [1- (4,5,6-trifluoro-1H-benzoi) Midazol-2-yl) ethyl] -3-methyl-3H-benzimidazole-5 -Ylcarbonylaminodiethoxy) benzoate (compound 78), MS (LCMS) C₂₉ H₂₆F_ThreeN_FiveO_Fourm / e calculated 565.55; found 566.2 (MH⁺);as well as   Ethyl 2- {2- [3-methyl-2- (4,6,7-trifluoro-1H- (Nazoimidazol-2-ylmethyl) -3H-benzimidazol-5-dolphin Rubonylamino] ethoxydibenzoate (Compound 79), MS (BioIon) C₂₈H_{twenty four}F_ThreeN_FiveO_Fourm / e calculated 551.52; found 5 51.2.   Example 11.2- (2- {2- [1- (4,6,7-trifluoro-1H-benzoi) Midazol-2-yl) ethyl] -3-methyl-3H-benzimidazole-5 -Ylcarbonylaminodiethoxy) benzoic acid (compound 80)   Ethyl 2- (2- {2- [1- (4.6,7-trifluoro-1H-benzoi) Midazol-2-yl) ethyl] -3-methyl-3H-benzimidazole-5 -Carbonylaminodiethoxy) benzoate (118 mg, 0.21 mmol), methanol (4 ml) and 2N sodium hydroxide (2.1 ml) were stirred at room temperature for 4 hours. Stir, neutralize with 2N hydrochloric acid (2.1 ml), and add ethyl acetate and saturated ammonium chloride. Aum and divided between. The aqueous layer was separated and extracted with ethyl acetate (× 3) Was. Wash the combined organic layers with brine and dry over sodium sulfate. And concentrated to a white solid. The residue was washed with warm ethanol (10 ml) and 4M aqueous chloride. And dioxane solution. The solution was diluted with ethyl ether and precipitated. I got something. The precipitate was isolated and dried to give 2- (2- ｛) as a white solid. 2- [1- (4,6,7-trifluoro-1H-benzimidazol-2-yl ) Ethyl] -3-methyl-3H-benzimidazol-5-ylcarbonylamido Nodethoxy) benzoic acid was obtained; MS (LCMS) C₂₇H_{twenty two}F_ThreeN_FiveO_Fourm / e; calculated value 5 37.50; found 538.4 (MH⁺).   The following compounds of the invention were prepared as in Example 11:   2- (2- {2- [1- (5,6-difluoro-1H-benzimidazole- 2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcarbo Nilaminodiethoxy) benzoic acid (compound Product 81), MS (LCMS) C₂₇H_{twenty three}N_FiveO_FourF_Twom / e calc. 519.51; found 520.2 (MH⁺) ;   2- (2- {2- [1- (4,6-difluoro-1H-benzimidazole- 2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcarbo Nilaminodiethoxy) benzoic acid (Compound 82), MS (LCMS) C₂₇H_{twenty five}F_TwoN_FiveO_Four m / e calc. 519.51; found 520.2 (MH⁺);as well as   2- (2- {2- [1- (4,5,6-trifluoro-1H-benzimidazo) -2-yl) ethyl] -3-methyl-3H-benzimidazole-5-cal Bonylaminodiethoxy) benzoic acid (Compound 83), MS (BioIon) C₂₇H_{twenty two}F_ThreeN_Five O_Fourm / e calculated 537.5; found 537.7 (MH⁺).   Example 12.Ethyl 2- (2- {2- [1- (1-isobutyryl-5-methoxycal) Bonyloxy-1H-benzimidazol-2-yl) ethyl] -3-methyl- 3H-benzimidazol-5-ylcarbonylaminodiethoxy) benzoate G (compound 84)   Ethyl 2- (2- {2- [1- (5-hydroxy-1H-benzimidazole) -2-yl) ethyl] -3-methyl-3H-benzimidazole-5-carboni Ruaminodiethoxy) benzoate (0.50 g, 0.95 mmol), dimethylforma Amide (5 ml), cesium carbonate (0.93 g, 2.85 mmol) and isobutyric anhydride (0.17 g) ml, 1.05 mmol) is stirred for 2 hours and then taken up in dichloromethane (50 ml). Diluted and passed through a celite pad. The solvent is removed under vacuum and the residue Was dissolved in dichloromethane (5 ml). The solution is diluted with diisopropylethylamine. (0.47 ml, 2.7 mmol) and methyl chloroformate (0.1 ml, 1.3 mmol) Union, and the mixture Was stirred for 1 hour. The solvent was removed under vacuum and the residue was eluted as eluent. Purify by silica gel chromatography using ethanol and dichloromethane. And ethyl 2- (2- {2- [1- (1-isobutyi) as a colorless amorphous solid. 5-methoxycarbonyloxy-1H-benzimidazol-2-yl) d Tyl] -3-methyl-3H-benzimidazol-5-ylcarbonylamino} Ethoxy) benzoate was obtained (0.20 g, 32% yield); MS (BioIon) C₃₅H₃₇N_Five O₈m / e; calculated 655.72; found 656.1 (MH⁺).   The following pull-drugs of the invention were prepared as in Example 12: (1- {6- [2- (2-ethoxycarbonylphenoxy) ethylcarbamoyl) ] -1-Methyl-1H-benzimidazol-2-yl) ethyl] -5-hydro Xybenzimidazole-1-carboxylate (compound 85), MS (ESI) C₃₁H_{Three 1} N_FiveO₇m / e calculated 585.62; found 586.2 (MH⁺);   Ethyl 2- (1- {6- [2- (2-ethoxycarbonylphenoxy) ethyl] Carbamoyl] -1-methyl-1H-benzimidazol-2-yl) ethyl] -5-methoxycarbonyloxypenzoimidazole-1-carboxylate ( Compound 86), MS (ESI) C₃₃H₃₃N_FiveO₇m / e calculated 643.66; found 644.2 (MH⁺);   Ethyl 2- (2- {2- [1- (5-hydroxy-1-isobutyryl-1H- Benzimidazol-2-yl) ethyl] -3-methyl-3H-benzimidazo Yl-5-ylcarbonylaminodiethoxy) benzoate (compound 87), MS (E SI) C₃₃H₃₅N_FiveO₆m / e calculated 599.78; found 598.2 (MH⁺);   Ethyl 2- (2- {2- [1- (1-benzoyl-5-hydroxy-1H-beta) Nzoimidazol-2-yl) ethyl] -3-methyl -3H-benzimidazol-5-ylcarbonylaminodiethoxy) benzoe (Compound 88), MS (ESI) C₃₆H_{twenty three}N_FiveO₆m / e calculated 631.69; found 632.3 (M H⁺);   Ethyl 2- (2- {2- [1- (1-dimethylcarbamoyl-5-hydroxy) -1H-benzimidazol-2-yl) ethyl] -3-methyl-3H-benzo Imidazol-5-ylcarbonylaminodiethoxy) benzoate (Compound 89 ), MS (ESI) C₃₂H₃₄N₆O₆m / e calculated 598.66; found 599.3 (MH⁺);   Ethyl 2- (2- {2- [1- (1-acetoxymethyl-5-hydroxy-1) H-benzimidazol-2-yl) ethyl] -3-methyl-3H-benzimi Dazol-5-ylcarbonylaminodiethoxy) benzoate (compound 90), MS (BioIon) C₃₂H₃₃N_ThreeO₇m / e calculated 599.65; found 600.7 (MH^-);   Ethyl 2- [2- (2- {1- [1- (2,2-dimethylpropionyloxy) Methyl) -5-hydroxy-1H-benzimidazol-2-yl] ethyl}- 3-methyl-3H-benzimidazol-5-ylcarbonylamino) ethoxy Benzoate (compound 91), MS (ESI) C₃₅H₃₉N_FiveO₇m / e calculated 641.74; actual Measurement 642.3 (MH⁺);   Ethyl 2- (2- {2- [1- (1-isobutyryl-5-methoxycarbonyl) Oxy-1H-benzimidazol-2-yl) ethyl] -3-methyl-3H- Benzimidazol-5-ylcarbonylaminodiethoxy) benzoate Compound 92), MS (BioIon) C₃₅H₃₇N_FiveO₈m / e calculated 655.52; found 656.1 (MH⁺) ;   Ethyl 5-ethoxycarbonyloxy-2- (1- {6- [2- (2-ethoxy Cicarbonylphenoxy) ethylcarbonyl] -1-methyl-1H-benzoimid Dazol-2-yldiethyl) benzoi Midazole-1-carboxylate (compound 93), MS (ESI) C₃₅H₃₇N_FiveO₉m / e Calculated 671.72; Found 672.4 (MH⁺);   Isopropyl 2- (1- {6- [2- (2-ethoxycarbonylphenoxy) Ethylcarbamoyl] -1-methyl-1H-benzimidazol-2-yl Tyl) -5-isopropoxycarbonyloxy-benzimidazole-1-cal Boxylate (Compound 94), MS (ESI) C₃₇H₄₁N_FiveO₉m / e calculated 699.79; Value 700.4 (MH⁺);as well as   Ethyl 2- (2- {2- [1- (1-acetyl-5-hydroxy-1H-benzene) Zoimidazol-2-yl) ethyl] -3-methyl-3H-benzimidazole -5-ylcarbonylaminodiethoxy) benzoate (compound 95), MS (ESI) C₃₁H₃₁N_FiveO₆m / e calculated 569.62; found 570.1 (MH^-).   In accordance with the methods described herein or known to those skilled in the art, The following additional compounds of the invention were prepared:   C- [2- (5 aminomethyl-1H-benzimidazol-2-ylmethyl) -3H-benzimidazol-5-yl] methylamine (compound 96);   C- [2- (1H-naphtho [2,3-d] imidazol-2-ylmethyl)- [1H-benzimidazol-5-yl] methylamine (compound 97), MS (BioIon ) C₂₀H₁₇N_Fivem / e calculated 327.4; found 328.1 (MH⁺);   C- [2- (5-methyl-1H-benzimidazol-2-ylmethyl) -1 H-benzimidazol-5-yl] methylamine (Compound 98), MS (BioIon) C₁₇H₁₇N_Fivem / e calculated 291.4; found 292.3 (MH⁺);   2- (5-aminomethyl-1H-benzimidazol-2-yl Methyl) -1H-benzimidazole-5-carboxylic acid (Compound 99);   3- [2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) ) -1H-Benzimidazol-5-ylcarbonylamino] propionic acid Compound 100).   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -N -(2-Naphth-1-ylethyl) -1H-benzimidazole-5-carboxy Samide (compound 101),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -3 -Methyl-N- (2-naphth-1-ylethyl) -3H-benzimidazole- 5-carboxamide (compound 102),  2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -3 -Methyl-N- (2-naphth-1-ylethyl) -3H-benzimidazole- 4-carboxamide (compound 103),   (S) -2- [2- (5-aminomethyl-1H-benzimidazol-2-i Methyl) -1H-benzimidazol-5-ylcarbonylamino] -3-i Ndol-3-ylpropionic acid (compound 104),   (R) -2- [2- (5-aminomethyl-1H-benzimidazol-2-i Methyl) -1H-benzimidazol-5-ylcarbonylamino] -3-i Ndol-3-ylpropionic acid (compound 105),  2- (1H-benzimidazol-2-ylmethyl) -N- (2-naphth-1 -Ylethyl) -1H-benzimidazole-5-carboxamide (Compound 106) ,   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -3 -Methyl-N- (4-aminobutyl) -3H-benzimidazole-4-carbo Oxamide (Compound 107), MS (BioIon) C₃₂H₂₇N₇O₁m / e calculated value 405.4; measured value 406.5 (MH⁺);   2- [1- (5-aminomethyl-1H-benzimidazol-2-yl) ethyl 3-Methyl-N- (2-naphth-1-ylethyl) -3H-benzimida Sol-5-carboxamide (compound 108), MS (BioIon) C₃₁H₃₀N₆O₁m / e Calculated value 502.6; measured value 503.3 (MH^-);   2- (1H-imidazo [4,5-c] pyridin-2-ylmethyl) -3-methyl Ru-N- (2-naphth-1-ylethyl) -3H-benzimidazole-5-ca Luboxamide (Compound 109), MS (BioIon) C₂₈H_{twenty four}N₆O₁m / e calculated 460.5; Measurement 461.3 (MH⁺);   2- (5-aminomethyl-1H-benzimidazol-2-ylcarbonyl) -3-Methyl-N- (2-naphth-1-ylethyl) -3H-benzimidazo Ru-5-carboxamide (Compound 110), MS (BioIon) C₃₀H₂₆N₆O_Twom / e calculation Value 502.6; measured value 503.6 (MH⁺);   2- (5-carbamoyl-1H-benzimidazol-2-ylmethyl) -N -(2-Naphth-1-ylethyl) -1H-benzimidazole-5-carboxy Samide (compound 111),   2- (5-aminomethyl-4,5,6,7-tetrahydro-1H-benzoimid Dazol-2-ylmethyl) -3-methyl-N- (2-naphth-1-ylethyl ) -3H-Benzimidazole-5-carboxamide (Compound 112),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -3 -Methyl-N- (3-phenylpropyl) -3H-benzimidazole-5-ca Luboxamide (compound 113),   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -3 -Methyl-N- (2-phenoxyethyl) -3H-benzimidazole-5-ca Luboxamide (Compound 114),  2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- (2-na Fut-1-ylethyl) -3H-benzimidazole-5-carboxamide Compound 115),   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylcarbonyl] -3-methyl-N- (2 -Naphth-1-ylethyl) -3H-benzimidazole-5-carboxamide (Compound 116),   2- (5-iminomethyl-4,5,6,7-tetrahydro-1H-imidazo [ 4,5-c] pyridin-2-ylmethyl] -3-methyl-N- (2-naphth-1 -Ylethyl) -3H-benzimidazole-5-carboxamide (Compound 117) ,  2- (5-aminomethyl-4,5,6,7-tetrahydro-1H-benzoimid Dazol-2-ylcarbonyl) -3-methyl-N- (2-naphth-1-ylue Tyl) -3H-benzimidazole-5-carboxamide (compound 118),   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- (2-f Enoxyethyl) -3H-benzimidazole-5-carboxamide (Compound 119 ),   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- (2- Nzo [1,3] dioxol-4-ylethyl) -3H-benzimidazole- 5-carboxamide (Compound 120),  2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- (benzo Imidazol-1-ylethyl) -3H-benzimidazole-5-carboxa Mid (Compound 121),   N- [2- (5-hydroxy-1H-indol-2-yl) ethyl] -2- [5- (1-Iminoethyl) -4,5,6,7-tet Lahydro-1H-imidazo [4,5-c] pyridin-2-ylmethyl] -3-me Tyl-3H-benzimidazole-5-carboxamide (Compound 122),   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- [2- ( 2-chlorophenoxy) ethyl] -3H-benzimidazole-5-carboxa Mid (Compound 123), MS (BioIon) C₂₆H₂₈H₇O_TwoCl m / e calculated value 506.0; measured Value 506.3 (MH⁺);   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- [2- ( 3-chlorophenoxy) ethyl] -3H-benzimidazole-S-carboxica Mid (Compound 124), MS (BioIon) C₂₆H₂₈N₇O_TwoCl m / e calculated value 506.0; measured Value 506.7 (MH⁺);   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- (2-na Fut-1-ylethyl) -3H-benzimidazole-5-carboxamide Compound 125),   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- (2-h Droxy-2-naphth-1-ylethyl) -3H-benzimidazole-5-ca Luboxamide (Compound 126),   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- [2- ( 2-hydroxynaphth-1-yl) ethyl] -3H-benzimidazole-5 Carboxamide (compound 127),  2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- [2- ( 4-hydroxynaphthal-1-yl) ethyl] -3H-benzimidazole-5 Carboxamide (compound 128),   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- [2- ( 2-methoxyphenoxy) ethyl] -3H-benzimidazole-5-carboxy Samide (compound 129),   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N-naphtho- 2-ylmethyl-3H-benzimidazole-5-carboxamide (Compound 130) ,   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- (3-py (Lid-4-ylpropyl) -3H-benzimidazole-5-carboxamide ( Compound 131),   2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- (2,3-dihydroxy) propyl-N- (2-naphth-1-ylethyl) -3 H-benzimidazole-5-carboxamide (Compound 132), MS (BioIon) C₃₂ H₃₂N₈O_Threem / e calculated 576.6; found 577.5 (MH⁺);   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- [2- ( 4-methoxyphenoxy) ethyl] -3H-benzimidazole-5-carboxy Samide (compound 133),  2- (5-guanidino-1H-benzimidazol-2-ylcarbonyl)- 3- (2,3-dihydroxy) propyl-N- (2-naphth-1-ylethyl) -3H-benzimidazole-5-carboxamide (compound 134), MS (BioIon) C₃₂H₃₀N₇O_Fourm / e calculated 590.6; found 590.7 (MH⁺);   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- [2- ( 1,2,3,4-tetrahydronaphth-1-yl) ethyl] -3H-benzoimid Dazole-5-carboxamide (Compound 135),   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- [2- ( 3-methoxyphenoxy) ethyl] -3H-benzimidazole-5-carboxy Samide (compound 136),  2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -N- (3-Phenylpropyl-1H-benzimidazole-5-carboxamide Compound 137),   2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- (3-hydroxy) propyl-N- (2-naphth-1 -Ylethyl) -3H-benzimidazole-5-carboxamide (Compound 138) , 2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- ( 2,3-dihydroxy) propyl-N- [2- (2-methoxy) phenoxyethyl L] -3H-benzimidazole-5-carboxamide (compound 139), MS (BioIo n) C₂₉H₃₂N₈O_Fivem / e calculated 572.72; found 573.3 (MH⁺);  2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -3- (2,3-dihydroxypropyl) -N- (2-naphth-1-ylethyl ) -3H-benzimidazole-5-carboxamide (Compound 140), MS (BioIo n) C₃₃H₃₄N₈O_Three, M / e calculated 590.7; found 591.3 (MH⁺);   2- (5-guanidino-1H-benzimidazol-2-ylcarbonyl)- 3- (2,3-dihydroxypropyl) -N- [2- (2-methoxyphenoxy ) Ethyl] -3H-benzimidazole-5-carboxamide (Compound 141), MS (BioIon) C₂₉H₃₀N₈O₆ m / e calculated 586.6; found 587.5 (MH⁺);   2- [5- (1-Iminoethyl) aminomethyl-1H-benzimidazole- 2-ylmethyl] -3- (2,3-dihydroxy) propyl-N- [2- (2- Methoxy) phenoxyethyl] -3H-benzimidazole-5-carboxami (Compound 142),  Methyl 2- {2- [2- (5-guanidino-1H-benzimidazole-2- Ylmethyl) -3-methyl-3H-benzimidazol-5-ylcarbonyla Mino] ethoxydibenzoate (Compound 143), MS (BioIon) C₂₈H₂₈N₈O₁m / e calculated 54.56; found 541.4 (MH⁺);   2-{-2- [2- (5-guanidino-1H-benzimidazol-2-yl Methyl) -3-methyl-3H-benzimidazol-5-ylcarbonylamino Ethoxy benzoic acid (compound 144);   Methyl 3- {2- [2- (5-guanidino-1H-benzimidazole-2 -Ylmethyl) -3-methyl-3H-benzimidazo Yl-5-ylcarbonylamino] ethoxy} benzoate (compound 145), MS (B ioIon) C₂₈H₂₈N₆O_Fourm / e calculated 540.5; found 541.4 (MH⁺);   2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- Methyl-N- [2- (2,6-dimethoxy) phenoxyethyl] -3H-benzo Imidazole-5-carboxamide (compound 146),   2- (5-guanidinomethyl-1H-benzimidazol-2-ylmethyl) -3- (2,3-dihydroxy) propyl-N- [2- (2-methoxyphenoxy) C) ethyl] -3H-benzimidazole-5-carboxamide (compound 147),   2- (5-iminomethylaminomethyl-1H-benzimidazol-2-yl Methyl) -3- (2,3-dihydroxy) propyl-N- [2- (2-methoxy ) Phenoxyethyl] -3H-benzimidazole-5-carboxamide (compound 148),   2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- Methyl-N- (2-hydroxy-2-quinol-4-ylethyl) -3H-ben Zoimidazole-5-carboxamide (compound 149),  2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- Methyl-N- [2- (3-methyl-2,4-dioxoquinazolin-1-yl) e Tyl] -3H-benzimidazole-5-carboxamide (Compound 150), MS (Bio Ion) C₂₉H₂₈N_TenO_Threem / e calculated 564.6; found 565.5 (MH⁺);   Methyl 2- {2- [2- (5-guanidino-1H-benzimidazole-2- Ylcarbonyl) -3-methyl-3H-benzimidazol-5-ylcarboni [Amino] ethoxy} benzoate (Compound 151), MS (BioIon) C₂₈H₂₆N₈O_Five m / e calculated 554.5; found 554.8 (MH⁺);   2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- (2-hydroxy) ethyl-N- (2-naphth-1- Ylethyl) -3H-benzimidazole-5-carboxamide (Compound 152),   2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- Methyl-N- [2- (3-oxo-2,3-dihydrobenzo [1,4] oxadi N-4-yl) ethyl] -3H-benzimidazole-5-carboxamide Compound 153);   2- (5-guanidino-1H-benzimidazol-2-ylcarbonyl)- 3- (2-hydroxyethyl) -N- (2-naphth-2-ylethyl) -3H- Benzimidazole-5-carboxamide (compound 154),   2- (5-guanidino-1H-benzimidazol-2-ylcarbonyl)- 3-methyl-N- (2-naphth-1-ylethyl) -3H-benzimidazole -5-carboxamide (compound 155),   2- (5-guanidino-1H-benzimidazol-2-ylcarbonyl)- 3- (3-hydroxypropyl) -N- (2-naphth-1-ylethyl) -3H -Benzimidazole-5-carboxamide (compound 156);   2- (5-Imidazol-1-yl-1H-benzimidazol-2-ylmeth Tyl) -3-methyl-N- (2-naphth-1-yl Tyl) -3H-benzimidazole-5-carboxamide (Compound 157);   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -3-Methyl-N- (2-naphth-1-ylethyl) -3H-benzimidazo 5-Carboxamide (Compound 158), MS (BioIon) C₃₁H₃₀N₈O₁m / e meter Calculated 530.6; found 531.1 (MH⁺);   2- [1- (5-imidazol-1-yl-1H-benzimidazole-2- Yl) ethyl] -3-methyl-N- (2-naphth-1-ylethyl) -3H- Nzoimidazole-5-carboxamide (Compound 159), MS (BioIon) C₃₃H₂₉N₇ O₁m / e calculated 539.6; found 540.1 (MH⁺);   2- {1- [5- (2-aminoimidazol-1-yl) -1H-benzimi Dazol-2-yl] ethyl} -3-methyl-N- (2-naphth-1-ylethyl ) -3H-benzimidazole-5-carboxamide (Compound 160), MS (BioIo n) C₃₃H₃₀N₈O₁m / e calculated 554.7; found 555.2 (MH⁺);   1- (5-guanidino-1H-benzimidazol-2-yl) -3-hydro Xy-1-methyl-N- (2-naphth-1-ylethyl) -3,4-dihydro-1 H-2-oxa-4a, 9-diasafluorene-6-carboxamide (compound 161 );   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -3- (4-Hydroxybutyl) -N- (2-naphth-1-ylethyl) -3 H-benzimidazole-5-carboxamide (compound 162), MS (BioIon) C₃₄ H₃₆N₈O_Twom / e calculated 588.7; found 589.3 (MH⁺);   3- {2- [1- (5-guanidino-1H-benzimidazole -2-yl) ethyl] -6- (2-naphth-1-ylethylcarbamoyldiben Zoimidazol-1-yl] propane-1-sulfonic acid (compound 163), MS (BioIo n) C₃₄H₃₄N₈O₁Sm / e calculated 638.7; found 639.2 (MH⁺);   3- {2- [1- (5-imidazol-1-yl-1H-benzimidazole -2-yl) ethyl] -6- (2-naphth-1-ylethylcarbamoyldiben Zoimidazol-1-yl] propane-1-sulfonic acid (compound 164), MS (BioIo n) C₃₅H₃₃N₇O_FourSm / e calculated value 647.8; measured value 648.2 (MH⁺);   2- [1- (5-guanidino-1H-benzimidazol-2-yl) -2- Methylpropyl] -3-methyl-N- (2-naphth-1-ylethyl) -3H- Benzimidazole-5-carboxamide (compound 165), MS (BioIon) C₃₃H₃₄ N₈O₁m / e calculated 558.7; measured 559.6 (MH⁺);   2- [1- (1H-imidazo [4,5-c] pyridin-2-yl) ethyl]- 3-methyl-N- (2-naphth-1-ylethyl) -3H-benzimidazole -5-carboxamide (compound 166), MS (BioIon) C₂₉H₂₆N₆O₁m / e calculated value 4 74.6; Found 475.2 (MH⁺);   2- {5- [1- (N-methylimino) ethyl] -4,5,6,7-tetrahi Dro-1H-imidazo [4,5-c] pyridin-2-ylmethyl} -3-methyl -N- (2-naphth-1-ylethyl) -3H-benzimidazole-5-cal Boxamide (compound 167), MS (BioIon) C₃₁H₃₃N₇Om / e calculated 519.71; Value 520.9 (MH⁺);   Imino (2- {1- [1-methyl-6- (2-naphth-1-ylethylcarba) Moyl) -1H-benzimidazol-2-yl] d Tyl｝ -1,4,6,7-tetrahydroimidazo [4,5-c] pyridine-5- Il) Acetic acid (compound 168), MS (BioIon) C₃₁H₃₁N₇O_Threem / e calculated value 549.6; Value 550.2 (MH⁺);   2- {1- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1 H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3-methyl-N- (2-Naphth-1-ylethyl) -3H-benzimidazole-5-carboxa Mido (compound 169), MS (BioIon) C₃₁H₃₃N₇O₁m / e calculated 519.6; found 520. 3 (MH⁺);   2- {1- [5- (N-methylamino) -4,5,6,7-tetrahydro-1 H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3-methyl-N- (2-Naphth-1-ylethyl) -3H-benzimidazole-5-carboxa Mid (Compound 170), MS (BioIon) C₃₁H₃₄N₈O₁m / e calculated 534.7; found 535. 1 (MH⁺);   2- (2- {2- [1- (5-guanidino-1H-benzimidazole-2- Yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcarbonyl Amino diethoxy) -5-methoxybenzoic acid (compound 171), MS (BioIon) C₂₉H_{Two 8} N₈O_Fivem / e calculated 570.6; found 571.2 (MH⁺);   2- (2- {2- [1- (5-guanidino-1H-benzimidazole-2- Yl) ethyl] -3-methyl-3H-benzimidazole-5-carbonylamido Nodethoxy) isophthalic acid (compound 172), MS (BioIon) C₂₉H₃₀N₈O_Fivem / e Calculated 570.6; Found 571.3 (MH⁺);   2- (2- {2- [1- (5-guanidino-1H-benzimidazole-2- Yl) -1-hydroxyethyl] -3-methyl-3H -Benzimidazol-5-ylcarbonylaminodiethoxy) -6-methoxy Benzoic acid (compound 173), MS (BioIon) C₂₉H₃₀N₈O₆m / e calculated value 586.6; 587.2 (MH⁺);   Ethyl 2- [2- (2- {1- [5- (N-acetylguanidino) -1H-beta] [Nazoimidazol-2-yl] ethyl} -3-methyl-3H-benzimidazo Ru-5-ylcarbonylamino) ethoxy] benzoate (compound 174), MS (Bio Ion) C₃₁H₃₂N₈O_Fivem / e calculated 596.6; found 597.2 (MH⁺);   2- {1- [5- (N, N-dimethylamidino) -4,5,6,7-tetrahydrido B-1H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3-methyl -N- (2-naphth-1-ylethyl) -3H-benzimidazole-5-cal Boxamide (compound 175);   2- {1- [5- (2-amino-1,1-dimethylethyl) -1H-benzoi Midazol-2-yl] ethyl} -3-methyl-N- (2-naphth-1-yl Tyl) -3H-benzimidazole-5-carboxamide (Compound 176);   2- {1- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1 H-imidazo [4,5-c] pyridin-2-yl] ethyl} -N-ethyl-3- Methyl-3H-benzimidazole-5-carboxamide (compound 177);   2- [2- (2- {1- [5- (N-acetylguanidino) -1H-benzoi] Midazol-2-yl] ethyl} -3-methyl-3H-benzimidazol-5 -Ylcarbonylamino) ethoxy] benzoic acid (compound 178), MS (BioIon) C₃₀ H₃₀N₈O_Fivem / e calculated 582.6; actual 583.3 (MH⁺);   2- [2- (2- {1- [5- (1-aminocyclopropyl)-] 1H-benzimidazol-2-yl] ethyl} -3-methyl-3H-benzoi Midazol-5-ylcarbonylamino) ethoxy] benzoic acid (compound 179), MS (BioIon) C₃₀H₃₀N₆O_Fourm / e calculated 538.6; found 539.3 (MH⁺);   2- [1- (5-imidazol-1-yl-1H-benzimidazole-2- Yl) ethyl] -3-methyl-N- (3-methylbutyl) -3H-benzimida Sol-5-carboxamide (compound 180); MS (BioIon) C₂₆H₂₉N₇O₁m / e Calculated value 455.6; measured value 456.2 (MH⁺);   2- (1H-benzimidazol-2-ylethyl) -3-methyl-N- (2 -Phenoxyethyl) -3H-benzimidazole-5-carboxamide (compound 181), MS (BioIon) C₂₆H_{twenty five}N_FiveO_Twom / e calculated 439.5; found 440.2 (MH⁺);   Ethyl 2- [2- (2- {1- [5- (1-iminoethyl) -4,5,6,7 -Tetrahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl -3-methyl-3H-benzimidazol-5-ylcarbonylamino) ethoxy B] benzoate (compound 182);   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -3-methyl-N- [2- (2,4-dioxo-3,4-dihydro-2H-ki Nazolin-1-yl) ethyl] -3H-benzimidazole-5-carboxami (Compound 183);   2- {1- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1 H-imidazo [4,5-c] pyridin-2-yl] ethyl} -N- (3-methoxy (Cipropyl) -3-methyl-3H-benzimidazole-5-carboxamide ( Compound 184);   N-ethyl-2- [1- (5-imidazol-1-yl-1H- Benzimidazol-2-yl) ethyl] -3-methyl-3H-benzimidazo -5-carboxamide (compound 185), MS (BioIon) C_{twenty three}H_{twenty three}N₇O₁m / e meter Calculated 413.5; Found 414.1 (MH⁺);   2- [1- (5-imidazol-1-yl-1H-benzimidazole-2- Yl) ethyl] -N- (2-methoxyethyl) -3-methyl-3H-benziimi Dazol-5-carboxamide (compound 186); MS (BioIon) C_{twenty four}H_{twenty five}N₇O_Twom / e Calculated 443.5; Found 444.2 (MH⁺);   1- {2- [1- (5-imidazol-1-yl-1H-benzimidazole -2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcar Bonylamino} -4-methylpentanoic acid (compound 187), MS (BioIon) C₂₇H₂₉N₇ O_Threem / e calculated 499.6; found 500.3 (MH⁺);   2- (2- {2- [1- (5-imidazol-1-yl-1H-benzimidida) Zol-2-yl) ethyl] -3-methyl-3H-benzimidazol-5-i Lecarbonylaminodiethoxy) benzoic acid (compound 188), MS (BioIon) C₃₀H₂₇ N₇O_Fourm / e calculated 549.6; found 550.2 (MH⁺);   2- (2- {1- [5- (1-iminoethyl) -4,5,6,7-tetrahydrido B-1H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3-methyl -3H-benzimidazol-5-ylcarbonylamino) -4-methylpenta Acid (compound 189);   2- {1- [5- (N, N-dimethylamidino) -4,5,6,7-tetrahi Dro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl {3-methyl -3H-benzimidazol-5-ylcarbonylamino) ethoxy] benzoic acid (Compound 190), MS (BioIon) C₃₉H₃₄N₈O_Fourm / e calculated 558.6; found 559.3 (MH⁺ );   2- [2- (2- {1- [5- (2-carboxy-1-iminoethyl) -4, 5,6,7-tetrahydro-1H-imidazo [4,5-c] pyridin-2-yl Ethyl} -3-methyl-3H-benzimidazol-5-ylcarbonylamido G) ethoxy] benzoic acid (compound 181), MS (BioIon) C₂₉H₃₁N₇O₆m / e calculation Value 573.6; measured value 530.3 (MH^-) 、 CO_TwoLoss of   2- (2- {2- [1- (5-imidazol-1-yl-1H-benzimidida) Zol-2-yl) ethyl] -3- (2-methoxyethyl) -3H-benzimi Dazol-5-ylcarbonylaminodiethoxy) benzoic acid (compound 192), MS (B ioIon) C₃₂H₃₁N₇O_Fivem / e calculated 593.6; found 594.2 (MH⁺);   2- [1- (5-imidazol-1-yl-1H-benzimidazole-2- Yl) ethyl] -3- (2-methoxyethyl) -N- (2-methoxyethyl)- 3H-benzimidazole-5-carboxamide (compound 193), MS (BioIon) C_{Two Five} H₂₉N₇O_Threem / e calculated 487.6; found 488.2 (MH⁺);   2- [2- (2- {1- [5- (1-iminoethyl-4,5,6,7-tetra Hydro-1H-inidazo [4,5-c] pyridin-2-yl] ethyl} -3- ( 2-methoxyethyl) -3H-benzimidazol-5-ylcarbonylamino ) Ethoxy] benzoic acid (compound 194);   3- (2- {2- [1- (5-guanidino-1H-benzimidazole-2- Yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcarbonyl Aminodiethoxy) benzoic acid (compound 185), MS (BioIon) C₂₈H₂₈N₈O_Fourm / e Calculated value 540.6; measured value 541.3 (MH⁺);   2- (2- {2- [1- (5-guanidino-1H-benzimidida) Zol-2-yl) ethyl] -3- (2-methoxyethyl) -3H-benzimi Dazol-5-ylcarbonylaminodiethoxy) benzoic acid (compound 196), MS (B ioIon) C₃₀H₃₂N₈O_Fivem / e calculated 584.6; found 585.3 (MH⁺);   2- (2- {2- [1- (5-guanidino-1H-benzimidazole-2- Yl) ethyl] -3- (3-sulfopropyl) -3H-benzimidazole-5 -Ylcarbonylaminodiethoxy) benzoic acid (compound 197), MS (BioIon) C₃₀ H₃₂N₈O₇Sm / e calculated 648.7; found 649.6 (MH⁺);   2- (2- {2- [1- (5-imidazol-1-yl-1H-benzimidida) Zol-2-yl) ethyl] -3- (3-sulfopropyl) -3H-benzoimid Dazol-5-ylcarbonylaminodiethoxy) benzoic acid (compound 198), MS (B ioIon) C₃₂H₃₁N₇O₇Sm / e calculated 657.7; found 658.4 (MH⁺);   2- (2- {2- [1- (5-imidazol-1-yl-3-methyl-3H- Benzimidazol-2-yl) ethyl] -3-methyl-3H-benzimidazo Yl-5-ylcarbonylaminodiethoxy) benzoic acid (compound 199), MS (BioIo n) C₃₁H₂₉N₇O_Fourm / e calculated 563.6; found 564.2 (MH^-);   2- (2- {2- [1- (5-imidazol-1-yl-1H-benzimidida) Zol-2-yl) ethyl] -3- (2-hydroxypropyl) -3H-benzo Imidazol-5-ylcarbonylaminodiethoxy) benzoic acid (compound 200), M S (BioIon) C₃₂H₃₁N₇O_Fivem / e calculated 593.6; found 564.3 (MH⁺);   2- {2- [2- (1- {5- [1- (N-hydroxyimino) ethyl] -4 "] , 5,6,7-Tetrahydro-1H-imidazo [4,5-c] pyridine-2-i (Ruethyl) -3-methyl-3H-ben Zoimidazol-5-ylcarbonylamino] ethoxydibenzoic acid (Compound 201) ;   Ethyl 2- (2- {2- [1- (5-guanidino-1H-benzimidazole) -2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcar Bonylaminodiethoxy) benzoate (Compound 202), MS (BioIon) C₃₀H₃₂N₈ O_Fourm / e calculated 568.6; found 569.5 (MH⁺);   Ethyl 2- [2- (2- {1- [5- (1-iminoethyl) -4,5,6,7 -Tetrahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl -1,4,6,7-tetrahydroimidazo [4,5-c] pyridin-5-dolphin Rubonylamino) ethoxy] benzoate (compound 203), MS (BioIon) C₂₈H₃₆ N₈O_Fourm / e calculated 549.0; found 548.2 (MH⁺);   Ethyl 4- {2- [1- (5-guanidino-1H-benzimidazole-2- Yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcarbonyl Amino dibutyrate (compound 204), MS (BioIon) C_{twenty five}H₃₀N₈O_Threem / e calculated value 490 .57; found 491.3 (MH⁺);   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -3-Methyl-N- [2- (2-tetrazol-1-ylphenoxy) ethyl ] -3H-benzimidazole-5-carboxamide (Compound 205), MS (BioIo n) C₂₈H₂₈N₁₂O_Twom / e calculated 564.56; found 565.3 (MH⁺);   2- [2- (2- {1- [5- (1-Iminoethylamino) -1H-benzoi] Midazol-2-yl] ethyl} -3-methyl-3H-benzimidazol-5 -Ylcarbonylamino) ethoxy] benzoic acid (compound 206), MS (BioIon) C₃₁ H₃₃N₇O_Fourm / e calculated value 567.6; actual value 568.4 (MH⁺);   Ethyl 4- (2- {2- [1- (5-guanidino-1H-benzimidazole) -2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcar Bonylaminodiethoxy) benzoate (Compound 207), MS (BioIon) C₃₀H₃₂N₈ O_Fourm / e calculated 568.6; found 569.4 (MH⁺);   5- (2- {2- [1- (5-guanidino-1H-benzimidazole-2- Yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcarbonyl Amino diethoxy) isophthalic acid (compound 208), MS (BioIon) C₂₉H₂₈N₈O₆m / E calculated 584.6; found 585.3 (MH⁺);   4- (2- {2- [1- (5-guanidino-1H-benzimidazole-2- Yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcarbonyl Amino diethoxy) benzoic acid (Compound 209), MS (BioIon) C₂₈H₂₈N₈O_Fourm / e Calculated value 540.6; measured value 541.2 (MH⁺);   2- (2- {2- [1- (5-guanidino-1H-benzimidazole-2- Yl) ethyl] -3- (2-hydroxypropyl) -3H-benzimidazole -5-ylcarbonylaminodiethoxy) benzoic acid (compound 210), MS (BioIon) C₃₀H₃₂N₈O_Fivem / e calculated 584.6; found 585.4 (MH⁺);   2- [1- (5-imidazol-1-yl-1H-benzimidazole-2- Yl) ethyl] -3-methyl-N- [2- (2-methoxyphenoxy) ethyl] -3H-benzimidazole-5-carboxamide (compound 211), MS (BioIon) C₃₀H₂₉N₇O_Twom / e calculated 535.6; found 536.3 (MH⁺);   2- (2- {2- [1- (5-guanidino-1H-benzimidida) Zol-2-yl) ethyl] -3-methyl-3H-benzimidazol-5-i Lecarbonylaminodiethoxy) benzoic acid (compound 212), MS (BioIon) C₂₇H₂₆ N₈O_Fourm / e calculated 526.6; found 527.2 (MH⁺);   2- [1- (5-imidazol-1-yl-1H-benzimidazole-2- Yl) ethyl] -3-methyl-N- (2-phenoxyethyl) -3H-benzoi Midazole-5-carboxamide (compound 213), MS (BioIon) C₂₉H₂₇N₇O_Twom / E calculated 505.6; measured 506.2 (MH⁺);   2- (2- {2- [1- (5-imidazol-1-yl-1H-benzimidida) Zol-2-yl) ethyl] -1H-benzimidazol-5-ylcarbonyl Aminodiethoxy) benzoic acid (Compound 214), MS (BioIon) C₂₉H_{twenty five}N₇O_Fourm / e Calculated 535.6; Found 536.4 (MH⁺);   Ethyl 2- (2- {2- [1- (5-guanidino-1H-benzimidazole) -2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcar Bonylaminodiethoxy) -4-methylbenzoate (Compound 215), MS (BioIon ) C₃₁H₃₄N₈O_Fourm / s calc. 582.7; found 583.5 (MH⁺);   2- (2- {2- [1- (5-guanidino-1H-benzimidazole-2- Yl) ethyl] -3-methyl-benzimidazol-5-ylcarbonylamino {Ethoxy) -4-methylbenzoic acid (Compound 216), MS (BioIon) C₂₉H₃₀N₈O_Four m / e calculated 554.6; found 555.5 (MH⁺);   2- [2- (2- {1- [5- (1-iminoethyl) -4,5,6,7-tetra] Lahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl} -1, 4,6,7-tetrahydroimidazo [4 , 5-c] pyridin-5-ylcarbonylamino) ethoxy] benzoate Compound 217), MS (ESI) C₂₆H₃₂N_ThreeO_Fourm / e calculated 520.58; found 521.3 (MH⁺);   Ethyl 2- (2- {2- [5- (N-methylamidino) -1H-benzimidida Zol-2-ylmethyl] -3-methyl-3H-benzimidazol-5-yl Carbonylaminodiethoxy) benzoate (compound 218), MS (BioIon) C₃₀H_{Three 1} N₇O_Fourm / e calculated 553.6; found 554.3 (MH⁺);   2- [2- (2- {1- [5- (1-iminoethyl) -4,5,6,7-tetra] Lahydro-1H-imidazole [4,5-c] pyridin-2-yl] ethyl}- 3- (3-sulfopropyl) -3H-benzimidazol-5-ylcarbonyl Amino) ethoxy] benzoic acid (compound 219), MS (BioIon) C₃₀H₃₅N₇O₇m / e Calculated value 637.7; measured value 638.3 (MH⁺);   Ethyl 2- (2- {1- [5- (1-iminoethyl) -4,5,6,7-tet Lahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3- Methyl-3H-benzimidazol-5-ylcarbonylamino) -4-methyl Valerate (compound 220); ethyl 2- {2- [2- (1- {5- [1- (N- (Hydroxyimino) ethyl-4,5,6,7-tetrahydro-1H-imidazo [ 4,5-c] pyridin-2-yl @ ethyl] -3-methyl-3H-benzimidida Zol-5-ylcarbonylamino] ethoxy) benziate (compound 221);   2- [1- (1H-benzimidazol-2-yl) ethyl] -3-methyl- N- [2- (2-methoxyphenoxy) ethyl] -3H-benzimidazole- 5-carboxamide (compound 222), MS (BioIon) C₂₇H₂₇N_FiveO_Threem / e calculated value 469 .5; found 469.5 (MH⁺ );   2- (2-ethoxycarbonylphenoxy) ethyl 2- [1- (6-guanidinium) No-1H-benzimidazol-2-yl) ethyl] -1,4,6,7-tetra Hydroimidazo [4,5-c] pyridine-5-carboxylate (compound 223), M S (BioIon) C₂₈H₃₂N₈O_Fivem / e calculated 560.62; found 561.3 (MH⁺);   4- {2- [1- (5-guanidino-1H-benzimidazol-2-yl) Ethyl] -3-methyl-3H-benzimidazol-5-ylcarbonylamino ｝ Butyric acid (compound 224), MS (BioIon) C_{twenty two}H₂₆N₈O_Threem / e calculated 462.52; found 4 62.8 (MH⁺);   2- {1- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1 H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3-methyl-N- [2- (2-tetrazolylphenoxy) ethyl] -3H-benzimidazole- 5-carboxamide (compound 225), MS (ESI) C₂₈H₃₁N₁₁O_Twom / e calculated 553.6; 555.5 (MH⁺);   Isopropyl 2- (2- {2- [1- (5-imidazol-1-yl-1H- Benzimidazol-2-yl) ethyl] -3-methyl-3H-benzimidazo Yl-5-ylcarbonylaminodiethoxy) benzoate (compound 226), MS (B ioIon) C₃₃H₃₃N₇O_Fourm / e calculated 591.3; found 591.4 (MH⁺);   2- {1- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1 H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3-methyl-N- [2- (3-tetrazolylphenoxy) ethyl] -3H-benzimidazole- 5-carboxamide (compound 227), MS (BioIon) C₂₈H₃₁N₁₁O_Twom / e calculated value 55 3.59; actual value 553.5 (MH⁺);   2- {1- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1 H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3-methyl-N- [2- (4-tetrazolylphenoxy) ethyl] -3H-benzimidazole- 5-carboxamide (compound 228), MS (ESI) C₂₈H₃₁N₁₁O_Twom / e calculated value 553.5 9; actual value 553.5 (MH⁺);   Cyclohexyl 2- (2- {2- [1- (5-imidazol-1-yl) -1] [H-benzimidazol-2-yl] ethyl} -3-methyl-3H-benzimi Dazol-5-ylcarbonylamino) ethoxybenzoate (Compound 229), MS (ESI) C₃₆H₃₇N₇O_Fourm / e calculated 631.3; found 631.5 (MH⁺);   2- [2- (2- {1- [5- (N-methylamidino) -1H-benzimidida] Zol-2-yl] ethyl} -3-methyl-3H-benzimidazol-5-i Rucarbonylamino) ethoxy] benzoic acid (compound 230), MS (BioIon) C₂₈H₂₇ N₇O_Fourm / e calculated 525.6; found 525.5 (MH⁺);   2- [2- (2- {1- [5- (1-Iminoethylamino) -1H-benzoi] Midazol-2-yl] ethyl} -3-methyl-3H-benzimidazol-5 -Ylcarbonylamino) ethoxy] benzoic acid (compound 231), MS (BioIon) C₂₉ H₂₉N₇O_Fourm / e calculated 539.6; found 539.8 (MH⁺);   2- (3- {2- [1- (5-guanidino-1H-benzimidazole-2- Yl) ethyl] -1,4,6,7-tetrahydroimidazo [4,5-c] pyridi N-5-ylcarbonyl {propoxy) benzoic acid (compound 232), MS (BioIon) C_{Two 7} H₃₀N₈O_Fourm / e calculated 530.60; found 531.7 (MH⁺);   2- (2- {2- [1- (5-guanidino-1H-benzimidida) Zol-2-yl) ethyl] -1,4,6,7-tetrahydroimidazo [4,5 -C] pyridin-5-ylformyloxydiethoxy) benzoic acid (compound 233), M S (BioIon) C₂₆H₂₈N₈O_Fivem / e calculated 532.56; found 533.2 (MH⁺);   2-methoxyethyl 2- (2- {2- [1- (5-imidazol-1-yl)] -1H-benzimidazol-2-yl] ethyl] -3-methyl-3H-benzo Imidazol-5-ylcarbonylaminodiethoxy) benzoate (compound 234) ), MS (BioIon) C₃₃H₃₃N₇O_Fivem / e calculated 607.3; found 607.4 (MH⁺);   Isobutyl 2- (2- {2- [1- (5-imidazol-1-yl) -1H- Benzimidazol-2-yl] ethyl} -3-methyl-3H-benzimidazo Yl-5-ylcarbonylaminodiethoxy) benzoate (compound 235), MS (B ioIon) C₃₄H₃₅N₇O_Fourm / e calculated 605.3; measured 605.4 (MH⁺);   2- (2-methoxyethoxy) ethyl 2- (2- {2- [1- (5-imidazo) 1-yl-1H-benzimidazol-2-yl) ethyl] -3-methyl -3H-benzimidazol-5-ylcarbonylaminodiethoxy) benzoe (Compound 236), MS (BioIon) C₃₅H₃₇N₇O₆m / e calculated 651.3; found 651. 3 (MH⁺);   Butyl 2- (2- ｛2 = [1- (5-imidazol-1-yl-1H-benzo) Imidazol-2-yl) ethyl] -3-methyl-3H-benzimidazole- 5-ylcarbonylaminodiethoxy) benzoate (compound 237), MS (BioIon ) C₃₄H₃₅N₇O_Fourm / e calculated 605.3; measured 605.4 (MH⁺);   2- [1- (1H-benzimidazol-2-yl) ethyl] -3-methyl- N- [2- (3-oxo-2,3-dihydrobenzo [ 1,4] oxazin-4-yl) ethyl] -3H-benzimidazole-5-ca Luboxamide (compound 238), MS (BioIon) C₂₈H₂₆N₈O_Threem / e calculated 494.2; actual Measurement 494.5 (MH⁺);   2- [1- (1H-benzimidazol-2-yl) ethyl] -3-methyl- N- [2- (2-fluorophenoxy) ethyl] -3H-benzimidazole- 5-carboxamide (compound 239);   2- [1- (1H-benzimidazol-2-yl) ethyl] -3-methyl- N- [2- (3-fluorophenoxy) ethyl] -3H-benzimidazole- 5-carboxamide (Compound 240);   2- [1- (1H-benzimidazol-2-yl) ethyl] -3-methyl- N- [2- (2-isopropoxyphenoxy) ethyl] -3H-benzimidazo -5-carboxamide (Compound 241), MS (BioIon) C₂₉H₃₁N_FiveO_Threem / e meter Calculated 497.2; Found 497.6 (MH⁺);   2- [1- (1H-benzimidazol-2-yl) ethyl] -3-methyl- N- [2- (2-methylphenoxy) ethyl] -3H-benzimidazole-5 -Carboxamide (compound 242), MS (BioIon) C₂₇H₂₇N_FiveO_Twom / e calculated value 453.2 ; Measured 453.5 (MH⁺);   2- [1- (1H-benzimidazol-2-yl) ethyl] -3-methyl- N- [2- (2-ethoxyphenoxy) ethyl] -3H-benzimidazole- 5-carboxamide (compound 243), MS (BioIon) C₂₈H₂₉N_FiveO_Threem / e calculated value 483 .2; Actual value 483.5 (MH⁺);   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -3-Methyl-N- [2- (2-methoxyphenoxy) ethyl] -3H-ben Zoimidazole-5-carboxamide ( Compound 244), MS (BioIon) C₂₈H₃₀N₈O_Threem / e calculated 526.6; found 526.8 (MH⁺ );   Ethyl 2- (2- {2- [1- (5-guanidino-1H-benzimidazole) -2-yl) ethyl] -1,4,6,7-tetrahydroimidazo [4,5-c] Pyridin-5-ylcarbonylaminodiethoxy) benzoate (compound 245), M S (BioIon) C₂₈H₃₃N₉O_Fourm / e calculated 559.6; measured 559.6 (MH⁺);   2-methoxyethyl 2- (2- {2- [1- (1H-benzimidazole-2) -Yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcarboni Ruaminodiethoxy) benzoate (compound 246), MS (BioIon) C₃₀H₃₁N_FiveO_Four m / e calculated 541.6; found 541.5 (MH⁺);   Ethyl 2- (2- {2- [1- (5-guanidino-1H-benzimidazole) -2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcar Bonylaminodiethoxy) benzoate (Compound 247), MS (BioIon) C₂₉H₃₀N₈ O_Fourm / e calculated 554.6; found 555.4 (MH⁺);   2- (2- {2- [1- (5-guanidino-1H-benzimidazole-2- Yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcarbonyl Aminodiethoxy) benzoic acid (compound 248), MS (BioIon) C₂₈H₂₆N₈O_Fourm / e Calculated value 540.6; measured value 541.3 (MH⁺);   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -N- [2- (2-carbamoylphenoxy) ethyl] -3-methyl-3H- Benzimidazole-5-carboxamide (Compound 249), MS (BioIon) C₂₈H₂₉ N₉O_Threem / e calculated 539.6; found 540.5 (MH⁺);   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -N- [2- (2-carbamoyl-4-chlorophenoxy) ethyl] -3-me Tyl-3H-benzimidazole-5-carboxamide (Compound 250), MS (BioIo n) C₂₈H₂₈N₉O_ThreeCl m / e calculated 574.0; found 574.2 (MH⁺);   4-chloro-2- (2- {2- [1- (5-guanidino-1H-benzimidida) Zol-2-yl) ethyl] -3-methyl-3H-benzimidazol-5-i Lecarbonylaminodiethoxy) benzoic acid (compound 251), MS (BioIon) C₂₈H₂₇ N₈O_FourCl m / e calculated 575.0; found 575.2 (MH⁺);   5-chloro-2- (2- {2- [1- (5-guanidino-1H-benzimidida) Zol-2-yl) ethyl] -3-methyl-3H-benzimidazol-5-i Lecarbonylaminodiethoxy) benzoic acid (compound 252), MS (BioIon) C₂₈H₂₇ N₈O_FourCl m / e calculated 575.0; found 575.2 (MH⁺);   6-chloro-2- (2- {2- [1- (5-guanidino-1H-benzimidida) Zol-2-yl) ethyl] -3-methyl-3H-benzimidazol-5-i Lecarbonylaminodiethoxy) benzoic acid (compound 253), MS (BioIon) C₂₈H₂₇ N₈O_FourCl m / e calculated 575.0; found 575.2 (MH⁺);   4,6-dichloro-2- (2- {2- [1- (5-guanidino-1H-benzo) Imidazol-2-yl) ethyl] -3-methyl-3H-benzimidazole- 5-ylcarbonylaminodiethoxy) benzoic acid (compound 254), MS (BioIon) C_{Two 8} H₂₆N₈O_FourCl_Twom / e calculated 609.5; found 609.1 (MH⁺);   Ethyl 2- (2- {2- [1- (1H-benzimidazol-2-yl) ethyl) 3-Methyl-3H-benzimidazole-5 Carbonylaminodiethoxy) benzoate (Compound 255), MS (BioIon) C₂₉N_{Two 9} N₆O_Fourm / e calculated 511.6; found 512.2 (MH⁺);   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -3-methyl-N- {2- [2,4-dioxo-3- (2-trimethylsilani Ruethyl) -3,4-dihydro-2H-quinazolin-1-yl] ethyl @ -3H -Benzimidazole-5-carboxamide (compound 256), MS (BioIon) C₃₄H_{Four 0} N_TenO₈Sim / e calculated 664.8; found 665.4 (MH⁺);   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -3-Methyl-N- {2- [2,4-dioxo-3,4-dihydro-2H-ki Nazolin-1-yl] ethyl} -3H-benzimidazole-5-carboxami (Compound 257), MS (BioIon) C₂₉H₂₈N_TenO_Threem / e calculated 564.6; found 565.2 (MH⁺);   2- [1- (1H-benzimidazol-2-yl) ethyl] -N- [2- ( 2-cyanophenoxy) ethyl] -3-methyl-3H-benzimidazole-5 -Carboxamide (compound 258), MS (BioIon) C₂₇H_{twenty four}N₆O_Twom / e calculated value 454.5 ; Actual value 465.1 (MH⁺);   5- (2- {2- [1- (1H-benzimidazol-2-yl) ethyl]- 3-methyl-3H-benzimidazol-5-ylcarbonylaminodiethoxy ) Isophthalic acid (compound 259), MS (BioIon) C₂₈H_{twenty five}N_FiveO₆m / e calculated 527.5; Actual 528.4 (MH⁺);   2- (2-methoxyethoxy) ethyl 2- (2- {2- [1- (1H-benzo) Imidazol-2-yl) ethyl] -3-methyl-3H-benzimidazole- 5-ylcarbonylaminodiethoxy) benzoate (Compound 260), MS (BioIon ) C₃₂H₃₅N_FiveO₆m / e Calculated 585.7; found 585.4 (MH⁺);   2- (2- {2- [1- (5-guanidino-1H-benzimidazole-2- Yl) ethyl] -1,4,6,7-tetrahydroimidazo [4,5-c] pyrido -5-ylcarbonylaminodiethoxy) benzoic acid (compound 261), MS (BioIon) C₂₉H₂₉N₉O_Fourm / e calculated 531.6; found 531.5 (MH⁺);   2- [1- (1H-imidazo [4,5-c] pyridin-2-yl) ethyl]- N- [2- (2-methoxyphenoxy) ethyl] -3-methyl-3H-benzoi Midazole-5-carboxamide (Compound 262), MS (BioIon) C₂₆H₂₆N₆O_Threem / E calculated 470.54; found 471.4 (MH⁺);   2- [1- (5-fluoro-1H-benzimidazol-2-yl) ethyl] -N- [2- (2-methoxyphenoxy) ethyl] -3-methyl-3H-benzo Imidazole-5-carboxamide (compound 263), MS (BioIon) C₂₇H₂₆N₆O_Three F m / e calculated 487.54; found 488.1 (MH⁺);   2- [1- (5-imidazol-1-yl-1H-benzimidazole-2- Yl) ethyl] -3-methyl-N- (2-tetrazol-1-ylethyl) -3 H-benzimidazole-5-carboxamide (compound 264), MS (ESI) C_{twenty four}H_{twenty three}N₁₁ O m / e calculated 481.47; found 482.6 (MH⁺);   2- [1- (4-hydroxy-1H-benzimidazol-2-yl) ethyl ] -N- [2- (2-methoxyphenoxy) ethyl] -3-methyl-3H-ben Zoimidazole-5-carboxamide (Compound 265), MS (BioIon) C₂₇H₂₇N_FiveO_Four m / e calculated 485.59; found 486.3 (MH⁺);   2- [1- (4-aminobenzoxazol-2-yl) ethyl] -N- [2- (2-methoxyphenoxy) ethyl] -3-methyl-3H-benzo Imidazole-5-carboxamide (compound 266), MS (BioIon) C₂₇H₂₇N₆O_Four m / e calc. 485.59; found 486.1 (MH⁺);   3- {2- [1- (1H-benzimidazol-2-yl) ethyl] -6- [ 2- (2-methoxyphenoxy) ethylcarbamoyl] benzimidazole-1 -Yl) propane-1-sulfonic acid (compound 267), MS (BioIon) C₂₉H₃₁N_FiveO₆ Sm / e calculated 577.66; found 577.4 (MH⁺);   3- {2- [1- (5-imidazol-1-yl-1H-benzimidazole -2-yl) ethyl] -6- [2- (2-methoxyphenoxy) ethylcarbamo Yl] benzimidazol-1-yl} propane-1-sulfonic acid (compound 268) , MS (BioIon) C₃₂H₃₃N₇O₆Sm / e calculated 643.72; found 644.6 (MH⁺);   Ethyl 2- [2- (2- {1- [1- (2-methoxyethyl) -1H-benzo] [Imidazol-2-yl] ethyl} -3-methyl-3H-benzimidazole- 5-carbonylamino) ethoxy] benzoate (compound 269), MS (BioIon) C_{Three Two} H₃₅N_FiveO_Fivem / e calculated 569.66; found 570.5 (MH⁺);   Benzyl 2- [1- (5-imidazol-1-yl-1H-benzimidazo) Ru-2-yl) ethyl] -1,4,6,7-tetrahydroimidazo [4,5-c Pyridine-5-carboxylate (compound 270), MS (BioIon) C₃₀H₃₀N₈O₆ m / e calculated 586.6; found 587.2 (MH⁺);   Ethyl 2- (4- {2- [1- (1H-benzimidazol-2-yl) ethyl) 1,4,6,7-tetrahydroimidazole [4,5-c] pyridine-5 -Yl} -4-oxobutoxy) benzo Eate (compound 271);   1- {2- [1- (1H-benzimidazol-2-yl) ethyl] -1,4 , 6,7-Tetrahydroimidazo [4,5-c] pyridin-5-yl} -4- ( 2-methoxyphenoxy) butan-1-one (compound 272);   2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -N- (2-Naphth-1-ylethyl) imidazo [1,2-a] pyridine-6-carbo Oxamide (compound 273);   N- [3- (2-ethoxyphenyl) propyl] -2- [1- (5-hydroxy C-1H-benzimidazol-2-yl) ethyl] -3-methyl-3H-ben Zoimidazole-5-carboxamide (compound 274), MS (BioIon) C₂₉H₃₁N_FiveO_Three m / e calculated 497.62; found 497.4;   N- [3- (2-butoxyphenyl) propyl] -2- [1- (5-hydroxy C-1H-benzimidazol-2-yl) ethyl] -3-methyl-3H-ben Zoimidazole-5-carboxamide (compound 275), MS (BioIon) C₃₁H₃₅N_FiveO_Three m / e calculated 525.65; found 526.3;   2- [1- (5-hydroxy-1H-benzimidazol-2-yl) ethyl ] -3-Methyl-N- [3- (2-propoxyphenyl) propyl] -3H- Nzoimidazole-5-carboxamide (compound 276), MS (BioIon) C₃₀H₃₃N_Five O_Threem / e calc. 511.62; found 512.3;   2- [1- (5-hydroxy-1H-benzimidazol-2-yl) ethyl ] -N- {2- [2- (3-methyl- [1,2,4] oxadiazole-5-i Ru) phenoxy] ethyl} -3-methyl-3H-benzimidazole-5-car Boxamide (compound 277), MS (BioIon) C₂₉H₂₇N₇O_Fourm / e calculated 538.1; found 537.58;   Ethyl 2- (2- {2- [1- (4-fluoro-5-hydroxy-1H-benzene) Zoimidazol-2-yl) ethyl {-3-methyl-3H-benzimidazole -5-ylcarbonylaminodiethoxy) benzoate (compound 278), MS (ESI) C₂₉ H₂₈N_FiveO_Fivem / e calculated 545.57 found 545.6;   2- (2- {2- [1- (4-fluoro-5-hydroxy-1H-benziimi) Dazol-2-yl) ethyl] -3-methyl-3H-benzimidazol-5 Ircarbonylaminodiethoxy) benzoic acid (compound 279), MS (BioIon) C₂₇H_{Two Four} N_FiveO_FiveFm / e calc. 517.52 found 517.4;   Ethyl 2- (2- {2- [1- (6-fluoro-4-hydroxy-1H-ben) Zoimidazol-2-yl) ethyl] -3-methyl-3H-benzimidazole -5-ylcarbonylaminodiethoxy) benzoate (compound 280), MS (BioIo m) C₂₉H₂₈N_ThreeO_FiveFm / e calculated 545.57; found 545.9;   2- (2- {2- [1- (6-fluoro-4-hydroxy-1H-benziimi) Dazol-2-yl) ethyl] -3-methyl-3H-benzimidazol-5 (Ilcarbonylaminodiethoxy) benzoic acid (Compound 280), MS (BioIon) C₂₇H_{Two Four} N_FiveO_FiveFm / e calc. 517.52 found 517.6;   Ethyl 2- (2- {2- [1- (4,5-difluoro-7-hydroxy-1H) -Benzimidazol-2-yl) ethyl] -3-methyl-3H-benzimidida Zol-5-ylcarbonylaminodiethoxy) benzoate (compound 281), MS (BioIon) C₂₉H₂₇N_FiveO_FiveF_Twom / e calculated 563.56 found 563.9; and   2- (2- {2- [1- (4,5-difluoro-7-hydroxy-1H-ben Zoimidazol-2-yl) ethyl] -3-methyl-3H-benzimidazole -5-ylcarbonylaminodiethoxy) benzoic acid (compound 282), MS (ESI) C₂₉H₂₇ N_FiveO_FiveF_Twom / e calc. 536.1 found 535.51.   Example 13.In vitro tryptase inhibition assay   The tryptase solution can be used in a human lung or skin tissue preparation or a human mast cell line (MMC-1). ) Or purified from commercial sources such as ICN Biomeidals, Irvine, California , Athens Research & Technology, Athens, Georgia, etc. Trip obtained from The enzyme was prepared from 10 mM 2-N-morpholinoethanesulfonic acid, 2 mM CaCl 2_Two, 20% grits By dissolving in a solvent mixture comprising serol and 50 g / l heparin Prepared. 2 mM synthetic tripeptide (mesyl-Gly-Pro-Lys-p-nitroanilide ) Was obtained from Sigma. The test compound solution is added to the stock solution (200 μl Test compound (1 mg) in methyl sulfoxide (DMSO) was added to assay buffer (Tris -HCl (pH8.2), 50 mM; NaCl, 100 mM; 0.05% polyoxyethylene sorbitan monola Urate (T Dilute and then further dilute 3 fold with 10% DMSO in assay buffer Prepared by   Aliquots (50 μl) from each of the eight dilutions of the test compound solution were added to 96- Wells were added to separate wells in a U-bottom microtiter plate. bird Putase solution (25 μl) is added to each well and the solution is incubated for 1 hour at room temperature. While mixing. Add the substrate solution (25 μl), start the enzymatic reaction, and Quickly, UV / MAX Kinetic Microplate Reader (Molec ular Devices). Hydrolysis of chromogenic substrate at 405 nm for 5 minutes Spectroscopically tracked during. The initial velocity measurement is advanced by a kinematic analysis program. (Batchki; Pefr Kuzmic, University of Wisconsin, Madiso n, WI). The apparent inhibition constant (Ki) is calculated using the standard mathematical model to determine the enzyme progress curve. Calculated from   As described in this application or by methods known to those skilled in the art, Compounds of the invention were tested for tryptase inhibitory activity:   Compound 1, Ki = 0.09 μM; Compound 12, Ki = 29 μM; Compound 26, Ki = 33 μM M; Compound 27, Ki = 0.6 μM; Compound 28, Ki = 0.00007 μM; Compound 29, Ki = 0.000008 μM; Compound 30, Ki = 0.09 μM; Compound 37, Ki = 0.002 μM; Compound 42, Ki = 0.008 μM; Compound 43, Ki = 0.002 μM; Compound 74, Ki = 0.006 Compound 75, Ki = 0.03 μM; Compound 80, Ki = 0.01 μM; Compound 81, Ki Compound 84, Ki = 2.6 μM; Compound 102, Ki = 0.00007 μM; Compound 112, Ki = 0.0005 μM; Compound 115, Ki = 0.003 μM; Compound 116, Ki = 0 .006 μM; Compound 117, Ki = 0.008 μM; Compound 126, Ki = 0.008 μM; Compound 127, Ki = 0.006 μM; Compound 128, Ki = 0.002 μM; Compound 169, Ki = 0.001 Compound 132, Ki = 0.00002 μM; Compound 134, Ki = 0.00002 μM; Compound 138, Ki = 0.002 μM; compound 152, Ki = 0.0005 μM; compound 182, Ki = 0.0 Compound 194, Ki = 0.09 μM; Compound 203, Ki = 0.008 μM; Compound 22 5, Ki = 0.008 μM; compound 249, Ki = 0.007 μM; compound 250, Ki = 0.0004 μM; compound 251, Ki = 0.008 μM; and compound 252, Ki = 0.0004 μM.   Example 14.Asthma sheep model   The allergic sheep model of asthma according to the present invention is used as an asthma sedative. Used for in vivo evaluation of compounds. Those methods have been published so far (Abraham et al. (1983) Am. Res. Respir. Dis-128: 839-844; Allegra et al. And so on. (1983) J.C. Appl. Physiol. 55: 726-730; Russi et al. (1985) J. Amer. Appl. P hysiol. 59: 1416-1422; Soler et al. (1989) Appl. Physiol. 67: 406-413 checking). Each sheep acts as its own control. Of those animals Body weight ranged from 20 to 50 kg.   In those studies, 1 mg of compound 13 was dissolved in 3 ml of distilled water and total The solution was applied as an aerosol at 0.5 hours before antigen challenge, then 4 and 24 hours. (Total dose = 1 mg; n = 3). The results of those experiments are summarized in FIG. .   24 hours after antigen challenge in both control and drug tests, sheep had a tidal hyperresponse Progressed. Airway hyperresponse is a 400% increase in PC400, or SRL Expressed as the concentration of carbachol causing PCS; PC400 reduction is hyperresponsive Is shown. Compound B was found to block the onset of hyperresponsiveness. Shown in FIG. As shown, this compound substantially maintains PC400 at a baseline value of 15 respiratory units. Was. The number of respiratory units drops to 7 for those animals in the control group did. Thus, treatment with compound 13 has a respiratory tract function in antigen-challenged sheep. Brought significant improvements.   Accordingly, the present invention is directed to immune-mediated inflammatory diseases, particularly diseases associated with the respiratory tract, Examples include asthma and the hyperresponse phase associated with chronic asthma, and allergic nose. Provide compounds and compositions that are useful for preventing and treating flame.   It is understood that the above description is illustrative and not restrictive of the invention. Should be. Many embodiments will be apparent to those skilled in the art from the foregoing description. Follow Accordingly, the scope of the present invention is not limited to the above description. Should not be determined, but instead are subject to the appended claims, and It should be determined by the full scope of equivalents of the following claims.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (Reference) A61P 11/02 A61P 11/02 11/06 11/06 29/00 29/00 31/12 31/12 37 / 08 37/08 43/00 111 43/00 111 C07D 235/02 C07D 235/02 D 235/14 235/14 403/14 403/14 413/14 413/14 471/04 107 471/04 107Z (81 ) Designated countries EP (AT, BE, CH, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG) , CI, CM, GA, GN, ML, MR, NE, SN, TD, TG), AP (GH, KE, LS, MW, SD, SZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AL, AM, T, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, FI, GB, GE, GH, HU, ID, IL, IS , JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, UA, UG, US, UZ, VN, YU, ZW (72) Inventor Cut Char, Neil Scott United States of America, California 94402, San Mateo, A East Fifth Avenue 808 (72) Inventor Ganglov, Anthony Earl. United States, California 94044, Pacifica, Outlook Circle 9 (72) Inventor Jenkins, Thomas -United States, California 94020, La Honda, Box 755, Canada Vista Drive 190 (72) Inventor Linsel, Martin S. United States, California 94404, Foster City, Foster City Boulevard 1103 # 1 (72) Inventor Littbach, Joan United States of America, California 94610, Auckland, Vernon Street 671, Apartment 303 (72) Inventor Rice, Kenneth Dee. United States, California 94965, Sausalito, Tomails Street 7 (72) Inventor Spencer, Jeffrey Earl. United States of America, California 94401 , San Mateo, North El Camino Real 751, Apartment # 101 (72) Inventor One, Vivian Earl. California, United States 94065, Redwood City , Shannon Way 530 # 4215 Substituted by two substituents, R ⁷ is hydrogen or methyl and R ⁸ is hydrogen, methyl or hydroxy.] The compounds, compositions and methods Are inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis, and other types of immune-mediated inflammatory diseases, such as rheumatoid arthritis, conjunctivitis and inflammatory bowel disease, various skin physiological conditions, And is effective for the prevention and treatment of certain viral conditions. The compound comprises a potent and selective inhibitor of mast cell protease tryptase. Compositions for treating these conditions include oral, inhalational and parenteral preparations, and devices comprising such preparations.

Claims (1)

[Claims]   1. Formula I below: Wherein n1 is 0 or 1;   n2 is 0, 1, 2, 3, or 4;   n3 is 0, 1, 2, 3, or 4;   A together with B contains a fused heterobicyclic group containing from 8 to 12 ring atoms. Wherein each ring is from 5 to 7 ring members and each ring atom is optionally May be a terrorist atom, X¹And X^TwoIs an adjacent ring member of an aromatic ring, and X¹Is -N =, -NR^FiveA heteroatom component selected from-, -O- and -S-. Where R^FiveIs hydrogen, (C_1-6) Alkyl or hetero (C_2-4) Is alkyl ;   C is a fused heteropolycyclic group containing from 8 to 18 ring atoms and any carbocyclic Constitute ketone, thioketone and imino ketone derivatives, wherein each ring is 5-7 And each ring atom can be optionally a heteroatom; X^FourPassing And X^FiveIs an adjacent ring member of an aromatic ring;^FiveIs -N-, -NR⁶-, -O- and- A heteroatom component selected from S-, where R⁶Is hydrogen, (C_1-8) Archi Or hetero (C_2-12A group selected from the group consisting of (C)_1-6) Al Canoyloxy, (C_1-6) Alkylamino, di (C_1-6) Alkylamino, tri (C_1-6) Alkyl ammonium, (C_1-6) Alkylcarbamoyl, di (C_1-6) Alkylcarbamoyl, (C_1-6 ) Alkyloxy, (C_1-6) Alkyloxycarbonyl, (C_1-6) Alkylo Xisulfonyl, amino, carboxy, carbamoyl, (C_6-14) Aryl, ha B, hetero (C_5-14) Independently selected from aryl, hydroxy and sulfo (Optionally substituted by one or two substituents) or as defined below Street;   X^ThreeIs -O-, -S-, -S (O)-, -S (O)_Two−, −C (O) −, −NR⁷-Or -CR⁷R⁸ -Where R⁷Is hydrogen, (C_1-6) Alkyl or hetero (C_2-12) Al Kill or R⁶Together with (C_2-4) Alkylene or hetero (C_2-4) Forming an alkylene; and R⁸Is hydrogen, (C_1-6) Alkyl or hydroxy Or R⁷Together with (C_2-6) Alkylene or (C_1-6) Alkylide Where R⁷And / or R⁸Any aliphatic or cycloaliphatic component that constitutes The minute is (C_1-6) Alkylamino, di (C_1-6) Alkylamino, tri (C_1-6) Alkyl ammonium, (C_1-6) Alkyloxy, (C_1-6) Alkyloxycal Bonil, (C_1-6) Alkanoyloxy, amino, carboxy, carbamoyl, (C_1-6) Alkylcarbamoyl, di (C_1-6) Alkylcarbamoyl, halo, and And optionally substituted by one or three substituents selected from hydroxy Often;   R₁Is amino (N_1-4) Azolidinyl, amino (N_1-4) Azolyl, (N_1-4A) Zolidinyl, (N_1-4) Azolyl, carbamoyl, cyano,-(CH_Two)_xNHC (NR⁹) R⁹ , − (CH_Two)_xNHC (NH) NR⁹R⁹, −C (NR⁹) R⁹, −C (NH) NHR^Ten, −C (NH) N^TenR^TenOr-(CR¹¹ R¹¹)_yNH_TwoAnd any ring having an available valence constituting B Attached to an atom, wherein x is 0 or 1 and y is 0, 1, 2, or 3, each R⁶Is independently hydrogen or (C_1-6) Alkyl, each R^Ten Are independently (C_1-6) Is alkyl and each R¹¹Is independently hydrogen or (C_1-3) Is alkyl or another R¹¹And the carbon source to which they are bound Together with the child to form cyclopropyl, where R¹Aliphatic or fat constituting The cyclic component is optionally (C_1-6) Alkyloxycarbonyl, (C_1-6) Arcanoy Ruoxy, carboxy, carbamoyl, (C_1-6) Alkylcarbamoyl, di ( C_1-6) Alkylcarbamoyl, (C_1-6) Alkylsulfonyl and hydroxy May be substituted with one or two substituents independently selected from:   Individual R^TwoAre independently (C_1-6) Alkyl, (C_1-6) Alkyloxycarbo Nil, (C_1-6) Alkanoyloxy, (C_1-6) Alkyloxy, carboxy, Carbamoyl, (C_1-6) Alkylcarbamoyl, di (C_1-6) Alkyl carbamo Il, (C_1-6) Alkylsulfinyl, (C_1-6) Alkylsulfonyl, (C_{1- 6} A) alkylthio, halo or hydroxy, and available to constitute B Attached to any valence ring atom, wherein R^TwoConstituents of aliphatic components Is optionally (C_1-6) Alkyloxycarbonyl, (C_1-6) Alkanoyloxy , Carboxy, carbamoyl, (C_1-6) Alkylcarbamoyl, di (C_1-6A) Lucilcarbamoyl, (C_1-6) Independent from alkylsulfonyl and hydroxy Optionally substituted by one or two substituents selected;   Individual R^ThreeAre independently (C_1-6) Alkyl, (C_1-6) Alkyloxy, (C_{1 -6} ) Alkylthio, cyano, halo, perhalo (C_1-6) Alkyl or hydroxy And is attached to any ring atom having an available valence constituting C Done; and   R^FourIs -R¹², −OR¹², −N (R¹³) R¹², −SR¹², −S (O) R¹², −S (O) _Two R¹², −S (O)_TwoOR¹², −S (O)_TwoN (R¹³) R¹², −N (R¹³) S (O)_TwoR¹², −C (O) R¹², −C (O) OR¹², −C (O) N (R¹³) R¹², −N (R¹³) C (O) R¹², −OC (O) N (R¹³) R¹², −N (R¹³) C (O) OR¹² , − (CH_Two)_zN (R¹³) C (O) N (R¹³) R¹², OP (O) (OR¹³) OR¹²Or -C (O) N (R¹⁴) CH (COOH) R¹²And for any ring atom of available valence constituting C Combined, where   z is 0, 1 or 2;   R¹²Is -R^FifteenOr -X⁶− (R^Fifteen)_n15Where n15 is 1 or 2 and X⁶Is (C_1-10) Alkylene, cyclo (C_3-10) Alkylene, hetero (C_2-10) Archi Len or heterocyclo (C_3-10A) alkylene and the individual R^FifteenIs independent And hydrogen, (C_6-14) Aryl, cyclo (C_3-14) Alkyl, polycyclo (C_{6- 14} ) Aryl, heteropolycyclo (C_6-14) Aryl, heterocyclo (C₃₁₄) Alkyl, hetero (C_5-14A) aryl or as defined below;   R¹³Is hydrogen, (C_1-6) Alkyl or hetero (C_2-6) Is alkyl;   R¹⁴Is hydrogen or (C_1-6) Is alkyl or X⁶And R^FifteenTogether with T (C_3-4) Forming an alkylene;   R^FourAny of the aliphatic and cycloaliphatic components that make up_1-6) Alkyl, (C_1-6 ) Alkylamino, di (C_1-6) Alkylamino, (C_1-6) Alkyl carba Moyle, di (C_1-6) Alkylcarbamoyl, (C_1-6) Alkyloxy, (C_{1- 6} ) Alkyloxycarbonyl, (C_1-6) Alkylsulfinyl, (C_1-6A) Rukylsulfonyl, (C_1-6) Alkylthio, amino, (C_6-10) Arylsul Honyl, carbamoyl, carboxy, cyano, guanidino, halo, hydroxy, Independently selected from Mercapto and Uried Optionally substituted with 1 to 5 substituents described above;   R^FifteenIs any of the aromatic components cyano, guanidino, halo, halo- Replaced (C_1-6) Alkyl, -R¹⁶, −OR¹⁶, −SR¹⁶, −S (O) R¹⁶, −S (O)_Two R¹⁶, −S (O)_TwoN (R¹³) R¹⁶, −C (O) R¹⁶, −C (O) OR¹⁶And -C (O) N (R^Fifteen) R¹⁶Independent from Optionally substituted with 1 to 3 substituents selected as described above, wherein R^Fifteen Is as defined above, and R¹⁶Is hydrogen, optionally monosubstituted (C_1-8) Alkyl) (where the optional substituent is (C_1-6) Alkylamino, di (C_1-6) Alkylamino, tri (C_1-6) Alkyl ammonium, (C_1-6) Al Kircarbamoyl, di (C_1-6) Alkylcarbamoyl, (C_1-6) Alkyl oxy Cycarbonyl, (C_1-6) Alkyloxysulfonyl, amino, carboxy, ka Rubamoyl, hydroxy or sulfo), cyclo (C_3-6) Alkyl, f Terrorism (C_1-8) Alkyl, hetero (C_3-6) Aryl, heterocyclo (C_3-6A) Alkyl or phenyl;   Provided that n2 is 0 or R^TwoIs (C_1-6) Alkyl or (C_1-6) Alkyl Oxy, n3 is 0, or^ThreeIs (C_1-6) Alkyl or (C_1-6A) Is alkyloxy and R^FourIs hydrogen, (C_1-10) Alkyl or (C_1-10A) N1 is not 0 when it is alkyloxy); -Oxide derivatives, prodrug derivatives, protected derivatives, individual isomers, Mixtures of the active ingredients, and pharmaceutically acceptable salts.   2. A contains 5 ring members and B contains 6 ring members, and X¹And X^Five Is oxazol-2-yl, 1H-imidazol-2-yl or thiazol-2 -A compound of formula I which is an adjacent member of the yl ring; and N-oxide derivatives thereof , Prodrug derivatives, protected derivatives, individual isomers, mixtures of isomers, and And pharmaceutically The compound of claim 1 which is an acceptable salt.   3. Formula II below: [Wherein the dotted lines may independently represent any bond;   Individual R^TwoAre independently (C_1-6) Alkyl, (C_1-6) Alkyloxy, halo Or hydroxy;   Individual R^ThreeAre independently (C_1-6) Alkyl, (C_1-6) Alkyloxy, halo Or hydroxy,   X^ThreeIs -C (O)-or -CR⁷R⁸-   X⁸Is --CH (R¹)_n1-Or -C (R¹)_n1= Where R¹Is amino (N_1-4A) Zolidinyl, amino (N_1-4) Azolyl, (N_1-4) Azolidinyl, (N_1-4) Azo Lil, -NHC (NH) NR⁹R⁹, −C (NR⁹) R⁹, −C (NH) NHR⁹, −C (NH) NR^TenR^TenOr-(CR¹¹ R¹¹)_yNH_TwoOr X⁸Is -N = or -NH (R¹)_n1-Where R¹Is- C (NR⁹) R⁹, −C (NH) NHR^TenOr -C (NH) NR^TenR^TenWhere each individual R⁹Is independent And hydrogen or (C_1-6) Is alkyl and each R^TenAre independently (C_1-6) Alkyl; and   X⁹Is --CH (R^Four)-Or -C (R^Four) =, Where R^FourIs -R¹², −OR¹², −N (R¹³) R¹², −SR¹², −S (O) R¹², −S (O)_TwoR¹², −S (O)_TwoOR¹², −S (O)_TwoN (R¹³) R¹², −N (R¹³ ) S (O)_TwoR¹², −C (O) R¹², −C (O) OR¹², −C (O) N (R¹³) R¹², −N (R¹³) C (O) R¹², − OC (O) N (R¹³) R¹², −N (R¹³) C (O) OR¹², − (CH_Two)_n4N (R¹³) C (O) N (R¹³) R¹², OP (O) (OR¹³ ) OR¹²Or -C (O) N (R¹⁴) CH (COOH) R¹²Or X⁹Is -N = or -N (R^Four) -Where R^FourIs -C (O) R¹², −C (O) OR¹², −C (O) N (R¹³) R¹², −OC (O) N (R^{1 Three} ) R¹²Or -C (O) N (R¹⁴) CH (COOH) R¹²Is a compound represented by the formula: 3. The compound according to item 2.   4. R^FiveIs hydrogen, or (C_1-4) Alkyl;⁶Is hydrogen or (C_1-4) Al And the alkyl is optionally (C_1-4) Alkyloxy, hydroxy and And 1 to 2 substituents independently selected from sulfo , R⁷Is hydrogen or methyl, and R⁸Is hydrogen, methyl or hydroxy ;   X⁸Is -C (R¹)_n1= Where R¹Is aminomethyl, 1-aminocyclopro Pill, 2-aminoimidazol-1-yl, 2-amino-1,1-dimethylethyl , Imidazolyl, tetrazolyl,-(CH_Two)_xNHC (NR⁹) R⁹, − (CH_Two)_xNHC (NH) NR⁹R⁹ And -C (NR^Five) R⁹Where each individual R⁹Is independently hydrogen or methyl; Or X⁸Is −N (R¹)_n1= Where R¹Is -C (NR⁹) R⁹, −C (NH) NHR^TenOr -C (NH) NR^TenR^TenWhere each individual R⁹Is independently hydrogen or methyl; and And individual R^TenIs methyl, where R¹Any of the aliphatic or alicyclic constituents of The formula component comprises one to two independently selected from methylsulfonyl and carboxy. May be substituted by a substituent;   X⁹Is -C (R^Four) =, Where R^FourIs -R¹², −OR¹², −C (O) R¹², −C (O) OR¹² , −C (O) N (R¹³) R¹²Or -C (O) N (R¹⁴) CH (COOH) R¹²Where R¹³And R¹⁴Is Independently, hydrogen or (C_1-6) Is alkyl;¹²Is -R^FifteenOr -X⁶− (R^Fifteen)_n15 Where X⁶Is (C_1-10) Alkylene or hetero (C_2-10) With alkylene Yes, and individual R^FifteenIs independently hydrogen, (C_6-14) Aryl, cyclo (C_{3- 14} ) Alkyl, polycyclo (C_6-14) Aryl, heterocyclo (C_3-14) Ally Or hetero (C_5-14) Is aryl;   R^FourIs any of the aliphatic or cycloaliphatic components_1-4) Alkyloxy , (C_1-4) Alkyloxycarbonyl, amino, carbamoyl, carboxy and And optionally substituted with 1 to 5 substituents independently selected from hydroxy May be; and   R^FifteenIs any of the aromatic components (C_1-4) Alkyl, (C_1-4) Al Killoxy, (C_1-4) Alkyloxycarbonyl, carbamoyl, carboxy , Cyano, cyclo (C_3-6) Alkyloxy, halo, hetero (C_1-8) Alkyl, Hetero (C_1-8) Alkylcarbonyl, hetero (C_5-6) Aryl and trifluoro Optionally substituted with 1 to 3 substituents independently selected from Compounds of formula I; and N-oxide derivatives, prodrug derivatives, protection thereof Derivatives, individual isomers, mixtures of isomers, and pharmaceutically acceptable salts. 4. The compound according to claim 3, wherein   5. A is combined with B to form 4,5,6,7-tetrahydro-1H-imidazo Constitutes [4,5-c] pyridin-2-yl, wherein n2 is 0 and R¹ Is -C (NR⁹) R⁹And R^FiveIs hydrogen, or A is with B 1H-benzimidazol-2-yl or 4,5,6,7-tetrahydro-1 Constitutes H-benzimidazol-2-yl, where R¹Is aminomethyl or Anidino and individual R¹Is independently halo, or hydroxy;   C is 4,5,6,7-tetrahydro-1H-imidazo [4,5-c] pyridi Or 1H-benzimidazol-2-yl, where R^FourIs −C (O) X⁶−R^Fifteen, −C (O) OX⁶−R^FifteenOr -C (O) NHX⁶−R^FifteenWhere X⁶Is (C_{1 -Four} ) Alkylene or hetero (C_2-4) Is alkylene and R^FifteenIs (C_6-10 ) Ally Le, (C_6-10) Aryloxy, polycyclo (C_6-10) Aryl, hetero (C_{Five- Ten} ) Aryl, hetero (C_5-10) Aryloxy or heteropolycyclo (C_6-14 ) Aryl; and   R^FifteenIs any of the aromatic components (C_1-4) Alkyl, (C_1-4) Al Killoxy, (C_1-4) Alkyloxycarbonyl, carboxy, carbamoyl , Halo, hydroxy, and tetrazol-1-yl, independently selected from A compound of formula I, optionally substituted with three substituents; Oxide derivatives, prodrug derivatives, protected derivatives, individual isomers, isomers 5. The compound according to claim 4, which is a mixture of the above and a pharmaceutically acceptable salt.   6. A together with B constitutes 1H-benzimidazol-2-yl And individual R^TwoIs independently halo or hydroxy; and the N- Oxide derivatives, prodrug derivatives, protected derivatives, individual isomers, isomers The compound according to claim 5, which is a mixture of a body and a pharmaceutically acceptable salt.   7. Compounds wherein n1 is 0; and N-oxide derivatives and prodrug derivatives thereof Isomers, protected derivatives, individual isomers, mixtures of isomers and pharmaceutically acceptable 7. The compound according to claim 6, which is a salt.   8. 2- (2- {2- [1- (4,6,7-trifluoro-1H-benzoimidyl) Dazol-2-yl) ethyl] 3-methyl-3H-benzimidazol-5-i Lecarbonylaminodiethoxy) benzoic acid;   2- (2- {2- [1- (5,6-difluoro-1H-benzimidazole- 2-yl) ethyl] 3-methyl-3H-benzimidazol-5-ylcarboni Ruaminodiethoxy) benzoic acid;   Butyl 2- (2- {2- [1- (5-hydroxy-1H-benzimidazole) -2-yl) ethyl] -3-methyl-3H-benzimidazol-5-ylcar Bonylaminodiethoxy) benzoate;   Propyl 2- (2- {2 = [1- (5-hydroxy-1H-benzimidazo) Ru-2-yl) ethyl] 3-methyl-3H-benzimidazol-5-ylcar Bonylaminodiethoxy) benzoate; and   Isobutyl 2- (2- {2- [1- (5 = hydroxy-1H-benzimidazo) 2-yl) ethyl] 3-methyl-3H-benzimidazol-5-dolphin A compound of formula I selected from rubornylaminodiethoxy) benzoate; These N-oxide derivatives, prodrug derivatives, protected derivatives, individual differences 8. The compound according to claim 7, which is a mixture of the isomers, isomers and pharmaceutically acceptable salts. Compound.   9. R¹Is guanidino or aminomethyl; and N-O Oxide derivatives, prodrug derivatives, individual isomers, mixtures of isomers, and pharmaceuticals 6. The compound according to claim 5, which is a chemically acceptable salt.   10.2- (5-guanidino-1H-benzimidazol-2-ylmethyl)- 3-methyl-N- (2-naphth-1-ylethyl) -3H-benzimidazole -5-carboxamide;   Ethyl 2- (3- {2- [1- (5-guanidino-1H-benzimidazole) -2-yl) ethyl] -1,4,6,7-tetrahydroimidazo [4,5-c] Pyridin-5-ylcarbonylaminodipropyl) benzoate;   2- (5-guanidino-1H-benzimidazol-2-ylme Tyl) -3- (2,3-dihydroxy) propyl-N- (2-naphth-1-yl Ethyl) -3H-benzimidazole-5-carboxamide;   2 (5-guanidino-1H-benzimidazol-2-ylcarbonyl) -3 -(2,3-dihydroxy) propyl-N- (2-naphth-1-ylethyl)- 3H-benzimidazole-5-carboxamide;   2 (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- ( 3-hydroxy) propyl-N- (2-naphth-1-ylethyl) -3H-ben Zoimidazole-5-carboxamide;   2- (5-guanidino-1H-benzimidazol-2-ylmethyl) -3- (2-hydroxy) ethyl-N- (2-naphth-1-ylethyl) -3H-ben Zoimidazole-5-carboxamide;   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -N- [2- (2-carbamoylphenoxy) ethyl] -3-methyl-3H- Benzimidazole-5-carboxamide;   2- [1- (5-guanidino-1H-benzimidazol-2-yl) ethyl ] -N- [2- (2-carbamoyl-4-chlorophenoxy) ethyl] -3-me Tyl-3H-benzimidazole-5-carboxamide;   4-chloro-2- [2-({2- [1- (5-guanidino-1H-benzoimid) Dazol-2-yl) ethyl] -3-methyl-3H-benzimidazol-5 Ylcarbonyl {amino) ethoxy] benzoic acid;   5-chloro-2- [2-({2- [1- (5-guanidino-1H-benziimi) Dazol-2-yl) ethyl] -3-methyl-3H- Benzimidazol-5-ylcarbonyl {amino) ethoxy] benzoic acid;   2- (5-aminomethyl-1H-benzimidazol-2-ylmethyl) -3 -Methyl-N- (2-naphth-1-ylethyl) -3H-benzimidazole- 5-carboxamide; and   2- (5-aminomethyl-4,5,6,7-tetrahydro-1H-benzoimid Dazol-2-ylmethyl) -3-methyl-N- (2-naphth-1-ylethyl A) a compound of formula I selected from -3H-benzimidazole-5-carboxamide And N-oxide derivatives, prodrug derivatives, and protected derivatives thereof , Individual isomers, mixtures of isomers and pharmaceutically acceptable salts. Item 9. The compound according to item 9, wherein   11． A together with B is 4,5,6,7-tetrahydro-1H-imidazo [4,5-c] pyridin-2-yl constitutes¹Is -C (NH) R⁷Is a compound And N-oxide derivatives, prodrug derivatives, protected derivatives, 6. The isomer, a mixture of isomers and a pharmaceutically acceptable salt. A compound as described.   12.2- [2- (2- {1- [5- (1-Iminoethyl) -4,5,6,7- Tetrahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl}- 3-methyl-3H-benzimidazol-5-ylcarbonylamino) ethoxy 〕benzoic acid;   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- (2-na Fut-1-ylethyl) -3H-benzimidazole-5-carboxamide;   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydrid B-1H-imidazo [4,5-c] pyridin-2-ylcarbonyl] -3-methyl Ru-N- (2-naphth-1-ylethyl) -3H-benzimidazole-5-ca Ruboxamide;   2- (5-iminomethyl-4,5,6,7-tetrahydro-1H-imidazo [ 4,5-c] pyridin-2-ylmethyl) -3-methyl-N- (2-naphth-1 -Ylethyl) -3H-benzimidazole-5-carboxamide;   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- (2-h Droxy-2-naphth-1-ylethyl) -3H-benzimidazole-5-ca Ruboxamide;   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- [2- ( 2-hydroxynaphth-1-yl) ethyl] -3H-benzimidazole-5 Carboxamide;   2- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H-i Midazo [4,5-c] pyridin-2-ylmethyl] -3-methyl-N- [2- ( 4-hydroxynaphth-1-yl) ethyl] -3H-benzimidazole-5 Carboxamide;   2- {1- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1 H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3-methyl-N- (2-Naphth-1-ylethyl) -3H-benzimidazole-5-carboxa Mid;   Ethyl 2- [2- (2- {1- [5- (1-iminoethyl) -4,5,6,7 -Tetrahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl -3-methyl-3H-benzimidazol-5-ylcarbonylamino) ethoxy B) benzoate;   2- [2- (2- {1- [5- (1-iminoethyl) -4,5,6,7-tetra] Lahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3- (2-methoxyethyl) -3H-benzimidazol-5-ylcarbonylamido G) ethoxy] benzoic acid;   Ethyl 2- [2- (2- {1- [5- (1-iminoethyl) -4,5,6,7 -Tetrahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl -1,4,6,7-tetrahydroimidazo [4,5-c] pyridin-5-dolphin Rubonylamino) ethoxy] benzoate; and   2 ｛1- [5- (1-Iminoethyl) -4,5,6,7-tetrahydro-1H -Imidazo [4,5-c] pyridin-2-yl] ethyl} -3-methyl-N- [ 2- (2-tetrazolylphenoxy) ethyl] -3H-benzimidazole-5 Compounds of formula I selected from carboxamides; and their N-oxide derivatives Isomers, prodrug derivatives, protected derivatives, individual isomers, mixtures of isomers, 12. The compound according to claim 11, which is a pharmaceutically acceptable salt.   13.2- [2- (2-｛-[5- (1-Iminoethyl) -4,5,6,7-te Trahydro-1H-imidazo [4,5-c] pyridin-2-yl] ethyl} -3 -Methyl-3H-benzimidazol-5-ylcarbonylamino) ethoxy] Benzoic acid; and its N-oxide derivative, prodrug derivative, protected derivative Isomers, individual isomers, mixtures of isomers and pharmaceutically acceptable salts. Item 12. The compound according to Item 12.   14. A compound according to claim 1 in combination with a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a substance.   15． Claims further comprising a β-adrenergic agonist compound Item 15. The pharmaceutical composition according to Item 14.   16． The β-adrenergic agonist compound may include albralol, ter Selected from the group consisting of butaline, formoterol, fenoterol and prenaline 15. The pharmaceutical composition according to claim 14, which is used.   17． Claims wherein the composition comprises a pharmaceutically acceptable topical carrier. Item 14. The pharmaceutical composition according to Item 14.   18． Claims wherein the composition comprises a pharmaceutically acceptable oral carrier. Item 14. The pharmaceutical composition according to Item 14.   19. The composition wherein the composition comprises a pharmaceutically acceptable aerosol carrier. 15. The pharmaceutical composition according to claim 14, wherein   20. Claim 1 in a pharmaceutically acceptable carrier solution or dry powder. The compound of claim 5, and said solution or powder is in an aerosol form suitable for inhalation. An aerosol device comprising means for converting.   twenty one. A method for treating an immune-mediated inflammatory disease in a mammal, comprising the steps of: Administering to the mammal a therapeutically effective amount of the compound of claim 1. Method consisting of:   twenty two. A method for treating rheumatoid arthritis in a mammal, comprising the steps of claim Comprising administering to said mammal a therapeutically effective amount of a compound according to claim 1. Way.   twenty three. A method for treating conjunctivitis in a mammal, comprising the steps of claim 1. A method comprising administering to the mammal a therapeutically effective amount of the described compound.   twenty four. A method for treating syncytial virus infection in a mammal, comprising: Administering a therapeutically effective amount of the compound of claim 1 to said mammal. Comprising a method.   twenty five. For treating immune-mediated inflammatory diseases of the mammalian respiratory tract A method of administering to a mammal a therapeutically effective amount of a compound as defined in claim 1. A method comprising providing.   26. Formula I below: Wherein n1 is 0 or 1;   n2 is 0, 1, 2, 3, or 4;   n3 is 0, 1, 2, 3, or 4;   A together with B forms a fused heterobicyclic group containing from 8 to 12 ring atoms. Wherein each ring is from 5 to 7 ring members and each ring atom is optionally hetero Can be an atom, X¹And X^TwoIs an adjacent ring member of an aromatic ring;¹ Is a heteroatom component selected from -N =, -O-, and -S-;¹as well as X^TwoIs oxazol-2-yl, 1H-imidazol-2-yl or thiazole -2-yl is an adjacent ring member of the 1H-imidazol-2-yl ring Ring member is -NR^Five−, Where R^FiveIs hydrogen, (C_1-6) Alkyl or hete B (C_2-4) Is alkyl;   C constitutes a fused heteropolycyclic group containing from 8 to 18 ring atoms and any of Comprising carbocyclic ketone, thioketone and imino ketone derivatives, where Contains from 5 to 7 ring members, and each ring atom may optionally be a heteroatom. Yes, X^FiveIs a heteroatom component selected from -N-, -O- and -S-; And X^FourAnd X^FiveIs oxazol-2-yl, 1H-imidazol-2-yl Or an adjacent ring member of a thiazol-2-yl ring, wherein 1H -The ring member of the imidazol-2-yl ring is -NR⁶-Where R⁶Is hydrogen, (C_{1- 6} ) Alkyl or hetero (C_2-12A group selected from the group consisting of (C)_{1 -6} ) Alkanoyloxy, (C_1-6) Alkylamino, di (C_1-6) Alkylam No, bird (C_1-6) Alkyl ammonium, (C_1-6) Alkylcarbamoyl, di ( C_1-6) Alkylcarbamoyl, (C_1-6) Alkyloxy, (C_1-6) Alkyl Oxycarbonyl, (C_1-6) Alkyloxysulfonyl, amino, carboxy , Carbamoyl, (C_6-14) Aryl, halo, hetero (C_5-14) Aryl, Hyd Optionally substituted by one or two substituents independently selected from roxy and sulfo Or as defined below;   X^ThreeIs -O-, -S-, -S (O)-, -S (O)_Two−, −C (O) −, −NR⁷-Or -CR⁷R⁸ -Where R⁷Is hydrogen, (C_1-6) Alkyl or hetero (C_2-12) Al Kill or R⁶Together with (C_2-4) Alkylene is hetero (C_2-4A) Forming alkylene; and R⁸Is hydrogen, (C_1-6) With alkyl or hydroxy Yes or R⁷Together with (C_2-6) Alkylene or (C_1-6) Alkylidene Where R⁷And / or R⁸Any aliphatic or cycloaliphatic component that constitutes Is (C_1-6) Alkylamino, di (C_1-6) Alkylamino, tri (C_1-6A) Lucir Ammonio, (C_1-6) Alkyloxy, (C_1-6) Alkyloxycarbo Nil, (C_1-6) Alkanoyloxy, amino, carboxy, carbamoyl, ( C_1-6) Alkylcarbamoyl, di (C_1-6) Alkylcarbamoyl, halo, and Optionally substituted with one or three substituents selected from hydroxy. ;   R₁Is amino (N_1-4) Azolidinyl, amino (N_1-4) Azolyl, (N_1-4A) Zolidinyl, (N_1-4) Azolyl, carbamoyl , Cyano,-(CH_Two)_xNHC (NR⁹) R⁹, − (CH_Two)_xNHC (NH) NR⁹R⁹, −C (NR⁹) R⁹, −C (NH) N HR^Ten, −C (NH) NR^TenR^TenOr-(CR¹¹R¹¹)_yNH_TwoAnd in the uses that make up B Attached to any ring atom having the following valencies, wherein x is 0 or 1, y is 0, 1, 2, or 3;⁹Is independently hydrogen or (C_1-4) Archi And the individual R^TenAre independently (C_1-6) Is alkyl and each R¹¹ Is independently hydrogen or (C_1-3) Is alkyl or another R¹¹And both Together with the carbon atom to which it is attached forms cyclopropyl, where R¹To The constituent aliphatic or cycloaliphatic component is optionally (C_1-6) Alkyloxycarbonyl , (C_1-6) Alkanoyloxy, carboxy, carbamoyl, (C_1-6) Archi Rucarbamoyl, di (C_1-6) Alkylcarbamoyl, (C_1-6) Alkylsulfo Substituted by one or two substituents independently selected from nil and hydroxy May be   Individual R^TwoAre independently (C_1-6) Alkyl, (C_1-6) Alkyloxycarbo Nil, (C_1-6) Alkanoyloxy, (C_1-6) Alkyloxy, carboxy, Carbamoyl, (C_1-6) Alkylcarbamoyl, di (C_1-6) Alkyl carbamo Il, (C_1-6) Alkylsulfinyl, (C_1-6) Alkylsulfonyl, (C_{1- 6} A) alkylthio, halo or hydroxy, and available to constitute B Attached to any valence ring atom, wherein R^TwoConstituents of aliphatic components Is optionally (C_1-6) Alkyloxycarbonyl, (C_1-6) Alkanoyloxy , Carboxy, carbamoyl, (C_1-6) Alkylcarbamoyl, di (C_1-6A) Lucilcarbamoyl, (C_1-6) Independent from alkylsulfonyl and hydroxy Optionally substituted by one or two substituents selected;   Individual R^ThreeAre independently (C_1-6) Alkyl, (C_1-6) Archi Luoxy, (C_1-6) Alkylthio, cyano, halo, perhalo (C_1-6) Alkyl Or hydroxy and having an available valence constituting C Attached to any of the ring atoms; and   R^FourIs -R¹², −OR¹², −N (R¹³) R¹², −SR¹², −S (O) R¹², −S (O)_TwoR¹², −S (O)_Two OR¹², −S (O)_TwoN (R¹³) R¹², −N (R¹³) S (O)_TwoR¹², −C (O) R¹², −C (O) OR¹², −C (O) N (R¹³) R¹², −N (R¹³) C (O) R¹², −OC (O) N (R¹³) R¹², −N (R¹³) C (O) OR¹², − (CH_Two)_z N (R¹³) C (O) N (R¹³) R¹², OP (O) (OR¹³) OR¹²Or -C (O) N (R¹⁴) CH (COOH) R¹²And And is attached to any of the available valence ring atoms that constitute C; Here   z is 0, 1 or 2;   R¹²Is -R^FifteenOr -X⁶− (R^Fifteen)_n15Where n15 is 1 or 2 and X⁶Is (C_1-10) Alkylene, cyclo (C_3-10) Alkylene, hetero (C_2-10) Archi Len or heterocyclo (C_3-10A) alkylene and the individual R^FifteenIs independent And hydrogen, (C_6-14) Aryl, cyclo (C_3-14) Alkyl, polycyclo (C_{6- 14} ) Aryl, heteropolycyclo (C_6-14) Aryl, heterocyclo (C_3-14) Alkyl, hetero (C_5-14A) aryl or as defined below;   R¹³Is hydrogen, (C_1-6) Alkyl or hetero (C_2-6) Is alkyl;   R¹⁴Is hydrogen or (C_1-6) Is alkyl or X⁶And R^FifteenTogether with T (C_3-4) Forming an alkylene;   R^FourAny of the aliphatic and cycloaliphatic components that make up_1-6) Alkyl, (C_1-6 ) Alkylamino, di (C_1-6) Alkylamino, (C_1-6) Alkyl carba Moyle, di (C_1-6) Alkylcarbamoyl, (C_1-6) Alkyloxy, (C_{1- 6} ) Alkyloxy Carbonyl, (C_1-6) Alkylsulfinyl, (C_1-6) Alkylsulfonyl, (C_1-6) Alkylthio, amino, (C_6-10) Arylsulfonyl, carbamoy Carboxy, cyano, guanidino, halo, hydroxy, mercapto, and Optionally substituted with 1-5 substituents independently selected from Riedo;   R^FifteenIs any of the aromatic components cyano, guanidino, halo, halo- Replaced (C_1-8) Alkyl, -R¹⁶, −OR¹⁶, −SR¹⁶, −S (O) R¹⁶, −S (O)_Two R¹⁶, −S (O)_TwoN (R¹³) R¹⁶, −C (O) R¹⁶, −C (O) OR¹⁶And -C (O) N (R^Fifteen) R¹⁶Independent from Optionally substituted with 1 to 3 substituents selected as described above, wherein R^Fifteen Is as defined above, and R¹⁶Is hydrogen, optionally monosubstituted (C_1-8 ) Alkyl) (where the optional substituent is (C_1-6) Alkylamino, di (C_1-6) Alkylamino, tri (C_1-6) Alkyl ammonium, (C_1-6) Alkyl carba Moyle, di (C_1-6) Alkylcarbamoyl, (C_1-6) Alkyloxycarboni Le, (C_1-6) Alkyloxysulfonyl, amino, carboxy, carbamoyl , Hydroxy, or sulfo), cyclo (C_3-6) Alkyl, hetero (C_1-8 ) Alkyl, hetero (C_3-6) Aryl, heterocyclo (C_3-6) Alkyl or Enyl;   Provided that n2 is 0 or R^TwoIs (C_1-6) Alkyl or (C_1-6) Alkyl Oxy, n3 is 0, or^ThreeIs (C_1-6) Alkyl or (C_1-6A) Is alkyloxy and R^FourIs hydrogen, (C_1-10) Aryl or (C_1-10A) N1 is not 0 when it is reeloxy); N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers, A process for preparing a mixture of isomers, and a pharmaceutically acceptable salt,   (A) Formula 1: Wherein L is a leaving group and n1, n2, A, B, X¹, X^Two, X^Three, R¹, And R^TwoIs as defined above), or a protected compound thereof. And a derivative of formula 2:Wherein D is 5-15 ring atoms together with the vinylene moiety to which it is fused A monocyclic or fused bicyclic divalent group comprising: wherein each ring is from 5 to 7 rings Atoms and individual ring atoms can optionally be heteroatoms;²⁹ Is -OH, -NHR⁶Or -SH, where R⁶Is hydrogen, or (C_1-8) Alkyl Is hetero (C_2-12) A group selected from alkyl, wherein said group is optionally (C_{1- 6} ) Alkanoyloxy, (C_1-6) Alkylamino, di (C_1-6) Alkylam No, bird (C_1-6) Alkyl ammonium, (C_1-6) Alkylcarbamoyl, di ( C_1-6) Alkylcarbamoyl, (C_1-6) Alkyloxy, (C_1-10) Alkyl Oxycarbonyl, (C_1-6) Alkyloxysulfonyl, amino, carboxy , Carbamoyl, (C_6-14) Aryl, halo, hetero (C_5-14) Aryl, Hyd 1-2 substitutions independently selected from roxy and sulfo And n3, R3^Three, R^FourIs as above] Reacting with the compound represented, or a protected derivative thereof; Deprotect if necessary; or   (B) Formula 3 below: Wherein L is a leaving group and C, n3, X^Three, X^Five, R^ThreeAnd R^FourIs determined above And a protected derivative thereof represented by the following formula: 4:[Wherein, R³⁰Is -OH, -NHR^FiveOr -SH, and n1, n2, B, R¹, R^Two And R^FiveIs as defined above) or a protected compound thereof Reacting with the derivative and, if necessary, deprotecting;   (C) optionally further converting the compound of formula I to a pharmaceutically acceptable salt;   (D) optionally further converting the salt form of the compound of formula I to a non-salt form;   (E) optionally further comprises the pharmaceutically acceptable unoxidized form of the compound of formula I To an acceptable N-oxide;   (F) optionally further comprising converting the N-oxide form of the compound of formula I to its oxidized form. Conversion to a non-existent form;   (G) Optionally, further, the non-derivatized compound of the compound of formula I is pharmaceutically acceptable. To a prodrug derivative; and   (H) optionally further comprising converting the compound of formula I to a non-derived A method comprising converting to a body shape.