Field of the Invention
Provided herein are substituted aromatic compounds, which are tRNA, synthetase inhibitors, and hence can be used as antimicrobial agents. Compounds disclosed herein can be used for the treatment or prevention of a condition caused by or contributed to by gram positive, gram negative, anaerobic bacteria or fungal organisms, more particularly against bacterium, for example, Staphylococci, Enterococci, Streptococci, Haemophilus, Moraxalla, Escherichia, Chlamydia, Rickettsiae, Mycoplasm, Legionella, Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae, and fungal organisms, for example, Aspergillus, Blastomyces, Candida, Coccidiodes, Cryptococcus, Epidermophyton, Hendersonula, Histoplasma, Microsporum, Paecilomyces, Paracoccidiodes, Pneumocystis, Trichophyton, or Trichosporium. Processes for the preparation of these compounds, pharmaceutical compositions thereof, and method of treating microbial infections are also provided.
Background of the Invention
Antibiotics are of immense value for combating infectious diseases. In recent decades,
the effectiveness of antibiotics has been threatened by an inexorable rise in the prevalence of
microbial drug resistance. Some important pathogens have se'rious resistance problems.
Staphylococcus aureus is perhaps the most significant of these pathogens. It causes community and hospital acquired infections and is associated with high morbidity and mortality rates. Vancomycin has been used as the antibiotic of last resort to treat methicillin-resistance Staphylococcus aureus infections (MRSA) with multiple resistance. Strains with some level of resistance to vancomycin (Vancomycin-intermediates-resistant S. aureus, VISA) have been known since 1996, but the newly identified highly resistant strain (VRSA) heralds a new stage in the battle with this pathogen. Other serious treatment problems include multidrug resistance in tuberculosis, vancomycin resistant enterococci (VRE), resistance owing to extended spectrum p-lactamases (ESBLs) in Enterobacteriaceae and Pseudomonas aeruginosa, and penicillin resistance in Streptococcus pneumonias.
A nation wide epidemic of multi drug resistant Salmonella typhi occurred in 1990 and has not yet fully subsided. Antimicrobial resistance among respiratory pathogens has become a common clinical problem; currently over 90% of Morexella catarrhalis and 25% of Haemophilus influenzae produce [3 lactamases, requiring treatment with a P lactamase stable cephalosporin or combination drugs. In the last several years, there has been a rapid increase in the number of strains resistant to penicillin, cephalosporins, macrolides and fluoroquinolones.
These circumstances have prompted efforts to develop new antibiotics that overcome the emerging antibiotic resistance bacteria. The amino acyl tRNA synthetases are essential enzymes found in all living organisms. These enzymes have emerged as an attractive target for the development of new antibiotics. Amino acyl tRNA synthetases charge tRNA molecules with their corresponding amino acid, an essential step in protein synthesis. There are 20 tRNA synthetases, most of which correspond to attractive broad-spectrum antibacterial targets. This is a validated target class in that pseudomonic acid A, also known as mupirocin, a natural product from Pseudominas fluorescens, inhibits isoleucyl tRNA synthtase and is marketed as a topical antibiotic Bactropan. Other known natural products directed against amino acyl tRNA synthetases include borrelidin, furanomycin, granaticin, indolmycin, ochartoxin A, and cispentacin; none of them has been developed as antibiotic compounds.
U.S. Patent Application Nos. 20040224981 and 20030013724 disclose tRNA synthetase inhibitors. WO 00/18772 discloses condensed imidazolidinone as tRNA synthetase inhibitors. U.S. Patent Nos. 5,191,093 and 4,916,155 disclose crystalline pseudomonate, process for its production and its use in human and veterinary medicines. U.S. Patent No. 4,916,155 discloses crystalline calcium pseudomonate or the hydrate thereof, and their use in human and veterinary medicine.
Novel synthetic compounds, which target tRNA synthetases, offer clear advantages as useful therapeutic agents to curb the threat of drug resistance.
Summary of the Invention
Accordingly, this invention provides substituted aromatic compounds, which are tRNA synthetase inhibitors, and hence can be used for the treatment of microbial infections, and processes for the synthesis of these compounds. Pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs, metabolites, polymorphs and N-oxides of these compounds having same type of activity are also provided. Pharmaceutical compositions containing the disclosed compounds (Formula I) together with pharmaceutically acceptable carriers, excipients or diluents, which can be used for the treatment of microbial infections. Other aspects will be set forth in the accompanying description which follows and in part will be apparent from the description or may be learnt by the practice of the invention.
In one aspect, provided herein are compounds having the structure of Formula I,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy can be cyclopentyl or cyclohexyl; X can be CH2C(CH3) or CH(OH)C(CH3); Z can be CH2; Y can be NH or NSO2CH3; X, can be CH or N; R can be NR]R2 [wherein R, and R2 can be independently hydrogen, SO2R3, COR3, CONHR3, CONHSO2R3 or COOCH2R3 (wherein R3 can be N(CH3)2, NH2, CH=CHCOOC2H5, (CH2)3COOC2H5, phenyl, 1,2,3,4-tetrahydroisoquinolinyl, 2,2,2-trifluoacetyl-l-(3,4-dihydro-lH-isoquinolin-2-yl), morpholinyl or heteroaryl)].
In a second aspect, provided herein is a method for treating or preventing a subject suffering from a condition caused by or contributed to by gram positive, gram negative, anaerobic bacteria or fungal organisms, comprising administering to said subject, a therapeutical ly effective amount of a compound or a pharmaceutical composition disclosed herein.
Bacterium, for example, Staphylococci, Enterococci, Streptococci, Haemophilus, Moraxalla, Escherichia, Chlamydia, Rickettsiae, Mycoplasm, Legionella, Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae may cause the bacterial infections.
Organisms, for example, Aspergillus, Blastomyces, Candida, Coccidiodes, Cryptococcus, Epidermophyton, Hendersonula, Histoplasma, Microsporum, Paecilomyces, Paracoccidiodes, Pneumocystis, Trichophyton, or Trichosporium, Enterobactericeae may cause the fungal infections.
The conditions may be, for example, community acquired pneumonia, upper and lower respiratory tract infections, skin and soft tissue infections, hospital acquired lung infections or bone and joint infections, and other bacterial infections, for example, mastitis, catheter infection, foreign body, prosthesis infections or peptic ulcer disease.
In a third aspect, there are provided processes for the preparation of compounds as disclosed herein.
The following definitions apply to terms as used herein:
Heteroaryl as used herein can be pyrazolyl, imidazolyl, thienyl, isoxazolyl, pyridinyl, isoquinolinyl, benzoisoxazolyl, benzothienyl, benzothiazolyl, bemzimidazolyl, pyrazolyl-3-one or thiazolyl.
The group "heteroary" can optionally be substituted with substituent(s) selected from Cl, CH3, OCH3, NHCOCH3, NHCOOCH3, C6H4COOC2H5, SO2thienyl, furanyl, phenyl, thienyl, trimethoxyphenyl, pyrazinyl or isoxazolyl.
The group "phenyl" can optionally be substituted with substituent(s) selected from Cl, Br, NH2, OCH3, CONH2, NHCOCH3, CH(OH)CH3, C(CH3)=NOH, C(CH3)=NOCH3, NH-N(=NH)NH2, oxazolyl, pyrrolyl, pyrazolyl, pyridinyl, morpholinyl, pyrimidinyl, triazinyl, N-methyl-pyrazolyl, 2-oxo-oxazolidinyl, isoindolyl-l,3-dione, thiadiazolyl, pyrrolyl-3-carbaldehyde oxime, pyrrolyl-3-carbaldehyde, NHSO2R5 orNHCOR6 [(wherein R5 can be selected from C1-C4 alkyl, thienyl, 3,5-dimethyl-isooxazolyl, N-methyl-imidazolyl, p-acetylphenyl, 2,4-dimethyl-thiazolyl, 5-chloro-l,3-dimethyl-pyrazolyl, 2,5-dimethyl-furan-3-carboxylic acid methyl ester, 3-methyl-thiophene-2-carboxylic acid methyl ester, furan-2-carboxylic acid methyl ester, l-(3,4-dihydro-lH-isoquinolin-2-yl)-2,2,2-trifluoroethanone, indole-2-yl-carbamic acid methyl ester or phenylcarbaldehyde oxime), Re can be methyl, (CH2)3COOC2H5, NHC(CH3)2 or isoxazolyl)].
The term "pharmaceutically acceptable solvates" refers to solvates with either water (e.g., hydrates, hemihydrate or sesquihydrate), or pharmaceutically acceptable solvents, for example solvates with common organic solvents as ethanol and the like. Such solvates are also encompassed within the scope of the disclosure.
The present invention also includes within its scope prodrugs of these agents. In general, such prodrugs will be functional derivatives of these compounds, which are readily convertible in vivo into the required compound. Conventional procedure for the selection and preparation of suitable prodrug derivatives are described, for example, in "Design of Prodrugs", ed. H Bundgaard and, Elsevier, 1985. As used herein the term "prodrugs" refers to the compounds that are rapidly transformed in vivo to yield the parent compound of Formula I, for example by hydrolysis in blood.
The disclosed compounds may get metabolized in vivo and these metabolites are also encompassed within the scope of this invention.
The term "polymorphs" includes all crystalline form as well as amorphous forms for compounds described herein and as such are included in the present invention.
The phrase "pharmaceutically acceptable carriers" is intended to include non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type.
The term "pharmaceutically acceptable salts" refer to a salt prepared from pharmaceutically acceptable monovalent, divalent or trivalent non-toxic metal or organic base. Examples of such metal salts include, but are not limited to, lithium, sodium, potassium, calcium, magnesium, zinc, aluminum and the like. Examples of such organic bases include, but are not limited to, amino acid, ammonia, mono-alkyl ammonium, dialkyl ammonium, trialkyl ammonium and N-methyl glucamine and the like. The free acid forms of compounds of the present invention may be prepared from the salt forms, if desired, by contacting the salt with dilute aqueous solution of an acid, such as hydrochloric acid. The base addition salts may differ from the free acid forms of the compounds of this invention in such physical characteristics as solubility and melting point.
The term "pharmaceutically acceptable salts" can further refer to salts prepared from pharmaceutically acceptable non-toxic inorganic or organic acids. Examples of such inorganic acids include, but are not limited to, hydrochloric, hydrobromic, hydroiodic, nitrous, nitric, carbonic, sulfuric, phosphoric acid, and the like. Appropriate organic acids include, but are not limited to aliphatic, cycloaliphatic, aromatic, heterocyclic, carboxylic and sulfonic classes of organic acids, for example, formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic, methanesulfonic, ethanesulfonic, benzenesulfonic, panthenic, toluenesulfonic, 2-hydroxyethanesulfonic acid and the like.
The compounds of present invention include stereoisomers. The term "stereoisomer" refers to compounds, which have identical chemical composition, but differ with regard to arrangement of the atoms and the groups in space. These include enantiomers, diastereomers, geometrical isomers, atropisomer and conformational isomers as defined by the IUPAC 1974 Recommendations for Section E. All these stereoisomers are included within the scope of this invention.
The term "subject" as used herein refers to human or lower mammal.
The term "treatment", as used herein, unless otherwise indicated, includes the treatment or prevention of a bacterial or fungal infection as provided in the method of the present invention.
The term "pharmaceutically acceptable" means approved by regulatory agency of the federal or a state government or listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly in humans.
Detailed Description of the Invention
The compounds disclosed herein may be prepared by techniques well known in the art and familiar to the average synthetic organic chemist. In addition, the compounds of the present invention may be prepared by the following reaction sequences as depicted in Schemes I, la, Ib,
II, III, IV, V, VI and VII.
Scheme I
(Scheme Removed)
Sulfonamides of Formula 5 can be prepared according to Scheme I. Thus, compounds of Formula 2 can be reacted with compounds of Formula 3 to give compounds of Formula 4. Compounds of Formula 4 can be oxidized to give sulfonamides of Formula 5 (wherein X] and RS are the same as defined earlier).
Compounds of Formula 2 can be reacted in one or more organic bases, for example, pyridine, triethylamine, trimethylamine, tributylamine, 4-N-dimethylaminopyridine or Haning's base. Compounds of Formula 4 can be oxidized in the presence of one or more oxidizing agents, for example, Dess-Martin periodinane, 2-iodoxybenzoic acid, N-chloro succinimide, pyridinium chlorochromate, Swern Oxidation reagent (oxalyl chloride and dimethylsulfoxide), Pfitzner-Moffatt Oxidation reagent (dicyclohexylcarbodiimide and dimethylsulfoxide), Jones Oxidation reagent (chromic acid, aqueous sulfuric acid and acetone), pyridinium dichromate, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride or imixture thereof, in one or more solvents, for example, chlorinated solvents (e.g. chloroform, dichloromethane, carbon tetrachloride or dichloroethane), polar aprotic solvents (e.g. dimethylsulfoxide or dimethylformamide), ketones (e.g. dimethylketone, diethylketone or ethylmethylketone), nitriles (e.g. acetonitrile or propionitrile), ethers (e.g. diethyl ether, tetrahydrofuran or dioxane) or a mixture thereof. N-chlorosuccinamide can be used in combination with dimethyl sulphide and 1-ethyl-3(3-dimethylaminopropyl) carbodiimide hydrochloride can be used in combination with
dimethylsulfoxide.
Scheme la
(Scheme Removed)
Compounds of Formula 9 can be prepared according to Scheme la. Thus, compounds of Formula 6 can be reacted with compounds of Formula R3COOH to give compounds of Formula 7 (wherein R4 is a protecting group, for example, tert-butyldimethylsilyl, trimethylsilyl, 4-benzyloxybutyryl, l,4-diazabicyclo[2.2.1]octane or tert-butyldiphenylsilyl). Compounds of Formula 7 can be deprotected to give compounds of Formula 8. Compounds of Formula 8 can be oxidized to give compounds of Formula 9 (wherein X] and R3 are the same as defined earlier).
Compounds of Formula 6 can be in the presence of one or coupling agents, for example, 1-hydroxybenzotriazole, l-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimodazole orN,N'-carbonyldiimidazole, in one or more aprotic solvents, for example, N-methyl-2-pyrrolidinone, dimethylformamide or dimethylformamide. Compounds of Formula 7 can be deprotected in the presence of tetra-n-butylammonium fluoride, in one or more solvents, for example, ethers (e.g. tetrahydrofuran, dioxane or diethylether), aprotic solvents (e.g. dimethylsulfoxide or dimethylformamide), ketones (e.g. dimethylketone, diethylketone or ethylmethylketone) or mixture thereof. Compounds of Formula 8 can be oxidized using the
procedures described above.
Scheme Ib
(Scheme Removed)
Compounds of Formula 13 can be prepared according to Scheme Ib. Thus, compounds of Formula 6 can be reacted with imidazole to give compounds of Formula 10. Compounds of Formula 10 can be treated with compounds of Formula R3CH2OH to give compounds of
Formula 11 (wherein R4 is a protecting group, for example, tert-butyldimethylsilyl, trimethylsilyl, 4-benzyloxybutyryl, l,4-diazabicyclo[2.2.1]octane or tert-butyldiphenylsilyl). Compounds of Formula 11 can be deprotected to give compounds of Formula 12. Compounds of Formula 12 can be oxidized to give compounds of Formula 13 (wherein Xi and RS are the same as defined earlier).
Compounds of Formula 6 can be reacted in the presence of one or more coupling agents, for example, N,N-carbonyldiimidazole, N,N-dithiocarbonyldiimidazole, N,N-dicyclohexylcarbodiimide or l-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride in one or more solvents, for example, chlorinated solvent (e.g. chloroform, dichloromethane, dichloroethane or tetrachloromethane), polar aprotic solvents (e.g. dimethylformamide or dimethylsuloxide), ketones (e.g. dimethylketone, diethylketone or ethylmethylketone), ethers (e.g. diethylether, tetrahydrofuran or dioxane) or mixture thereof. Compounds of Formula 10 can be treated in one or more solvents, for example, chlorinated solvent (e.g. dichloromethane, dichloroethane, chloroform or tetrachloromethane), aprotic solvents (e.g. dimethylformamide or dimethylsulfoxide), nitrites (e.g.acetonitrile or propionitrile), ethers (e.g. diethylether, tetrahydrofuran or dioxane) or mixture thereof. Compounds of Formula 11 can be deprotected in the presence of tetra-n-butylammonium fluoride in one or more solvents, for example, ethers (e.g. tetrahydrofuran, dioxane or ether), polar aprotic solvents (e.g. dimethylsulfoxide or dimethylformamide), ketones (e.g. dimethylketone, diethylketone or ethylmethylketone) or mixture thereof. Compounds of Formula 12 can be oxidized using the procedures described above.
Scheme II
(Scheme Removed)
Compounds of Formula 19 can be prepared according to Scheme II. Thus, L-alaniol of Formula 14 can be reacted with di-tert-butyldicarbonate of Formula 15 to give (2-hydroxy-l-methylethyl)-carbamic acid tert-butyl ester of Formula 16. Compound of Formula 16 can be treated with tosyl chloride to give 2-methyl-aziridine-l-carboxylic acid tert-butyl ester of Formula 17. Compound of Formula 17 can be reacted with compounds of Formula Cy-Ha to
give compounds of Formula 18 (wherein Ha is halogen). Compounds of Formula 18 can be deprotected to give compounds of Formula 19 (wherein Cy is the same as defined earlier).
2-amino-propan-l-ol of Formula 14 can be reacted in one or more solvents, for example, chlorinated solvent (e.g. chloroform, dichloromethane, carbon tetrachloride or dichloroethane), polar aprotic solvent (e.g. dimethylsulfoxide or dimethylformamide), nitriles (e.g. acetonitrile or propionitrile), ethers (e.g. diethylether, tetrahydrofuran or dioxane) or mixture thereof. (2-hydroxy-l-methylethyl)-carbamic acid tert-butyl ester of Formula 16 can be raected in one or more solvents, for example, ethers (e.g. diethylether, dioxane or tetrahydrofuran), chlorinated solvents (e.g. dichloromethane, dichloroethane, carbon tetrachloride or chloroform) or mixture thereof. Compound of Formula 16 can also be reacted in the presence of one or more inorganic bases, for example, sodium hydride, potassium hydroxide, sodium hydroxide or calcium hydroxide. 2-methyl-aziridine-l-carboxylic acid tert-butyl ester of Formula 17 can be reacted in the presence of magnesium (in dry ether) in one or more solvents, for example, ethers (e.g. diethylether, dioxane or tetrahydrofuran), chlorinated solvents (e.g. dichloromethane or chloroform) or mixture thereof. Compounds of Formula 18 can be deprotected in the presence of one or more mineral acids, for example, trifluoroacetic, hydrochloric, hydrobromic or hydroiodic acid in one or more polar protic solvents, for example, water, methanol, ethanol, propanol, isopropanol or tert-butanol.
Scheme III
(Scheme Removed)
Compounds of Formula 20 can be prepared according to Scheme III. Thus, compounds of Formula 5 can be reacted with compounds of Formula 19 to give compounds of Formula 20 (wherein Cy, X1 and R3 are the same as defined earlier).
Compounds of Formula 5 can be reacted in the presence of one or more reducing agents, for example, sodium cyanoborohydride, sodium borohydride or sodium triacetoxyborohydride in one or more solvents, for example, polar protic solvents (e.g. methanol, ethanol, propanol, isopropanol or water), ethers (tetrahydrofuran, diethylether or dioxane) or mixture thereof.
Scheme IV (Scheme Removed)

Compounds of Formula 21 can be prepared according to Scheme IV using the procedures described in Scheme III.
Scheme V (Scheme Removed)

Compounds13 of Formula 22 can be prepared according to Scheme V using the procedure
described in Scheme III.
Scheme VI
(Scheme Removed)
Compounds of Formula 25 can be prepared according to Scheme VI. Thus, Compounds of Formula 23 can be reacted with compounds of Formula 3 (R3SO2Cl) to give compounds of Formula 24. Compounds of Formula 24 can be deprotected to give compounds of Formula 25 (wherein Cy, R3 and X1 are the same as defined earlier).
Compounds of Formula 23 can be reacted in the presence of one or more organic bases, for example, pyridine, triethylamine, trimethylamine, 4-N-methylaminopyridine or Haning's base. Compounds of Formula 24 can be deprotected in the presence of one or more mineral acids, for example, trifluoro, hydrochloric, hydrobromic or hydroiodic acid in one or more polar protic solvents, for example, methanol, ethanol, propanol, isopropanol or water.
Scheme VII
(Scheme Removed)
Compounds of Formula 29 can be prepared according to Scheme VII. Thus, compounds of Formula 26 can be deprotected with thiophenol or thioglycolic acid to give compounds of Formula 27. Compounds of Formula 27 can be reacted with phenyl chloroformate to form compounds of Formula 27a. Compounds of Formula 27 can be reacted with compounds of Formula R3NCO to form compounds of Formula 28. Compounds of Formula 27a can be reacted with amines of Formula R3NH2 to form compounds of Formula 28. Compounds of Formula 28 can finally be deprotected to form compounds of Formula 29.
Compounds of Formula 26 can be deprotected in the presence of one or more inorganic bases, for example, cesium carbonate, sodium carbonate, sodium hydrogen carbonate, potassium carbonate or calcium carbonate in one or more solvents, for example, nitriles (e.g. acetonitrile or propionitrile), acetates (e.g. ethyl acetate), polar aprotic solvents (e.g. dimethylsulfoxide or dimethylformamide), ketones (e.g. dimethylketone or ethylmethylketone), ethers (e.g. diethylether, dioxane or tetrahydrofuran) or in mixture thereof. Compounds of Formula 27 can be reacted in one or more solvents, for example, chlorinated solvents (e.g. dichloromethane, dichloroethane, chloroform or tetrachloromethane), nitriles (acetonitrile or propionitrile) or mixture thereof. Compounds of Formula 27 can be reacted with phenyl chloroformate in the presence of one or more bases, for example, triethylamine, trimethylamine or pyridine, in one or more chlorinated solvents, for example, dichloromethane, dichloroethane, chloroform or carbon tetrachloride. Compounds of Formula 27a can be reacted in the presence of one or more bases, for example, triethylamine, trimethylamine or pyridine, in one or more chlorinated solvents, for example, dichloromethane, dichloroethane, chloroform or carbon tetrachloride. Compounds of Formula 28 can be deprotected in the presence of one or more acids, for example, trifluoro
12 acetic, hydrochloric, hydrobromic or hydroiodic acid in one or more polar protic solvents, for example, methanol, ethanol, propanol, isopropanol, butanol or water.
In the above schemes, where the specific bases, oxidizing agents, reducing agents, coupling agents, solvents, etc., are mentioned, it is to be understood that other bases, oxidizing agents, reducing agents, coupling agents, solvents, etc., known to those skilled in the art may be used. Similarly, the reaction temperature and duration may be adjusted according to the desired needs.
The compounds disclosed herein possess antimicrobial activity against gram-positive, gram-negative, anaerobic bacteria and fungal infections. They are useful as antimicrobial agents for the treatment of infections diseases in human and animal.
Compounds of the present invention useful for such purpose are listed below:
4-chloro-N-({[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}carbonyl) benzenesulfonamide (Compound No. 1),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N'-(4-morpholin-4-ylphenyl)urea (Compound No. 2),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N'-[3-(2-furyl)-1H-pyrazol-5-yl]urea (Compound No. 3),
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]-N'-(5-oxo-1 -phenyl-4,5-dihydro-1H-pyrazol-3-yl)urea (Compound No. 4),
N-[2-({[(1S)-2-cycIohexyl-l-methylethyl]amino}methyl)phenyl]-N'-(4-methoxy-l,2-benzisoxazol-3-yl)urea (Compound No. 5),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N'-(3,4-dimethylisoxazol-5-yl)urea (Compound No. 6),
N-[2-( {[(1S)-2-cyclohexy 1-1 -methylethy l]amino} methyl)phenyl]-N-[ 1 -methyl-3-(2-thienyl)-1H-pyrazol-5-yl]urea (Compound No. 7),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-1H-imidazoIe-4-sulfonamide (Compound No. 8),
N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-1H-imidazole-4-sulfonamide (Compound No. 9),
N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino} sulfonyl)phenyl]acetamide (Compound No. 10),
4-amino-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]
benzenesulfonamide (Compound No. 11),
N-[4-( {[2-({ [(1S)-2-cyclopentyl-1 -methylethyl]amino} methyl)phenyl]amino} sulfonyl) phenyl]thiophene-2-sulfonamide (Compound No. 12),
2-thienylmethyl [2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]carbamate (Compound No. 13),
2-thienylmethyl [2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]carbamate (Compound No. 14),
N-[2-({[(lS)-2-cyclopentyl-l-methyIethyl]amino}methyl)phenyl]-5-(2,3,4-trimethoxyphenyl) thiophene-2-sulfonamide (Compound No. 15),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-{3-[(E)-(hydroxyimino) methyl]-1H-pyrrol-1-yl}benzenesulfonamide (Compound No. 16),
A'-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(3-formyl-1H-pyrrol-l-yl)benzamide (Compound No. 17),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyI]amino}methyl)phenyl]-N'-[4-(l,2,3-thiadiazol-4-yl)phenyl]urea (Compound No. 18),
N-[2-({[(16)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-l-benzofuran-6-carboxamide (Compound No. 19),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-3,5-dimethylisoxazole-4-sulfonamide (Compound No. 20),
N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl)phenyl] isoxazole-5-carboxamide (Compound No. 21),
N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl) phenyl]-3,5-dimethylisoxazole-4-sulfonamide (Compound No. 22),
N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl)phenyl] -1-methyl-1H-imidazole-4-sulfonamide (Compound No. 23),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(l-hydroxyethyl) Benzenesulfonamide (Compound No. 24),
pyridin-3-ylmethyl [2-({[(l.S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]carbamate (Compound No. 25),
pyridin-3-ylmethyl [2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]carbamate (Compound No. 26),
pyridin-3-ylmethyl [2-({[(1S',2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl) phenyl]carbamate (Compound No. 27),
N-[2-( {[(1S)-2-cyclopentyI-1 -methyIethyl]amino} methyl)phenyl]-1 -pyrazin-2-yl-1H-imidazole-4-sulfonamide (Compound No. 28),
methyl- l-benzothiophene-2-sulfonamide (Compound No. 29),
ethyl 3-[5-({[2-({[(liS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl)-2-thienyl]benzoate (Compound No. 30),
4-acety l-N-[4-( {[2-( {[(1 S)-2-cyclohexy 1-1 -methy lethy l]amino} methy l)phenyl]amino} sulfonyl)phenyl]benzenesulfonamide (Compound No. 31),
N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl)phenyl] -2,4-dimethyl-l,3-thiazole-5-sulfonamide (Compound No. 32),
N-l,3-benzothiazol-2-yl-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] Urea (Compound No. 33),
N-[2-({[(lS)-2-cyclohexyl-l -methy lethyl]amino}methyl)phenyl]-N'-[4-(l,3-oxazol-5-yl)phenyl]urea (Compound No. 34),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino} methy l)phenyl]-4-(l,3-dioxo-l,3-dihydro-2H-isoindol-2-yl)benzenesulfonamide (Compound No. 35),
N-[2-({[(1S,2S)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl)phenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide (Compound No. 36),
N-[2-( {[(1S,2S)-2-cyclohexyl-2-hydroxy-1 -methylethyl]amino}methyl)phenyl]-1 -benzothiophene-2-sulfonamide (Compound No. 37),
N-[2-({[(1S,2S)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-5-ylthiophene-2-sulfonamide (Compound No. 38),
N-[2-({[(1S,2S)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino} methy l)phenyl]-2-(trifluoroacetyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide (Compound No. 39),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(3-formyl-1H-pyrrol-1-yl)benzenesulfonamide (Compound No. 40),
N-[3-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)pyridin-2-yl]-5-isoxazol-5-ylthiophene-2-sulfonamide (Compound No. 41),
N-[3-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)pyridin-2-yl]-5-isoxazol-3-ylthiophene-2-sulfonamide (Compound No. 42),
N-[3-( {[(1S)-2-cyclohexy 1-1 -methy lethyl]amino}methyl)pyridin-2-yl]-4-(l H-pyrrol-1-yl)benzenesulfonamide (Compound No. 43),
N-[2-( {[(1S)-2-cyclopenty 1-1 -methylethyl]amino}methyl)phenyl]-4-(3-formyl-1H-pyrrol-1 -yl)benzenesulfonamide (Compound No. 44),
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyljamino} methy l)phenyl]-4-(2-oxo-1,3-oxazolidin-3-yl)benzenesulfonamide (Compound No. 45),
thiophene-3-sulfonamide (Compound No. 46),
N-[2-({ [(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]-5-( 1 -methyl-1H-pyrazol-4-yl)thiophene-2-sulfonamide (Compound No. 47),
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino}methyl)phenyl]-1 -(2-thienylsulfonyl)-1H-imidazole-4-sulfonamide (Compound No. 48),
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2,l,3-benzothiadiazole-4-sulfonamide (Compound No. 49),
N-[4-( {[2-( {[(1S)-2-cyclopenty 1-1 -methylethyl]amino} methyl)phenyl]amino} sulfony I) phenyl]-l-methyl-1H-imidazole-4-sulfonamide (Compound No.50),
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-[(methylsulfonyl)amino] Benzenesulfonamide (Compound No. 51),
4-[(butylsulfonyl)amino]-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] benzenesulfonamide (Compound No. 52),
N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-[(ethylsulfonyl)amino] Benzenesulfonamide (Compound No. 53),
5-chloro-N'-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino} sulfonyl)phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide (Compound No. 54),
methyl 4-({[4-({[2-({[(1S)-2-cyclohexyl-1 -methylethyl]amino}methyl)phenyl]amino} sulfonyl)phenyl]amino}sulfonyl)-2,5-dimethyl-3-furoate (Compound No. 55),
methyl 5-({[4-({[2-({[(1S)-2-cyclohexyl-1 -methylethyl]amino}methyl)phenyl]amino} sulfonyl)phenyl]amino}sulfonyl)-3-methylthiophene-2-carboxylate (Compound No. 56),
methyl 5-({[4-({[2-({[(1S)-2-cyclohexyl-1 -methylethy l]amino} methyl)phenyl]amino} sulfonyl)phenyl]amino}sulfonyl)-2-furoate (Compound No. 57),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-(3-oxo-l,3-dihydro-2-benzofuran-5-yl)urea (Compound No. 58),
2-[({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}carbonyl) aminojbenzamide (Compound No. 59),
N-[2-({[(1S)-2-cyclohexyl-l -methylethy l]amino}methyl)phenyl]-jV-isoquinolin-5-ylurea (Compound No. 60),
N-[2-({[(1S)-2-cyclohexyl-l -methylethy l]amino}methyl)phenyl]-jV'-morpholin-4-ylurea (Compound No. 61),
A'-l,3-benzothiazol-6-yl-N'-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] urea (Compound No. 62),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N'-l,3-thiazol-2-ylurea (Compound No. 63),
ethyl 3-[5-({[2-({[(1S)-2-cyclohexyI-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl)-2-thienyljbenzoate (Compound No. 64),
A'-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-l,3-benzothiazole-2-sulfonamide (Compound No. 65),
N-[2-{ {[(1S,2R)-2-cyclohexyl-2-hydroxy-1 -methylethyl]amino} methyl)pheny l]-4-(1H-1,2,4-triazol-l-yl)benzenesulfonamide (Compound No. 66),
yl)benzenesulfonamide (Compound No. 67),
N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl)phenyl] -2-(trifluoroacetyl)-l,2,3,4-tetrahydroisoquinoline-7-sulfonamide (Compound No. 68),
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]-4-pyridin-3-ylbenzenesulfonamide (Compound No. 69),
N-[2-( {[(1S)-2-cyclopentyl-1 -methylethyl]amino}methyl)phenyl]-4-pyridin-3-ylbenzenesulfonamide (Compound No. 70),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-pyrimidin-5-ylbenzenesulfonamide (Compound No. 71),
N-[2-({[(1S)-2-cyclopentyl-l -methylethyl]amino} methyl)phenyl]-4-pyrimidin-5-ylbenzenesulfonamide (Compound No. 72),
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]-4-( 1 -methyl-1H-pyrazol-4-yl)benzenesulfonamide (Compound No. 73),
N-[2-( {[(1S)-2-cyclopentyl-1 -methylethy l]amino} methyl)phenyl]-4-( 1 -methyl-1H-pyrazol-4-yl)benzenesulfonamide (Compound No. 74),
N-[2-( {[(1S,2R)-2-cyclohexyl-2-hydroxy-1 -methylethyl]amino} methyl)phenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide (Compound No. 75),
N-[2-({[(lS',2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-5-ylthiophene-2-sulfonamide (Compound No. 76),
N-[2-( {[(1S',2R)-2-cyclohexyl-2-hydroxy-1 -methylethyl]amino}methyl)phenyl]-1 -benzothiophene-2-sulfonamide (Compound No. 77),
N-[2-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl)phenyl] -1 -methyl-1H-imidazole-4-sulfonamide (Compound No. 78),
N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino} methyl)phenyI]amino}sulfonyl)phenyl] -1 -methyl-1H-imidazole-4-sulfonamide (Compound No. 79),
5-chloro-N-[4-( {[2-({ [(1S)-2-cyclopentyl-1 -methylethyl]amino} methyl)phenyl]amino} sulfonyl)phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide (Compound No. 80),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N,N-dimethylsulfamide (Compound No. 81),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(l,2,3-thiadiazol-4-yl)benzenesulfonamide (Compound No. 82),
N-[2-( {[(1S)-2-cyclohexyl-l -methylethyl]amino} methyl)phenyl]-4-( 1,3-oxazol-5-yl)benzenesulfonamide (Compound No. 83),
N-[3-({[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl) phenyl]thiophene-2-sulfonamide (Compound No. 84),
N-[2-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl) phenyl]thiophene-2-sulfonamide (Compound No. 85), 3-amino-N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] benzenesulfonamide (Compound No. 86),
2-am ino-N-[2-( {[(1S)-2-cyclohexy 1-1 -methy lethy l]am ino} methyl)phenyl] benzenesulfonamide (Compound No. 87),
N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl) phenyl]-2,4-dimethyl-l,3-thiazole-5-sulfonamide (Compound No. 88),
N-[3-( {[2-({ [(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]amino} sulfonyl) phenyl]-3,5-dimethylisoxazole-4-sulfonamide (Compound No. 89),
N-[3-({[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino} methy l)phenyl]amino} sulfonyl) phenyl]isoxazole-5-carboxamide (Compound No. 90),
N-[3-( {[2-({ [(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]amino} sulfonyl) phenyl]thiophene-3-sulfonamide (Compound No. 91),
ethyl 5-{[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl) phenyl]amino}-5-oxopentanoate (Compound No. 92),
2-amino-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-l,3-benzothiazole-5-sulfonamide (Compound No. 93),
5-chloro-N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino} sulfonyI)phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide (Compound No. 94),
N-[2-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino} sulfonyl) phenyl]-2,4-dimethyl-l,3-thiazole-5-sulfonamide (Compound No. 95),
N-[4-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]amino} sulfonyl) phenyl]thiophene-3-sulfonamide (Compound No. 96),
N-(2- {[[(1S)-2-cyclohexyI-1 -methylethyl](methylsulfonyl)amino]methyl} phenyl)-2-[(methylsulfonyl)amino]benzenesulfonamide (Compound No. 97),
N-[2-( {[(1S)-2-cyclopenty 1-1 -methylethyl]amino}methyl)phenyl]-4-(1H-pyrazol-1 -yl)benzenesulfonamide (Compound No. 98),
N-[2-({[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]-4-(1H-pyrazol-1 -yl)benzenesulfonamide (Compound No. 99),
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]-3-fluoro-4-( 1H-1,2,4-triazol-1 -yl)benzenesulfonamide (Compound No. 100),
[5-(2-thienyl)isoxazol-3-yl]methyl [2-({[(lS)-2-cyclohexyl-l-methylethyl]amino} methyl) phenyl]carbamate (Compound No. 101),
N-[(1S)-2-cyclopentyl-l-methylethyl]-2-[(2-thienylsulfonyl)amino]benzamide (Compound No.
102),
N-[(1S)-2-cyclohexyl-l-methylethyl]-2-[(2-thienylsulfonyl)amino]benzamide (Compound No.
103),
methyl [5-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}sulfonyl)-1H-benzimidazol-2-yl]carbamate (Compound No. 104),
methyl [6-({[4-({[2-({[(1S)-2-cyclohexyl-1 -methylethyl]amino}methyl)phenyl]amino} sulfonyl)phenyl]amino}sulfonyl)-1H-benzimidazol-2-yl]carbamate (Compound No. 105),
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]-4-[(1E)-N-hydroxyeth animidoyljbenzenesulfonamide (Compound No. 106),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino} methy l)phenyl]-4-[(lE)-N-methoxyethan imidoyl]benzenesulfonamide (Compound No. 107),
4-{[amino(imino)methyl]amino}-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino} methyl) phenyl]benzenesulfonamide (Compound No. 108),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]sulfamide (Compound No. 109),
N-[4-({[2-({[(1S)-2-cyclohexyl-l-methy lethyl]amino}methyl)phenyl]amino}sulfonyl) phenyl]-4-[(lE)-N-hydroxyethanimidoyl]benzenesulfonamide (Compound No. 110),
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-3-{[(isopropylamino) carbonyl]amino}benzenesulfonamide (Compound No. III),
ethyl (2Z)-4-{[2-({[(1S)-2-cyclohexyl-1 -methylethyl]amino} methy l)phenyl]amino} -4-oxobut-2-enoate (Compound No. 112),
pharmaceutically acceptable salts, pharmaceutical^ acceptable solvates, stereoisomers, prodrugs, metabolites and N-oxide thereof.
Because of their antimicrobial activity, the compounds described herein may be administered to an animal for treatment orally, topically, rectally, internasally, or by a parenteral route. The pharmaceutical compositions of the present invention comprise a pharmaceutical^ effective amount of compounds described herein formulated together with one or more pharmaceutically acceptable carriers.
Solid form preparations for oral administration include capsules, tablets, pills, powders, granules, cachets and suppositories. For solid form preparations, the active compound can be mixed with at least one inert, pharmaceutical ly acceptable excipients or carrier, for example, sodium citrate, dicalcium phosphate and/or a filler or extenders, for example, starches, lactose, sucrose, glucose, mannitol and silicic acid; binders, for example, carboxymethylcellulose, alginates, gelatins, polyvinylpyrrolidinone, sucrose, or acacia; disintegrating agents, for example, agar-agar, calcium carbonate, potato starch, alginic acid, certain silicates and sodium carbonate; absorption acceletors, for example, quaternary ammonium compounds; wetting agents, for example, cetyl alcohol, or glycerol mono stearate; adsorbants, for example, Kaolin; lubricants , for example, talc, calcium stearate, magnesium stearate, solid polyethyleneglycol, sodium luaryl sulphate and mixture thereof. In the case of capsules, tablets, or pills, the dosage form may also comprise buffering agents.
The solid preparation of tablets, capsules, pills and granules can be prepared with coating and shells, for example, enteric coating and other coatings well known in the pharmaceutical formulating art.
Liquid form preparations for oral administration can include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. For liquid form preparations, the active compound can be mixed with water or other solvent, solubilizing agents and emulsifiers, for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-butylene glycol, dimethylformamide, oils, for example, cottonseed, groundnut, corn, germ, olive, castor and sesame oil), glycerol, and fatty acid esters of sorbitan and mixture thereof. Besides inert diluents, the oral composition can also include adjuvants, for example, wetting agents, emulsifying agents, suspending agents, sweetening agents, flavouring agents and perfuming agents.
Injectible preparations, for example, sterile injections, aqueous suspensions may be formulated according to the art using suitable dispersing or wetting and suspending agent. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride.
Dosage forms for tropical or transdermal administration of compounds provided herein include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active compound can be admixed under sterile condition with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulations, eardrops, eye ointments, powder and solution are also contemplated as being within the scope of this invention.
The pharmaceutical preparation can be provided in a unit dosage form. In such forms, the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be packaged preparation, the package containing discrete capsules, powders, in vials or ampoules, and ointments capsule, sachet, tablet, gel, cream itself or it can be the appropriate number of any of these packaged forms.
Examples set forth below demonstrate general synthetic procedures for the preparation of representative compounds. The examples are provided to illustrate particular aspect of the disclosure and do not constrain the scope of the present invention as defined by the claims.
EXAMPLES
General Procedures
Example 1: Preparation of compounds of Formula 4
To a solution of a compound of Formula 2 (1.0 equiv.) in pyridine, a compound of Formula 3 (1.2 equiv.) was added portion wise at about 0-5 C. The reaction mixture was allowed to come at an ambient temperature and stirred overnight. The solvent was evaporated under reduced pressure. Water was added to the residue, which was then extracted with ethyl acetate. The organic layer was washed with water, brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography to yield the desired product.
Example 2: Preparation of compounds of Formula 5
To a solution of compound of Formula 4 (1.0 equiv.) in dichloromethane (20-30 mL), cooled to °C, was added Dess Martin Periodinane (1.5 equiv.). The reaction mixture was stirred overnight at an ambient temperature, filtered, and the mother liquor was washed with aqueous sodium bicarbonate solution. The organic layer was dried and evaporated under reduced pressure. The residue was purified by column chromatography to give the desired product.
Example 5: Preparation of compounds of Formula 7
A compound of Formula 6 (1.0 equiv.) and a compound of Formula R3COOH (1.2 equiv.) were taken in dry dimethylformamide (3-10 mL) and cooled to 0 °C. 1 -hydroxybenzotriazole (1.2 equiv.) and N-Methylpyrrolidone (3.0 equiv.) were added and stirred for about 15 minutes. l-Ethyl-3-[3-(dimethylamino)propyl]carbodimide (1.5 equiv.) was added and the resulting mixture was stirred at an ambient temperature for about 12 hours. The reaction mixture was then quenched with water and extracted in dichloromethane. The organic layer was washed with water, brine and dried over anhydrous sodium sulphate. Solvent was removed under reduced pressure and the residue was purified over silica gel column to yield the desired compounds.
Example 6: Preparation of compounds of Formula 8
Compound of Formula 7 (1.0 equiv.) was taken in dry tetrahydrofuran (10-15 mL) and tetrabutylammonium fluoride (1.2 equiv.) was added. After stirring for about 1 hour at an ambient temperature, solvent was removed under reduced pressure and the residue was extracted in ethyl acetate. Organic layer was washed with water, brine and dried over anhydrous sodium sulphate. Solvent was removed and the residue was purified over silica gel column to yield the desired compounds.
Example 7: Preparation of compounds of Formula 9
Compound of Formula 9 was prepared using the procedure described for compound of Formula 5.
Example 8: Preparation of compounds of Formula 11
Compound 6 (1.0 equiv.) was taken in dry dichloromethane (5-10 mL) and imidazole (1.5 equiv.) and N,N'-carbonyldiimidazole (1.5 equiv.) were added. Resulting mixture was stirred at room temperature for about 2 hours, quenched with water and extracted in dichloromethane. The organic layer was washed with water, brine and dried over anhydrous sodium sulphate. The solvent was removed and the residue was dissolved in dichloromethane (5-10 mL) and imidazole (1.5 equiv.) and a compound of Formula R2CH2OH (1.2 equiv.) were added. The resulting mixture was stirred at an ambient temperature for about 5 hours, quenched with water and extracted in dichloromethane. The organic layer was washed with water, brine and dried over anhydrous sodium sulphate. Solvent was removed under pressure and the residue was purified over silica gel column to obtain the desired compound.
Example 9: Preparation of compounds of Formula 12
Compound of Formula 11 (1.0 equiv.) was taken in dry tetrahydrofuran (10-15 mL) and Tetrabutylammonium Fluoride (1.2 equiv.) was added. After stirring for about 1 hour at an ambient temperature, solvent was removed under reduced pressure and the residue was extracted in ethyl acetate. The organic layer was washed with water, brine and dried over anhydrous sodium sulphate. Solvent was removed and the residue was purified over silica gel column to yield the desired compound.
Example 10: Preparation of compounds of Formula 13
Compound of Formula 13 was prepared using the procedure described for compound of Formula 5.
Example 11: Preparation of (2-hvdroxy-l-methylethyl)-carbamic acid tert-butyl ester of Formula 16
To a solution of L-alaniol (1.0 equiv.) in dichloromethane (10-15 mL) was added di-tert-
Butyl dicarbonate (1.1 equiv.) slowly at about 0-5 °C. The reaction mixture was stirred for
about 3 hours at an ambient temperature. The reaction mixture was diluted with
dichloromethane and washed with water, brine, dried over anhydrous sodium sulfate, and
evaporated in vacuo. The residue was purified by column chromatography to form (2-hydroxy-
l-methylethyl)-carbamic acid tert-butyl ester.
Example 12: Preparation of 2-methyl-aziridine-l-carboxvlic acid tert-butyl ester of Formula 17 To a solution of (2-hydroxy-l-methylethyl)-carbamic acid tert-butyl ester of Formula 16 (1.0 equiv.) in ether (20-30 mL) was added tosyl chloride (1.3 equiv.). The reaction mixture was stirred for about 15 hours and cooled to 0 °C. Potassium hydroxide (about 1.25 equiv., powdered) was added and stirring was continued for about 15 minutes. Additional 1.25 equiv. of potassium hydroxide was added and again the reaction mixture was stirred for additional 15 minutes. The reaction mixture was refluxed at about 40-50 °C for about 3 hours. The reaction mixture was diluted with water and the compound was extracted with ethyl acetate. The organic layer was dried and evaporated under reduced pressure. The product was purified by column chromatography over silica gel to form 2-methyl-aziridine-l-carboxylic acid tert-butyl ester.
Example 13: Preparation of compounds of Formula 18
In a two-necked round bottom flask Mg (5.03 equiv.) was suspended in tetrahydrofuran (dry, 100-125 mL), cooled to 0 °C, added slowly a compound of Formula Cy-Ha (5.03 equiv.), and diluted with tetrahydrofuran (100-110 mL). A crystal of iodine was added to titrate the reaction. The reaction mixture was stirred for about 2 hours. The reaction mixture was cooled to about -40 °C and added CuBr-Me2S complex (0.1 equiv.) to it. 2-methyl-aziridine-l-
carboxylic acid tert-butyl ester of Formula 17 (1.0 equiv.) dissolved in tetrahydrofuran was added slowly to the reaction mixture. The reaction mixture was stirred for about 2 hours and quenched by adding saturated ammonium chloride solution. The reaction mixture was stirred overnight and was extracted with ethyl acetate. The organic layer was dried, evaporated under reduced pressure and purified by column chromatography to form the desired compound of Formula 18.
Example 14: Preparation of compounds of Formula 19
The deprotection of compounds of Formula 18 to give compounds of Formula 19 was carried out following the methods well known in the art.
Example 20: Preparation of compounds of Formula 20
To a solution of compound of Formula 5 (1.0 equiv.) in methanol (20-30 mL) was added compound of Formula 19 (2.45 equiv.). After stirring for about 1 hour, sodium cyanoborohydride (2.45 equiv.) was added to the reaction mixture. The reaction mixture was stirred overnight and then the solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane, washed with water, brine and dried over anhydrous sodium sulfate. The product was purified by column chromatography to form the desired compound of Formula 20.
Example 21: Preparation of compounds of Formula 21 and 22
To a solution of compound of Formula 9 (1.0 equiv.) or 13 (1.0 equiv.) in methanol (20-30 mL) was added compound of Formula 19 (2.45 equiv.). After stirring for about 1 hour, sodium cyanoborohydride (2.45 equiv.) was added to the reaction mixture. The reaction mixture was stirred overnight and then evaporated the solvent under reduced pressure. The residue was dissolved in dichloromethane, washed with water, brine and dried over anhydrous sodium sulfate. The product was purified by column chromatography to form the desired compound.
Example 25: Preparation of compounds of Formula 25
Compound of Formula 23 (1.0 equiv.) was taken in pyridine (5-10 mL) and cooled to 0 °C. To this mixture, compound of Formula R3SO2CI (1.2 equiv.) was added in portion wise and the contents were stirred for about 1 hour at 0 °C. The reaction mixture was quenched with water and extracted in dichloromethane. The organic layer was washed with dilute hydrochloric acid solution, water and brine and evaporated to get the crude product of Formula 24.
Compound of Formula 24 (1.54 equiv.) was taken in a round bottomed flask and cooled to 0 °C. To this ethanolic hydrochloride (5-10 mL) was added and the reaction mixture was stirred overnight at an ambient temperature. Evaporation of the solvent gave the salt of the amine, which was taken in dichloromethane, cooled and basified using triethylamine to get the free amine. The crude product was purified on preparative thin layer chromatography to yield the desired compound of Formula 25.
Example 26: Preparation of compounds of Formula 27
Compound of Formula 26 (1.0 equiv.) was taken in acetonitrile (10-20 mL) and to it cesium carbonate (4.0 equiv.) and thiophenol (3.0 equiv.) was added at an ambient temperature. The reaction mixture was heated at about 50 °C for about 4 hours, cooled to an ambient temperature, quenched with water and extracted with ethyl acetate. Evaporation of solvent gave the crude product, which was purified over silica gel column chromatography to yield the desired compound of Formula 27.
Example 27: Preparation of compounds of Formula 27a
Compound of Formula 27 (1.0 equiv.) was taken in dichloromethane (15-20 mL) and cooled to °C. To this triethylamine (1.5 equiv.) was added followed by dropwise addition of phenyl chloroformate (1.2 equiv.) and the reaction mixture was stirred at °C for about half an hour. The reaction mixture was then quenched with water and extracted with dichloromethane. The solvent was evaporated and to form compound of Formula 27a.
Example 28: Preparation of compound of Formula 29
Step 1:
Method A: The amine of Formula 27 (1.0 equiv.) was taken in dichloromethane (5-10 mL) and cooled to 0 °C. To this mixture, R^ NCO (1.2 equiv.) was added and the reaction mixture was stirred at an ambient temperature overnight. It was then filtered and the filtrate was evaporated to get compound of Formula 28.
Method B: Compound of Formula 27a (1.07 equiv.) was taken in dichloroethane (5-10 mL) and to it compound of Formula R3NH2 (1.1 equiv.) was added followed by the addition of triethylamine (1.5 equiv.). The reaction mixture was then heated at about 90 °C for about 8 hours, cooled to an ambient temperature and extracted with dichloromethane, washed with sodium hydroxide solution (5%), water and dried with brine and sodium sulfate. The solvent was evaporated and the product thus obtained was purified by column chromatography to yield compound of Formula 28.
Step 2:
Compound of Formula 28 (1.0 equiv.) was taken in an round bottom and cooled to 0 °C. To this mixture, ethanolic hydrochloride (10-15 mL) was added and the reaction mixture was stirred overnight at room temperature for about 5 hours. Evaporation of the solvent gave the salt of the amine, which was taken in dichloromethane, cooled and basified using triethylamine to get the free amine. The crude product was then purified by preparative thin layer chromatography.
The following compounds were prepared analogously, following the above general procedures:
Compound No. 1: 4-chloro-N-({[2-({[(1S)-2-cyclohexyl-lmethylethyl]amino}methyl)phenyl] amino}carbonyl)benzenesulfonamide, Mass (m/z): 464.1; m. pt.: 162-163;
Compound No. 2:N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N'-(4-morpholin-4-ylphenyl)urea, Mass (m/z): 451.3; m. pt.: 68-70;
Compound No. 3: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N'-[3-(2-furyl)-1H-pyrazol-5-yl]urea, Mass (m/z): 422.2; m. pt.: 103-105;
Compound No. 4:N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-(5-oxo-l-phenyl-4,5-dihydro-1H-pyrazol-3-yl)urea, Mass (m/z): 448.2; m. pt.: 162-164;
Compound No. 5: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N'-(4-methoxy-l,2-benzisoxazol-3-yl)urea, Mass (m/z): 437.2; m. pt.: 70-71;
Compound No. 6: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N'-(3,4-dimethylisoxazol-5-yl)urea, Mass (m/z): 385.2; m. pt.: 53-55;
Compound No. 7:N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-[l-methyl-3-(2-thienyl)-1H-pyrazol-5-yl]urea, Mass (m/z): 452.2; m. pt.: 105-107;
Compound No. 8: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-1H-imidazole-4-sulfonamide, Mass (m/z): 376.50; m. pt.: 55-56;
Compound No. 9: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-1H-imidazole-4-sulfonamide, Mass (m/z): 363.1; m. pt: 120-122;
Compound No. 10: N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]acetamide, Mass (m/z): 444.3; m. pt: 69-72;
Compound No. 11: 4-amino-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]benzenesulfonamide, Mass (m/z): 402.3; m. pt.: 74-76;
Compound No. 12: A^ 4-({[2-({[(13)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 534.1; m. pt: 93.8-95;
Compound No. 13: 2-thienylmethyl [2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]carbamate, Mass (m/z): 387.2;
Compound No. 14: 2-thienylmethyl [2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl]carbamate, Mass (m/z): 373.2;
Compound No. 15: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(2,3,4-trimethoxyphenyl)thiophene-2-sulfonamide, Mass (m/z): 545.1;
Compound No. 16: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-{3-[(E)-(hydroxyimino)methyl]-1H-pyrrol-l-yl}benzenesulfonamide, Mass (m/z): 495.1; m. pt.: 150-
152;
Compound No. 17: N-[2-({[(1S)-2-cyclohexyI-l-methylethyl]amino}methyl)phenyl]-4-(3-formyl-1H-pyrroI-l-yl)benzamide, Mass (m/z): 444.2; m. pt.: 84-86;
Compound No. 18: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-[4-(l,2,3-thiadiazol-4-yl)phenyl]urea, Mass (m/z): 450.2; m. pt.: 158-159;
Compound No. 19: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-l-benzofuran-6-carboxamide, Mass (m/z): 391.2;
Compound No. 20: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-3,5-dimethylisoxazole-4-sulfonamide, Mass (m/z): 406.2; m. pt: 104-106;
Compound No. 21: N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]isoxazole-5-carboxamide, Mass (m/z): 497.1;
Compound No. 22: N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]-3,5-dimethylisoxazole-4-sulfonamide, Mass (m/z): 561.0; m. pt.: 82-84;
Compound No. 23: N-[4-({[2-({[(l^ -2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]-l-methyl-1H-imidazole-4-sulfonamide, Mass (m/z): 546.1; m. pt.: 175-177;
Compound No. 24: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(l-hydroxyethyl)benzenesulfonamide, Mass (m/z): 431.1; m. pt.: 42-44;
Compound No. 25: pyridin-3-ylmethyl [2-({[(lS)-2-cyclohexyl-lmethylethyl]amino}methyl) phenyl]carbamate, Mass (m/z): 382.3;
Compound No. 26: pyridin-3-ylmethyl [2-({[(1S)-2-cyclopentyl-l-methylethyl]amino} methyl)phenyl]carbamate, Mass (m/z): 368.2;
Compound No. 27: pyridin-3-ylmethyl [2-({[(lS,,2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl)phenyl]carbamate, Mass (m/z): 398.1;
Compound No. 28: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-l-pyrazin-2-yl-1H-imidazole-4-sulfonamide, Mass (m/z): 441.2; m. pt.: 85-87;
Compound No. 29: 5-chloro-N-[2-({[(lS',2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}
methyl)phenyl]-3-methyl-l-benzothiophene-2-sulfonamide, Mass (m/z): 507.1; m. pt.: 110-112;
Compound No. 30: ethyl 3-[5-({[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-2-thienyl]benzoate, Mass (m/z): 527.1;
Compound No. 31: 4-acetyl-N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino} methyl)phenyl]amino}sulfonyl)phenyl]benzenesulfonamide, Mass (m/z): 584.2; m. pt.: 117-119;
Compound No. 32: N-[4-({[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]-2,4-dimethyl-l,3-thiazole-5-sulfonamide, Mass (m/z): 577.1; m. pt.: 72-
73;
Compound No. 33: N-l,3-benzothiazol-2-yl-N'-[2-({[(1S)-2-cyclohexyl-lmethylethyl]amino} methyl)phenyl]urea, Mass (m/z): 423.1; m. pt.: 74-75;
Compound No. 34: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-[4-(l,3-oxazol-5-yl)phenyl]urea, Mass (m/z): 433.2; m. pt: 133-135;
Compound No. 35: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(l,3-dioxo-l,3-dihydro-2H-isoindol-2-yl)benzenesulfonamide, Mass (m/z): 532.1; m. pt.: 142-144;
Compound No. 36: N-[2-({[(1S,2S)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl) phenyl]-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide, Mass (m/z): 458.2; m. pt.: 127.2-129.1;
Compound No. 37: N-[2-({[(lS,2S)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl) phenyl]-l-benzothiophene-2-sulfonamide, Mass (m/z): 459.0; m. pt.: 78.8-82.1;
Compound No. 38: N-[2-({[(1S',2S)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl) phenyl]-5-isoxazol-5-ylthiophene-2-sulfonamide, Mass (m/z): 476.0; m. pt: 89.3-93.8;
Compound No. 39: N-[2-({[(1S,2S)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl) phenyl]-2-(trifluoroacetyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide, Mass (m/z): 554.1; m. pt: 73.6-75.8;
Compound No. 40: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(3-formyl-1H-pyrrol-l-yl)benzenesulfonamide, Mass (m/z): 480.1; m. pt: 53-54;
Compound No. 41: N-[3-({[(l-S)-2-cyclohexyl-l-methylethyl]amino}methyl)pyridin-2-yl]-5-isoxazol-5-ylthiophene-2-sulfonamide, Mass (m/z): 461.0; m. pt: 107-108;
Compound No. 42: N-[3-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)pyridin-2-yl]-5-isoxazol-3-ylthiophene-2-sulfonamide, Mass (m/z): 447.0; m. pt.: 97-99;
Compound No. 43: N-[3-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)pyridin-2-yl]-4-(lH-pyrrol-l-yl)benzenesulfonamide, Mass (m/z): 453.2; m. pt.: 179-180;
Compound No. 44: N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}rnethyl)phenyl]-4-(3-formyl-1H-pyrrol-l-yl)benzenesulfonamide, Mass (m/z): 466.0; m. pt: 76-78;
Compound No. 45:N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(2-oxo-l,3-oxazolidin-3-yl)benzenesulfonamide, Mass (m/z): 472.2; m. pt: 75-77;
Compound No. 46:N-[4-({[2-({[(1S)-2-cycIohexyl-l-methylethyI]amino}methyl)phenyl] amino}sulfonyl)phenyl]thiophene-3-sulfonamide, Mass (m/z): 548.2; m. pt.: 162-165;
Compound No. 47: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(l-methyl-1H-pyrazol-4-l)thiophene-2-sulfonamide, Mass (m/z): 473.1; m. pt.: 85-87;
Compound No. 48: N-2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-l-(2-thienylsulfonyl)-1H-imidazole-4-sulfonamide, Mass (m/z): 523.0; m. pt.: 67-69;
Compound No. 49: N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2,l,3-benzothiadiazole-4-sulfonamide, Mass (m/z): 431.0; m. pt.: 72-74;
Compound No. 50: N-[4-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]-l-methyl-1H-imidazole-4-sulfonamide, Mass (m/z): 532.1; m. pt.: 114.6-116.2;
Compound No. 51: N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-[(methylsulfonyl)amino]benzenesulfonarnide, Mass (m/z): 466.1; m. pt.: 78.6-80.9;
Compound No. 52: 4-[(butylsulfonyl)amino]-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl] amino}methyI)phenyl]benzenesulfonamide, Mass (m/z): 522.2; m. pt.: 53-56;
Compound No. 53: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-[(ethylsulfonyl)amino]benzenesulfonamide, Mass (m/z): 494.1; m. pt.: 65-67;
Compound No. 54: 5-chloro-N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide, Mass (m/z): 594.2; m. pt: 75-78;
Compound No. 55: methyl 4-({[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]amino}sulfonyl)-2,5-dimethyl-3-furoate, Mass (m/z): 618.2; m. pt: 65-67;
Compound No. 56: methyl 5-({[4-({[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]amino}sulfonyl)-3-methylthiophene-2-carboxylate, Mass (m/z): 620.2; m. pt: 93-95;
phenyl]amino}sulfonyl)phenyl]amino}sulfonyl)-2-furoate, Mass (m/z): 590.2; m. pt: 109-111;
Compound No. 58: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N'-(3-oxo-l,3-dihydro-2-benzofuran-5-yl)urea, Mass (m/z): 422.2; m. pt.: 169-172;
Compound No. 59: 2-[({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}carbonyl)amino]benzamide, Mass (m/z): 392.2 (M-16); m. pt: 51-54;
Compound No. 60: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N'-isoquinolin-5-ylurea, Mass (m/z): 417.2; m. pt: 156-158;
Compound No. 61: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N'-morpholin-4-ylurea, Mass (m/z): 375.2; m. pt.: 132-134;
Compound No. 62: N-l,3-benzothiazol-6-yl-N'-[2-({[(1S)-2-cyclohexyl-l-methylethyl] amino}methyl)phenyl]urea, Mass (m/z): 423.1; m. pt.: 150-153;
Compound No. 63: A^ 2-({[(1S)-2-cyclohexyl-l-methyIethyl]amino}methyl)phenyl]-N'-1,3-thiazol-2-ylurea, Mass (m/z): 373.2; m. pt.: 51-54;
Compound No. 64: ethyl 3-[5-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-2-thienyl]benzoate, Mass (m/z): 541.1;
Compound No. 65: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-l,3-benzothiazole-2-sulfonamide, Mass (m/z): 444.1; m. pt: 80-82;
Compound No. 66: N-[2-({[(lS,2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl) phenyl]-4-(lH-l,2,4-triazol-l-yl)benzenesulfonamide, Mass (m/z): 470.1; m. pt.: 92-94;
Compound No. 67: N-[2-({[(1S',2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl) phenyl]-4-(lH-pyrrol-l-yl)benzenesulfonamide, Mass (m/z): 468.2; m. pt.: 88-90;
Compound No. 68: N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]-2-(trifluoroacetyl)-l,2,3,4-tetrahydroisoquinoline-7-sulfonamide, Mass (m/z): 693.2; m. pt: 114-116;
Compound No. 69: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-pyridin-3-ylbenzenesulfonamide, Mass (m/z): 464.2; m. pt: 60-62;
Compound No. 70: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-pyridin-3-ylbenzenesulfonamide, Mass (m/z): 450.2; m. pt: 135-137;
Compound No. 71: N-2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-pyrimidin-5-ylbenzenesulfonamide, Mass (m/z): 465.2; m. pt: 63-64;
Compound No. 72: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-pyrimidin-5-ylbenzenesulfonamide, Mass (m/z): 451.2; m. pt.: 120-122;
Compound No. 73:7N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(l-methyl-1H-pyrazol-4-yl)benzenesulfonamide, Mass (m/z): 467.2; m. pt: 75-77;
Compound No. 74: N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-(l-methyl-1H-pyrazol-4-yl)benzenesulfonamide, Mass (m/z): 453.2; m. pt: 65-67;
Compound No. 75: N-[2-({[(1S',2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino} methyl)phenyl]-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide, Mass (m/z): 458.2; m. pt: 142.5-145;
Compound No. 76: N-[2-({[(lS,2i?)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino} methyl)phenyI]-5-isoxazol-5-ylthiophene-2-sulfonamide, Mass (m/z): 476.2; m. pt.: 117.6-121.8;
Compound No. 77:N-[2-({[1S,2R)-2-cyclohexyl-2 -hydroxy-l-methylethyl]amino}methyl) phenyl]-l-benzothiophene-2-sulfonamide, Mass (m/z): 459.2; m. pt: 79.4-80.5;
Compound No. 78: N-[2-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino} sulfonyl)phenyl]-l-methyl-1H-imidazole-4-sulfonamide, Mass (m/z): 546.2; m. pt.: 115-118;
Compound No. 79: N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]-l-methyl-1H-imidazole-4-sulfonamide, Mass (m/z): 546.2; m. pt: 92-95;
Compound No. 80: 5-chloro-N-[4-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide, Mass (m/z): 580.1; m. pt.: 78.7-84.3;
Compound No. 81:N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N,N-dimethylsulfamide, Mass (m/z): 354.2;
Compound No. 82: N-[2-({[(1S)-2-cyclohexy 1-1 -methylethyl]amino}methyl)phenyl]-4-( 1,2,3-thiadiazol-4-yl)benzenesulfonamide, Mass (m/z): 471.2; m. pt.: 122-123;
Compound No. 83: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(l,3-oxazol-5-yl)benzenesulfonamide, Mass (m/z): 454.1; m. pt.: 50-52;
Compound No. 84: N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 548.1; m. pt.: 75-77;
Compound No. 85: N-[2-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]thiophene-2-sulfonamide, Mass (m/z): 548.1; m. pt: 75-77;
Compound No. 86: 3-amino-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] benzenesulfonamide, Mass (m/z): 402.2;
Compound No. 87: 2-amino-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] benzenesulfonamide, Mass (m/z): 402.1;
Compound No. 88: N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]-2,4-dimethyl-l,3-thiazole-5-sulfonamide, Mass (m/z): 577.1; m. pt: 77-78;
Compound No. 89:N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]-3,5-dimethylisoxazole-4-sulfonamide, Mass (m/z): 561.1; m. pt.: 63-66;
Compound No. 90: N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]isoxazole-5-carboxamide, Mass (m/z): 497.1; m. pt.: 97-99;
Compound No. 91: N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]thiophene-3-sulfonamide, Mass (m/z): 548.1; m. pt: 68-70;
Compound No. 92: ethyl 5-{[4-({[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]amino}-5-oxopentanoate, Mass (m/z): 544.2;
Compound No. 93: 2-amino-N'-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]-l,3-benzothiazole-5-sulfonamide, Mass (m/z): 459.1; m. pt.: 64-66;
Compound No. 94: 5-chloro-N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] phenyl]amino}sulfonyl)phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide, Mass (m/z): 594.1; m. pt.: 65-67;
Compound No. 95: N-[2-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyI]-2,4-dimethyl-l,3-thiazole-5-sulfonamide, Mass (m/z): 577.2; m. pt.: 71-74;
Compound No. 96: N-[4-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)
phenyl]amino}sulfonyl)phenyl]thiophene-3-sulfonamide, Mass (m/z): 534.1; m. pt.: 137.8-
141.2;
Compound No. 97: N-(2-{[[(1S)-2-cyclohexyl-l-methylethyl](methylsulfonyl)amino]methyl}
phenyl)-2-[(methylsulfonyl)amino]benzenesulfonamide, Mass (m/z): 558.1; m. pt.: 78-80 °C;
Compound No. 98:N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-(1H-pyrazol-l-yl)benzenesulfonamide, Mass (m/z): 439.1; m. pt.: 147-148;
Compound No. 99: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(1H-pyrazol-l-yl)benzenesulfonamide, Mass (m/z): 453.1;
Compound No. 100: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-3-fluoro-4-(lH-l,2,4-triazol-l-yl)benzenesulfonamide, Mass (m/z): 472.2; m. pt.: 136-137;
Compound No. 101: [5-(2-thienyl)isoxazol-3-yl]methyl [2-({[(l-S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]carbamate, Mass (m/z): 454.2;
Compound No. 102: N-[(1S)-2-cyclopentyl-l-methylethyl]-2-[(2-thienylsulfonyl)amino] benzamide, Mass (m/z): 393.1;
Compound No. 103: N-[(1S)-2-cycIohexyl-l-methylethyl]-2-[(2-thienylsulfonyl)amino] benzamide, Mass (m/z): 407.1;
Compound No. 104: methyl [5-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-1H-benzimidazol-2-yl]carbamate, Mass (m/z): 500.1; m. pt: 122-124;
Compound No. 105: methyl [6-({[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]amino}sulfonyl)-1H-benzimidazol-2-yl]carbamate, Mass (m/z): 655.2; m. pt.: 160-163;
Compound No. 106: N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-[(lE)-N-hydroxyethanimidoyl]benzenesulfonamide, Mass (m/z): 444.1; m. pt.: 144-147;
Compound No. 107: N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-[(lE)-N-methoxyethanimidoyl]benzenesulfonamide, Mass (m/z): 458.1;
Compound No. 108: 4-{[amino(imino)methyl]amino}-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]benzenesulfonamide, Mass (m/z): 445.1; m. pt.: 94-96;
Compound No. 109: N-[2-({[(1S)-2-cyclohexyl-l-tnethylethyl]amino}methyl)phenyl] sulfamide, Mass (m/z): 326.2;
Compound No. 110: N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)pheny!] amino}sulfonyl)phenyl]-4-[(lE)-N-hydroxyethanimidoyl]benzenesulfonamide, Mass (m/z): 599.2; tn.pt.: 120-122;
Compound No. 111: N-[2-({[(l,S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-3-{[(isopropylamino)carbonyl]amino}benzenesulfonamide, Mass (m/z): 487.2;
Compound No. 112: ethyl (2Z)-4-{[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}-4-oxobut-2-enoate, Mass (m/z): 373.2; m. pt.: 65-68.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
Microbiological activity
Microbroth minimum inhibitory concentration (MIC) was performed using NCCLS method in Cation adjusted Mueller Hinton broth for facultative cultures (S.aureus, Enterococcus) and Cation adjusted Mueller Hinton broth +2.5% lysed horse blood for S.pneumoniae. MIC against H.influenzae strains was performed by NCCLS broth dilution method using HTM broth. Overnight grown cultures were adjusted to 0.5 Mcfarland using normal saline and diluted 100 times. 1 mg/ml concentration of stock solution of drug in DMSO/distilled water/solvent given in NCCLS manual were prepared. NCCLS double dilutions were done to get the required concentration range of the drugs in the 96 well microtiter plates using the respective media. 100 µ1 of culture broth was added in wells already containing 100 µl
of broth containing antibiotic to get approximately 3-7x105 CFU/ml. The plates were incubated at 37 C for about 18- 24 hours. The concentration of drug at which there was complete disappearance of growth was considered as MIC.
Compounds of this invention have shown good activity againsts microbial strains. Some of the compounds disclosed herein have shown very good activity against microbial strains, for example, Streptococcus pneumoniae, Haemophilius influenzae, Streptococcus pyogenes or Staphylococcus aureus.

WE CLAIM:
1. A compound having the structure of Formula I,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy can be cyclopentyl or cyclohexyl; X can be CH2C(CH3) or CH(OH)C(CH3); Z can be CH2; Y can be NH or NS02CH3; X, can be CH or N; R can be NRiR2 -[wherein R1 and R2 can be independently hydrogen, SO2R3, COR3, CONHR3, CONHSO2R3 or COOCH2R3 (wherein R3 can be N(CH3)2, NH2, CH=CHCOOC2H5, (CH2)3COOC2H5, phenyl, 1,2,3,4-tetrahydroisoquinolinyl, 2,2,2-trifluoacetyl-l-(3,4-dihydro-lH-isoquinolin-2-yl), morpholinyl or heteroaryl)].
2. A compound, which is:
4-chloro-N-({ [2-( {[(1S)-2-cyclohexyl-1 methylethyl]amino} methyl)phenyl] amino}carbonyl)benzenesulfonamide,
N-[2-({[(lS)-2-cyclohexyl-l-methylethyl] amino}methyl)phenyl]-N'-(4 -morpholin-4-ylphenyl)urea,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-[3-(2-furyl)-lH-pyrazol-5-yl]urea,
N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyI]-N'-(5-oxo-l-phenyl-4,5-dihydro-1H-pyrazol-3-yl)urea,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N'-(4-methoxy-1,2-benzisoxazol-3-yl)urea,
N-[2-({[(l,S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-[l-methyl-3-(2-thienyl)-1H-pyrazol-5-yl]urea,
N-[2-({[(liS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-1H-imidazole-4-sulfonamide,
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-1H-imidazole-4-sulfonamide,
N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino} sulfonyl)phenyl]acetamide,
4-amino-N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] benzenesulfonamide,
N-[4-({[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]thiophene-2-suIfonamide,
2-thienylmethyl [2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] carbamate,
2-thienylmethyl [2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl] carbamate,
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-5-(2,3,4-trimethoxyphenyl)thiophene-2-sulfonamide,
(hydroxyimino)methyl]-1H-pyrrol-l-yl}benzenesulfonamide,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(3-formyl-1H-pyrrol-1 -yl)benzamide,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-[4-(l,2,3-thiadiazol-4-yl)phenyl]urea,
N-[2-( {[(1S)-2-cyclohexyl-1 -methy lethyl]am ino} methy l)pheny 1]-1 -benzofuran-6-carboxamide,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-3,5-dimethylisoxazole-4-sulfonamide,
N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]isoxazole-5-carboxamide,
N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino}
sulfonyl)phenyl]-3,5-dimethylisoxazole-4-sulfonamide,
N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]-l-methyl-1H-imidazole-4-sulfonamide,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyI]-4-(l-hydroxyethyl)benzenesulfonamide,
pyridin-3-ylmethyl [2-({[(1S)-2-cyclohexyl-lmethylethyl]amino}methyI) phenyl]carbamate,
pyridin-3-ylmethyl [2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl]carbamate,
pyridin-3-ylmethyl [2-({[(1S',2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino} methyl)phenyl]carbamate,
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyI)phenyl]-l-pyrazin-2-yl-1H-imidazole-4-sulfonamide,
5-chloro-N-[2-({[(1S',2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino} methyl)phenyl]-3-methyl-l-benzothiophene-2-sulfonamide,
ethyl 3-[5-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-2-thienyl]benzoate,
4-acetyl-N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]benzenesulfonamide,
N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]-2,4-dimethyl-l,3-thiazole-5-sulfonamide,
N-l,3-benzothiazol-2-yl-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino} methyl)phenyl]urea,
N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-[4-(l,3-oxazol-5-yl)phenyl]urea,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(l,3-dioxo-l,3-dihydro-2H-isoindol-2-yl)benzenesulfonamide,
N-[2-({[(1S,2S)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino} methyl) phenyl]-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide,
N-[2-({[(1S,2S)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl)phenyl]-l-benzothiophene-2-sulfonamide,
N-[2-( {[(1S,2S)-2-cyclohexyl-2-hydroxy-1 -methylethyl]amino}methyl) phenyl]-5-isoxazol-5-ylthiophene-2-sulfonamide,
N-[2-({[(1S,2S)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl)phenyl]-2-(trifluoroacetyl)-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(3-formyl-1H-pyrrol-l-yl)benzenesulfonamide,
N-[3-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)pyridin-2-yl]-5-isoxazol-5-ylthiophene-2-sulfonamide,
N-[3-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)pyridin-2-yl]-5-isoxazol-3-ylthiophene-2-sulfonamide,
N-[3-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)pyridin-2-yl]-4-(1H-pyrrol-l-yl)benzenesulfonamide,
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-(3-formyl-1H-pyrrol-1 -yl)benzenesulfonamide,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(2-oxo-l,3-oxazolidin-3-yl)benzenesulfonamide,
N-[4-({[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]thiophene-3-sulfonamide,
N-[2-({[(l«S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-5-(l-methyl-1H-pyrazol-4-l)thiophene-2-sulfonamide,
N-[2-( {[(1S)-2-cyclohexyl-1 -methy lethyl]amino} methyl)phenyl]-1 -(2-thienylsulfonyl)-1H-imidazole-4-sulfonamide,
N-[2-({[(lS)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-2,l,3-benzothiadiazole-4-sulfonamide,
N-[4-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]-l-methyl-1H-imidazole-4-sulfonamide,
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-[(methylsulfonyl)amino]benzenesulfonamide,
4-[(butylsulfonyl)amino]-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino} methyl)phenyl]benzenesulfonamide,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-[(ethylsulfonyl)amino]benzenesulfonamide,
5-chloro-N'-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide,
methyl 4-({[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]amino}sulfonyl)-2,5-dimethyl-3-furoate,
methyl 5-({[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]amino}sulfonyl)-3-methylthiophene-2-carboxylate,
methyl 5-({[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]amino}sulfonyl)-2-furoate,
dihydro-2-benzofuran-5-yl)urea,
2-[({[2-({[(1S)-2-cyclohexyl-l-methyIethyl]amino}methyl)phenyl]amino} carbonyl)amino]benzamide,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-isoquinolin-5-ylurea,
N-[2-({[(iS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-morpholin-4-ylurea,
N-1,3-benzothiazol-6-y l-N-[2-( {[(1S)-2-cyclohexy 1-1 -methy lethyl] amino}methyl)phenyl]urea,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N-l,3-thiazol-2-ylurea,
ethyl 3-[5-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)-2-thienyl]benzoate,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-l,3-benzothiazole-2-sulfonamide,
N-[2-({[(15',2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl) phenyl]-4-( 1H-1,2,4-triazol-1 -yl)benzenesulfonamide,
N-[2-({[(15',2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl)phenyl]-4-(1H-pyrrol-1-yl)benzenesulfonamide,
amino}sulfonyl)phenyl]-2-(trifluoroacetyl)-l,2,3,4-tetrahydroisoquinoline-7-
sulfonamide,
2-[( 1S)-2-cyclohexyl-1 -methylethyl]isoindolin-1 -one,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-pyridin-3-ylbenzenesulfonamide,
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-pyridin-3-ylbenzenesulfonamide,
N-[2-({[(lS )-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-pyrimidin-5-ylbenzenesulfonamide,
N-[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl)phenyl]-4-pyrimidin-5-ylbenzenesulfonamide,
N-[2-( {[(1S)-2-cyclohexyl-1 -methylethyl]amino} methyl)phenyl]-4-( 1 -methyl-1H-pyrazol-4-yl)benzenesulfonamide,
N-[2-({[(1S)-2-cyclopentyI-l-methylethyl]amino}methyl)phenyl]-4-(l-methyl-1H-pyrazol-4-yl)benzenesulfonamide,
N-[2-({[(15',2i?)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl) phenyl]-l,2,3,4-tetrahydroisoquinoline-6-sulfonamide,
N-[2-({[(15',2R)-2-cyclohexyl-2-hydroxy-l-methylethyl]amino}methyl)phenyl]-5-isoxazol-5-ylthiophene-2-sulfonamide,
N-[2-( {[(15',2R)-2-cyclohexyl-2-hydroxy-1 -methylethyl]amino}methyl)phenyl]-1 -benzothiophene-2-sulfonamide,
N-[2-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino} sulfonyl)phenyl]-1 -methyl-1H-imidazole-4-sulfonamide,
amino}sulfonyl)phenyl]-l -methyl- lH-imidazole-4-sulfonamide,
5-chloro-N-[4-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-N,N-dimethylsulfamide,
thiadiazol-4-yl)benzenesulfonamide,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(l,3-oxazol-5-yl)benzenesulfonamide,
N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]thiophene-2-sulfonamide,
N-[2-({[2-({[(15')-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino} sulfonyl)phenyl]thiophene-2-sulfonamide,
3-amino-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] benzenesulfonamide,
2-amino-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] benzenesulfonamide,
N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]-2,4-dimethyl-l,3-thiazole-5-sulfonamide,
N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino }sulfonyl)phenyl]-3,5-dimethylisoxazole-4-sulfonamide,
N-[3-( {[2-( {[(1S)-2-cyclohexyl-1 -methylethy l]amino} methyl)pheny 1] arnino}sulfonyl)phenyl]isoxazole-5-carboxamide,
N-[3-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]thiophene-3-sulfonamide,
ethyl 5-{[4-({[2-({[(1S)-2-cyclohexyl-1 -methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]amino}-5-oxopentanoate,
2-amino-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]-1,3-benzothiazole-5-sulfonamide,
5-chloro-N-[3-({[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]-l,3-dimethyl-1H-pyrazole-4-sulfonamide,
N-[2-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] amino}sulfonyl)phenyl]-2,4-dimethyl-l,3-thiazole-5-sulfonamide,
N-[4-({[2-({[(1S)-2-cyclopentyl-l-methylethyl]amino}methyl) phenyl]amino}sulfonyl)phenyl]thiophene-3-sulfonamide,
N-[2-({[(1S)-2-cyclopentyl-1 -methylethyl]amino}methyl)phenyI]-4-(1H-pyrazol-1 -yl)benzenesulfonamide,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-(1H-pyrazol-1 -yI)benzenesulfonamide,
N-[2-({ [(1S)-2-cyclohexyl-1 -methylethyl]amino}methyl)phenyl]-3-fluoro-4-( 1H-1,2,4-triazol-1 -yl)benzenesulfonamide,
[5-(2-thienyl)isoxazol-3-yl]methyl [2-({[(lS)-2-cyclohexyl-l-methylethyl]arnino} methyl)phenyl]carbamate,
N-[(1S)-2-cyclopentyl-l-methylethyl]-2-[(2-thienylsulfonyl)amino]benzamide,
N-[(lS)-2-cyclohexyl-l-methylethyl]-2-[(2-thienylsulfonyl)amino]
benzamide,
methyl [5-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]amino} sulfonyl)-1H-benzimidazol-2-yl]carbamate,
methyl [6-({[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)
phenyl]amino}sulfonyl)phenyl]amino}sulfonyl)-1H-benzimidazol-2-
yl]carbamate,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-[(lE)-N -hydroxyethanimidoyl]benzenesulfonamide,
N-[2-({[(lS)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-4-[(lE)-N-methoxyethanimidoyl]benzenesulfonamide,
4-{[amino(imino)methyl]amino}-N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]benzenesulfonamide,
N-[2-({[(1S)-2-cycIohexyl-l-methylethyl]amino}methyl)phenyl] sulfamide,
N-[4-({[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl] aminolsulfonyl)phenyl]-4-[(1E)-N-hydroxyethanimidoyl]benzenesulfonamide,
N-[2-({[(1S)-2-cyclohexyl-l-methylethyl]amino}methyl)phenyl]-3-{[(isopropylamino)carbonyl]amino}benzenesulfonamide,
ethyl (2Z)-4-{[2-({[(1S)-2-cyclohexy 1-1 -methylethyl]amino}methyl)
phenyl]amino}-4-oxobut-2-enoate,
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs, metabolites and N-oxide thereof.
3. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or 2 together with pharmaceutically acceptable carriers, excipients, or diluents.
4. A method for treating or preventing a subject suffering from a condition caused by or contributed to by bacterial infection or fungal infection, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or 2 or a pharmaceutical composition of claim 3.
5. The method according to claim 4 wherein bacterium is selected from Staphylococci, Enterococci, Streptococci, Haemophilus, Moraxalla, Escherichia, Chlamydia, Rickettsiae, Mycoplasm, Legionella, Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae, and the fungal organism is selected from Aspergillus, Blastomyces, Candida, Coccidiodes, Cryptococcus, Epidermophyton, Hendersonula, Histoplasma, Microsporum, Paecilomyces, Paracoccidiodes, Pneumocystis, Trichophyton, or Trichosporium.
6. The method according to claim 4 wherein the condition is selected from community acquired pneumonia, upper and lower respiratory tract infections, skin and soft tissue infections, hospital acquired lung infections or bone and joint infections, mastitis, catheter infection, foreign body, prosthesis infections and peptic ulcer disease.
7. A method for preparing compounds of Formula 20,
(Formula Removed)

(Formula 1, wherein X=CH2CH(CH 3), Y=NH, Z=CH2)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy, X1 and R3 are the same as defined in claim 1, which method comprises:
reacting compounds of Formula 5 with compounds of Formula 19
(Formula Removed)
to form compounds of Formula 20.
8. A method for the preparation of compounds of Formula 21,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy, X1 and R3 are the same as defined in claim 1, which method comprises:
reacting compounds of Formula 9 with compounds of Formula 19
(Formula Removed)
Formula 9 to form compounds of Formula 21.
9. A method for preparing compounds of Formula 22,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy, X1 and R3 are the same as defined in claim 1, which method comprises:
reacting compounds of Formula 13 with compounds of Formula 19
(Formula Removed)
Formula 13
to form compounds of Formula 22. 10. A method for preparing compounds of Formula 25,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy, R3 and X1 are the same as defined in claim 1, which method comprises:
(a) reacting compounds of Formula 23 with compounds of Formula R3SO2C1
(Formula Removed)
to form compounds of Formula 24
(Formula Removed)
(b) deprotecting compounds of Formula 24 to form compounds of Formula
25.
11. A method for preparing compounds of Formula 29,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy, X1 and R3 are the same as defined in claim 1, which method comprises:
(a) deprotecting compounds of Formula 26
(Formula Removed)
to form compounds of Formula 27;
(Formula Removed)
(b) reacting compounds of Formula 27 with compounds of Formula R3NCO
to form compounds of Formula 28;
(Formula Removed)
(c) deprotecting compounds of Formula 28 to form compounds of Formula 29.
12. A method for preparing compounds of Formula 29,
(Formula Removed)
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereo isomers, prodrugs, metabolites and N-oxide thereof, wherein:
Cy, X1 and R3 are the same as defined in claim 1, which method comprises:
(a) reacting compounds of Formula 27 with phenyl chloroformate
(Formula Removed)
to form compounds of Formula 27a;
(b) reacting compounds of Formula 27a with compounds of Formula R3NH2
(Formula Removed)
to form compounds of Formula 28;
(c) deprotecting compounds of Formula 28 to form compounds of Formula 29.