Methods for treating asthmatic conditions

Amethod of treatment of asthma in a mammal, the method comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of the formula:

• 42
• wherein:
• R is selected from the formulae —(CH2)n—A, —(CH2)n—S—A, or —(CH2)n—O—A, wherein A is selected from the moieties:
• 43
• D is C1-C6 lower alkyl, C1-C6 lower alkoxy, C3-C6 cylcoalkyl, —CF3 or —(CH2)1-3—CF3;
• B and C are independently selected from phenyl, pyridinyl, pyrimidinyl, furyl, thienyl or pyrrolyl groups, each optionally substituted by from 1 to 3, preferably 1 to 2, substituents selected independently from H, halogen, —CN, —CHO, —CF3, —OCF3, —OH, —C1-C6 alkyl, C1-C6 alkoxy, —NH2, —N(C1-C6)2, —NH(C1-C6), —N—C(O)—(C1-C6), —NO2, or by a 5- or 6-membered heterocyclic or heteroaromatic ring containing 1 or 2 heteroatoms selected from O, N or S;
• or
• n is an integer from 0 to 3;
• n1 is an integer from 1 to 3;
• n2 is an integer from 0 to 4;
• n3 is an integer from 0 to 3;
• n4 is an integer from 0 to 2;
• X1 is selected from a chemical bond, —S—, —O—, —S(O)—, —S(O)2—, —NH—, —NHC(O)—, —C═C—,
• 44
• R1 is selected from C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C6 cycloalkyl, tetrahydropyranyl, camphoryl, adamantyl, CN, —N(C1-C6 alkyl)2, phenyl, pyridinyl, pyrimidinyl, furyl, thienyl, napthyl, morpholinyl, triazolyl, pyrazolyl, piperidinyl, pyrrolidinyl, imidazolyl, piperizinyl, thiazolidinyl, thiomorpholinyl, tetrazole, indole, benzoxazole, benzofuran, imidazolidine-2-thione, 7,7,dimethyl-bicyclo[2.2.1]heptan-2-one, Benzo[1,2,5]oxadiazole, 2-Oxa-5-aza-bicyclo[2.2.1]heptane, Piperazin-2-one or pyrrolyl groups, each optionally substituted by from 1 to 3, preferably 1 to 2, substituents independently selected from H, halogen, —CN, —CHO, —CF3, OCF3, —OH, —C1-C6 alkyl, C1-C6 alkoxy, —NH2, —N(C1-C6)2, —NH(C1-C6), —N—C(O)—(C1-C6), —NO2, —SO2(C1-C3 alkyl, —SO2NH2, —SO2NH(C1-C3 alkyl), —SO2N(C1-C3 alkyl)2, —COOH, —CH2—COOH, —CH2—N(C1-C6 alkyl), —CH2—N(C1-C6 alkyl)2, —CH2—NH2, pyridine, 2-Methyl-thiazole, morpholino, 1-Chloro-2-methyl-propyl, —C1-C6thioalkyl, phenyl (further optionally substituted with halogens), benzyloxy, (C1-C3 alkyl)C(O)CH3, (C1-C3 alkyl)OCH3, C(O)NH2, or
• 45
• X2 is selected from —O—, —CH2—, —S—, —SO—, —SO2—, —NH—, —C(O)—,
• 46
• R2 is a ring moiety selected from phenyl, pyridinyl, pyrimidinyl, furyl, thienyl or pyrrolyl groups, the ring moiety being substituted by a group of the formula —(CH2)n4—CO2H or a pharmaceutically acceptable acid mimic or mimetic;
• and also optionally substituted by 1 or 2 additional substituents independently selected from H, halogen, —CN, —CHO, —CF3, —OCF3, —OH, —C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, —NH2, —N(C1-C6)2, —NH(C1-C6), —N—C(O)—(C1-C6), or —NO2;
• R3 is selected from H, halogen, —CN, —CHO, —CF3, —OCF3, —OH, —C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, —NH2, —N(C1-C6)2, —NH(C1-C6), —N—C(O)—(C1-C6), or —NO2;
• R4 is selected from H, halogen, —CN, —CHO, —CF3, —OCF3, —OH, —C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, —NH2, —N(C1-C6)2, —NH(C1-C6), —N—C(O)—(C1-C6), —NO2, —N—C(O)—N(C1-C3 alkyl)2, —N—C(O)—NH(C1-C3 alkyl), —N—C(O)—O—(C1-C3 alkyl), —SO2—C1-C6 alkyl, —S—C3-C6 cycloalkyl, —S—CH2—C3-C6 cycloalkyl, —SO2—C3-C6 cycloalkyl, , —SO2—CH2—C3-C6 cycloalkyl, C3-C6 cycloalkyl, —CH2—C3-C6 cycloalkyl, —O—C3-C6 cycloalkyl, , —O—CH2—C3-C6 cycloalkyl, phenyl, benzyl, benzyloxy, morpholino or other heterocycles such as pyrrolidino, piperidine, piperizine furan, thiophene, imidazole, tetrazole, pyrazine, pyrazolone, pyrazole, imidazole, oxazole or isoxazole, the rings of each of these R4 groups each being optionally substituted by from 1 to 3 substituents selected from the group of H, halogen, —CN, —CHO, —CF3, —OH, —C1-C6 alkyl, C1-C6 alkoxy, —NH2, —N(C1-C6)2, —NH(C1-C6), —N—C(O)—(C1-C6), —NO2, —SO2(C1-C3 alkyl), —SO2NH(C1-C3 alkyl), —SO2N(C1-C3 alkyl)2, or OCF3;
• or a pharmaceutically acceptable salt form thereof.