http://rdf.ncbi.nlm.nih.gov/pubchem/patent/AR-065355-A1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_f2d3599fb8f8f479dba95ca9bb504884 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-426 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-4535 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P29-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-423 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P17-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P35-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P19-02 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P17-10 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P43-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P1-02 |
| filingDate | 2008-02-14-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationDate | 2009-06-03-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | AR-065355-A1 |
| titleOfInvention | MODULATORS OF LTA4H AND ITS USES |
| abstract | Leukotrin A4 hydrolase inhibitors (LTA4H), the compositions containing them, and the methods of use to inhibit the activity of a LTA4H enzyme and the treatment, prevention or inhibition of inflammation or conditions and diseases associated with inflammation. Claim 1: A method of treating or preventing a condition mediated by LTA4H in a subject, comprising administering to the subject a at least a therapeutically effective amount of at least one LTA4H modulator selected from the compounds of formula (1): wherein X is selected from group consisting of NR5, O, and S, and R5 is one of H and CH3; Y is selected from the group consisting of CH2, and O; Z is selected from the group consisting of O and the link; W is selected from the group consisting of CH2 and CHR1 -CH2, in which R1 is one of H and OH, where the carbon component R1-linked in said CHR1-CH2 does not bind directly to the nitrogen component to which said W is linked ; R4 is selected from the group consisting of H, OCH3, CI, F, Br, I, OH, NH2, CN, CF3 and CH3; R6 is H or F; and R2 and R3 are each independently selected from the group consisting of: A) H, C1-7alkyl, C3-7alkenyl, in which the carbon in that alkenyl. which is linked to the nitrogen component only has single bonds, C3-7alkyl, where the carbon in that alkynyl that is linked to the nitrogen component only has single bonds, C3-7 optionally benzyl-fused alkyl, C5-7cycloalkenyl, -C3-7cycloalkylC1-7alkyl, -C1-7alkylC3-7cycloalkyl and phenyl, where each of the substituents A) is independently substituted with 0, 1, or 2 Rq, and each of the Rq is a substituent of the carbon component which is at least one carbon-removed component of the nitrogen component; B) a HetRa substituent; C) -C1-7alkylC (O) Rx, optionally substituted by CH2Rar or CH2Rar '; D) -C2-5alkylC (O) Rx, where the carbon components of two valencies allowed in the C2-5alkyl of that -C2-5alkylC (O) Rx are part of a C3-6 saturated carbocycle; E) -C2-5alkyl where the carbon components of two valencies allowed in the C2-5alkyl of that -C2-5alkylOH are part of a saturated C3-6carbocycle; E) -C0-4alkylphenyl, where the phenyl that -C0-4alkylphenyl is fused into two adjacent carbon components in that phenyl to Rf, or benzofusiona; G) -C0-4alkylAr6, where Ar6 is a 6-component heteroaryl that has a bond point in a carbon component and has one -N-ears = heteroatom components, and benzofused; H) -C0-4alkylAr5, where Ar5 is a 5-component heteroaryl with a heteroatom component selected from the group consisting of O, S, and> NRy, and having 0 or 1 -N = additional heteroatom component, which optionally contains two groups carbonyls, and is optionally benzofused; I) -C1-4alkylAr5 ', where Ar5' is a 5-component heteroaryl containing 3 or 4 nitrogen components, optionally substituted by Ry, and with a permissible valence site as a binding point; J) -C0-4alkylAr6-6, where Ar6-6 is a phenyl linked to C0-4alkyl that is fused at sites of permitted valence to a 6-component heteroaryl, where the 6-component heteroaryl has one or two -N = components heteroatoms; K) -C0-4alkyl6-5, where Ar6-5 is a phenyl linked to C0-4alkyl that is fused at sites of valence allowed to a 5-component heteroaryl, said 5-component heteroaryl having a heteroatomoselected component of the group consisting of O, S, and> NRy, and the 5-component heteroaryl with 0 or 1 additional heteroatom component that is -N =; and L) one of 2- (4-ethyl-phenoxy) -benzothiazole, 2- (4-ethyl-phenoxy) -benzoxazole, and 2- (4-ethyl-phenoxy) -1H-benzoimidazole; M) SO2C1-4alkyl; alternatively R2 and R3 are taken together with the nitrogen to which they are linked to form a heterocyclic ring containing at least one heteroatom component that is the bound nitrogen, the heterocyclic ring is selected from the group consisting of: i) a heterocyclic HetRb ring of 4 to 7 components, this 4 to 7 component HetRb heterocyclic ring has a heteroatom compound that is bound nitrogen, substituted by 0, 1, or 2 substituents on the same or different substitution components, these substituents are selected from the group consisting of - Ry, -CN, -C (O) Ry, -C0-4alkylCO2Ry, -C0-4alkylC (O) CO2Ry, -C0-4alkylORy, -C0-4alkylC (O) NRyRz, -C0-4alkylNRyC (O) Rz, - C (O) NRzORy, -C0-4alkylNRyC (O) CH2ORy, -C0-4alkylNRyC (O) CH2C (O) Ry, -C0-4alkylNRyCO2Ry, -C0-4alkylNRyC (O) NRyRz, -C0-4alkylNRyC (S) NRyRz , -NRyC (O) CO2Ry, -NRyRz, -C0-4alkylNRwSO2Ry, 1,3-dihydro-indole-2-one-1-yl, 1,3-dihydro-benzoimidazol-2-one-1-yl, tetrazol- 5-iI, 1 -Ry-1H-tetrazol-5-yl , Ry-triazolyl, 2-Ry-2H-tetrazol-5-yl, pyrrolidin-2-thione-1-yl, piperidin-2-thione-1-yl, -C0-4alkyl (O) N (Ry) (SO2Ry ), -C0-4alkyl (Ry) (SO2) NRyRy, -C0-4alkylN (Ry) (SO2) NRyCO2Ry, halo, or a group of formulas (2); ii) a 5 to 7 component HetRc heterocyclic ring, this 5 to 7 component HetRc heterocyclic ring has an additional heteroatom compound separated from the nitrogen linked by at least one carbon component, the additional heteroatom component selected from the group consisting of O, S (= O) 0-2, and> NRm, the 5 to 7 component heterocyclic HetRc ring has 0 or 1 carbonyl component, and is substituted with 0, 1 or 2 substituents on the same or different carbon substitution components, these substituents selected from the group consisting of -C (O) Ry, -CO2Ry -C3-4alkylCO2Ry and Rz iii) one of imidazolidine-1-yl, 2-imidazoline-1-yl, pyrazol-1-yl, imidazol-1-yl , 2H-tetrazol-2-yl, 1H-tetrazol-1-yl, pyrrole-1-yl, 2-pyrroline-1-yl, and 3-pyrroline-1-yl, where each 2H-tetrazol-2-yl and 1H-tetrazol-1-yl is substituted on the carbon component with 0 or 1 of C0-4a-alkylRz, -C0-4alkylSRy, -C0-4alkyl2Ry, and substituent HetRa; and iv) one of 1,2,3,4-tetrahydro-quinolin-1-yl, 1,2,3,4-tetrahydro-isoquinoline-2-iI, indole-1-yl, isoindol-2-iI, indoline -1-yl, benzimidazol-1-yl, 2,8-diazaspiro [4.5] decan-1-one-8-iI, 4 - {[(2-tert-butoxycarbonylamino-cyclobutanecarbonyl) -amino] -methyl} -piperidine -1-yl, 4 - {[(2-amino-cyclobutanecarbonyl) -amino] -methyl} -piperidin-1-yl, 3,9-diazaspiro [5.5] tert-butyl ester -9-yl of undecano-3- acid carboxylic 4-oxo-1-phenyl-1,3,8-triazaspiro [4.5] dec-8-iI, and 4-oxo-1,3,8-triazaspiro [4.5] dec-8-yl; wherein the HetRa substituent is a 4 to 7 component heterocyclic ring with a carbon component bond point and containing a component> NRm as a heteroatom component, and the heteroatom component is separated from the carbon component link point by at least 1 additional carbon component; Rk is selected from the group consisting of H, -C1-4aIkyl, -C0-4alkylRRA each being optionally substituted with 1, 2, or 3 Rn substituents; Rl is selected from the group consisting of -CO2Rs and -C (O) NRsRs' RM is selected from the group consisting of Rz, indole-7-yl, -SO2Ry, -C3-4alkylCO2Ry, -CO2Ry, C (O) NRzORy, -C (O) Ry, -C (O) C1-4alkylORy, -C0-4alkylC (O) NRsRs, C0-4alkylC (O) CO2Ry, 1,3-dihydro-indole-2-one-1-yl, 1,3 -dihydro-benzoimidazol-2-one-1-yl, tetrazol-5-yl, 1-Ry-1H-tetrazol-5-yl, Ry-triazoliI, 2-Ry-2H-tetrazol-5-yl and -C0- 4-alkylC (O) N (Ry) (SO2Ry), each being optionally substituted with 1, 2 or 3 Rn substituents; Rn is selected from the group consisting of OCH3, CI, F, Br, I, OH, NH2, CN, CF3, CH3, OC (O) CH3, and NO2; Rp is selected from the group consisting of Ry, -C2-4alkylORy, RAr, -C1-2alkylCO2Ry, -C1-2aIquiICONRsRs', indole-7-yl, and -SO2C1-4alkyl; Rq is selected from the group consisting of fluoro, chloro, bromo, iodo, trifluoromethyl, trichloromethyl, -CN, -C1-4alkyl, -C0-4alkylRar, -C0-4aIquilRar ', -C0-4alkylORy, -C0-4alkylCO2Ry -C0- 4alkylNRyRz, -C0-4alkylNRyCORy, -C0-4alkylNRyCONRyRz, -C0-4alkylNRySO2Ry, and -C0-4alkylSRy; Rs and Rs' are independently selected from the group consisting of H, -C1-4alkyl, and -C0-4alkylphenyl; alternatively, Rs and Rs 'are taken together with the nitrogen component to which those Rs and Rs' are linked to form a heterocyclic ring of 4 to 7 components having 0 or 1 additional heteroatom component selected from the group consisting of O, S, and > NRy, provided that this additional heteroatom component is separated by at least two carbon components from the nitrogen component to which Rs and Rs' are linked, and provided that where Ry is C0-4alkylRar, Rar is not substituted by Rl; Rw is selected from the group consisting of Ry and -C3-7cycloalkyl; Rx is selected from the group consisting of -ORy, NRyRz, -C1-4alkyl and -C0-4aIquilRar; Ry is selected from the group consisting of H, -C1-4alkyl, C0-4alkylRar and -C0-4alkylRar ', each optionally substituted by 1, 2, or 3 Rn substituents; Rz is selected from the group consisting of Ry, -C2-4alkylORy, -C1-2aC1CO2Ry, -C1-2alkylC (O) NRsRs 'and --C2-4alkylNRsRs'; when Ry and Rz are linked to a nitrogen component, Ry and Rz are selected as set forth above, or Ry and Rz are taken together with the nitrogen component linked with Ry- and Rz- to form a heterocyclic ring HetRd from 4 to 7 components having 0 or 1 additional heteroatom component selected from the group consisting of O, S, and> NRm, that 4 to 7 component heterocyclic HetRd ring has 0 or 1 carbonyl component, and that 4 to 7 component HetRd heterocyclic ring has 0 or 1 carbon component of allowed valence substituted by at least one of Rm, -CO2H, and -C0-1alkylORy; Rar is a molecule with a point of attachment in the carbon component and that molecule is selected from the group consisting of phenyl, pyridyl, pyrimidyl and pyrazinyl, where each carbon component of allowed valence in each of the molecules is independently replaced with at least one of 0,1,2 or 3 Rn, and 0 or 1 Rl; Rar is a ring of 3 to 8 components, which has 0, 1 or 2 heteroatom components selected from the group consisting of O, S, N, and> NRy, with 0, 1, or 2 unsaturated bonds, 0 or 1 carbonyl component, where each component of allowed valence e |
| priorityDate | 2007-02-14-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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Total number of triples: 45.