Resources Contact Us Home
Browse by: INVENTOR PATENT HOLDER PATENT NUMBER DATE
 
 
Phenethanolamine derivatives for treatment of respiratory diseases
RE44874 Phenethanolamine derivatives for treatment of respiratory diseases
Patent Drawings:

Inventor: Box, et al.
Date Issued: April 29, 2014
Application:
Filed:
Inventors:
Assignee:
Primary Examiner: Witherspoon; Sikarl
Assistant Examiner:
Attorney Or Agent: Finnegan, Henderson, Farabow, Garrett & Dunner, LLP
U.S. Class: 564/38; 564/194; 564/86
Field Of Search: ;564/38; ;564/86; ;564/194; ;514/357; ;514/408; ;514/538; ;514/553; ;514/567; ;514/602; ;514/630
International Class: C07C 273/00; C07C 303/00; C07C 233/00; A61K 31/00
U.S Patent Documents:
Foreign Patent Documents: 2140800; 3513885; 3524990; 4028398; 69715; 0069715; 162576; 220054; 220878; 223410; 0 286 242; 0286242; 303465; 0 317 206; 0317206; 0416951; 223671; 0401966; 0947498; 1425001; 2064336; 2129691; 2 140 800; 2140800; 2159151; 2162842; 2169265; 2176476; 2178965; 2230523; 2242134; 95/01170; WO 95/01170; 95/19336; WO 95/19336; 99/16766; WO99/16766; 99/47505; WO99/47505; WO 00/51599; 01/04118; WO 01/04118; 01/13953; WO 02/066422; WO 02/070490; WO 03/024439; 2004/71388; WO 2004/071388
Other References: US. Appl. No. 11/566,346, non-final rejection dated Feb. 11, 2008. cited by applicant.
U.S. Appl. No. 11/566,346, Response to non-final rejection dated Apr. 17, 2008. cited by applicant.
U.S. Appl. No. 11/566,346, Terminal Disclaimer filed Apr. 17, 2008. cited by applicant.
Robert Nett, et al., "Enantioselective synthesis of salmeterol via asymmetric borane reduction"Tetrahedron Letters; 1994; vol. 35, No. 50. cited by applicant.
U.S. Appl. No. 11/207,967, filed Aug. 19, 2005. cited by applicant.
U.S. Appl. No. 11/207,967, final office action dated Jun. 19, 2007. cited by applicant.
U.S. Appl. No. 11/426,657, non-final office dated Jun. 25, 2007. cited by applicant.
U.S. Appl. No. 11/207,967, non-final office action dated Jan. 11, 2007. cited by applicant.
U.S. Appl. No. 11/426,661, non-final office action dated Jan. 12, 2007. cited by applicant.
U.S. Appl. No. 11/426,661, non-final office action dated Jul. 5, 2007. cited by applicant.
U.S. Appl. No. 11/426,657, non-final office action dated Jan. 12, 2007. cited by applicant.
Thornber "Isosterism and molecular modification in drug design" Chemical Society Reviews; 8(4) 563-580, (1979). cited by applicant.
U.S. Appl. No. 10/522,321, filed Jul. 6, 2005. cited by applicant.
U.S. Appl. No. 11/207,667, filed Aug. 19, 2005. cited by applicant.
U.S. Appl. No. 11/426,657, filed Jun. 27, 2006. cited by applicant.
U.S. Appl. No. 11/426,661 filed Jun. 27, 2006. cited by applicant.
Official Action, date mailed Mar. 15, 2007, U.S. Appl. No. 10/522,321. cited by applicant.
Fuji et al., "Novel phosphodiesterase 4 Inhibitor T-440 reverses and prevents human bronchial contraction induced by allergen" J. Pharmacol Exp Ther 284(1): 162(1998). cited by applicant.
Landells et al. "Oral administration of the phosphodiesterase (PDE)4 inhibitor. V11294A Inhibits ex-vivo agonist-induced-cell-activation" Eur Resp J (annu Cong Eur Resp Soc. Geneva) 12(Suppl 28) Abst P2393 (Sep. 1998). cited by applicant.
McHale et al. "Expressin of human recombinant cAMP phosphodiesterase isozyme IV reverses growth arrest phenotypes in phosphodiesterase-deficient yeast." Molec. Pharmacol. Sci. 39; vol. 39; pp. 109-113 (1991). cited by applicant.
Nicholson et al, "Differential modulation of tissue function and therapeutic potential of selective inhibitors of cyclic nucleotide phosphodiesterase isoenzymes." Trends Pharmacol Sci 12: 19-27(1991). cited by applicant.
Torphy et al., "Role of cyclic nucleotide phosphodiesterase isozymes in intact canine trachealis" Mol. Pharmacol. 39:376-384 (1991). cited by applicant.
Dr. Meyer Magarici; Riesgossobre broncodilatadors; SVMS; Nov. 29, 2005. cited by applicant.
Drug Bank Chemical Compound Query Result Re Salmeterol; Jul. 31, 2000. cited by applicant.
D. Iakovidis, et al."Synthesis and beta-andrenoceptor agonist properties of (+/-)-1-(3',4'-dihydroxyphenoxy)-3-(3'',4''-dimethooxyphenyl)ethylamin- o-2-propanol hydrochloride, (+/-)-(RO363.HCl, and the (2S)-(-)-isomer"; European Journal of MedicinalChemistry; Jun 6, 1999; vol. 34, No. 6, pp. 539-548. cited by applicant.









Abstract: The present invention relates to novel compounds of formula (I), to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use in the prophylaxis and treatment of respiratory diseases ##STR00001##
Claim: The invention claimed is:

1. A compound of formula (I) ##STR00023## or a salt.[., solvate, or physiologically functional derivative.]. thereof, wherein: m is an integer of from 2 to 8; n isan integer of from 2 to 5; with the proviso that m+n is 4 to 10; R.sup.1 is selected from hydrogen, C.sub.1-6alkyl, hydroxy, halo, C.sub.1-6haloalkyl, --XC(O)NR.sup.9R.sup.10, --XNR.sup.8C(O)R.sup.9, --XNR.sup.8C(O)NR.sup.9R.sup.10,--XNR.sup.8SO.sub.2R.sup.9, --XSO.sub.2NR.sup.11R.sup.12, .[.XNR.sup.8SO.sub.2R.sup.9R.sup.10,.]. --XNR.sup.9R.sup.10, XN.sup.+R.sup.8R.sup.9R.sup.10, --XNR.sup.8C(O)OR.sup.9, --XCO.sub.2R.sup.9, --XNR.sup.8C(O)NR.sup.8C(O)NR.sup.9R.sup.10, --XSR.sup.9,XSOR.sup.9, and --XSO.sub.2R.sup.9; or R.sup.1 is selected from --X-aryl, --X-hetaryl, and --X-(aryloxy), each optionally substituted by 1 or 2 groups independently selected from hydroxy, C.sub.1-6alkoxy, halo, C.sub.1-6alkyl, C.sub.1-6haloalkyl,--NHC(O)(C.sub.1-6alkyl), --SO.sub.2(C.sub.1-6alkyl), --SO.sub.2(aryl), --SO.sub.2NH.sub.2, --SO.sub.2NH(C.sub.1-6alkyl), --SO.sub.2NH(C.sub.3-7cycloalkyl), --CO.sub.2H, --CO.sub.2(C.sub.1-6alkyl), --SO.sub.2NH(C.sub.3-7cycloalkylC.sub.1-6alkyl),--NH.sub.2, --NH(C.sub.1-6alkyl), or hetaryl optionally substituted by 1 or 2 groups independently selected from hydroxy, C.sub.1-6alkoxy, halo, C.sub.1-6alkyl, or C.sub.1-6haloalkyl; X is --(CH.sub.2).sub.p-- or C.sub.2-6 alkenylene; p is an integerfrom 0 to 6, R.sup.8 and R.sup.9 are independently selected from hydrogen, C.sub.1-6alkyl, C.sub.3-7cycloalkyl, aryl, hetaryl, hetaryl(C.sub.1-6alkyl)- and aryl(C.sub.1-6alkyl)- and R.sup.8 and R.sup.9 are each independently optionally substituted by 1or 2 groups independently selected from halo, C.sub.1-6alkyl, C.sub.1-6haloalkyl, --NHC(O)(C.sub.1-6alkyl), --SO.sub.2(C.sub.1-6alkyl), --SO.sub.2(aryl), --CO.sub.2H, --CO.sub.2(C.sub.1-4alkyl), --NH.sub.2, --NH(C.sub.1-6alkyl), aryl(C.sub.1-6alkyl)-,aryl(C.sub.2-6alkenyl)-, aryl(C.sub.2-6alkynyl)-, hetaryl(C.sub.1-6alkyl)-, --NHSO.sub.2aryl, --NH(hetarylC.sub.1-6alkyl), --NHSO.sub.2hetaryl, --NHSO.sub.2(C.sub.1-6alkyl), --NHC(O)aryl, or --NHC(O)hetaryl: R.sup.10 is selected from hydrogen,C.sub.1-6alkyl and C.sub.3-7cycloalkyl; R.sup.11 and R.sup.12 are independently selected from hydrogen, C.sub.1-6alkyl, C.sub.3-7cycloalkyl, aryl, hetaryl, hetaryl(C.sub.1-6alkyl)- and aryl(C.sub.1-6alkyl)-, or R.sup.11 and R.sup.12,together with thenitrogen to which they are bonded, form a 5-, 6-, or 7-membered nitrogen containing ring; and .sup.R.sup.11 and R.sup.12 are each optionally substituted by one or two groups independently selected from halo, C.sub.1-6alkyl, and C.sub.1-6haloalkyl; where R.sup.1 is --XNR.sup.8C(O)NR.sup.9R.sup.10, R.sup.8 and R.sup.9 may, together with the --NC(O)N-- portion of the group R.sup.1 to which they are bonded, form a 5-, 6- or 7-membered saturated or unsaturated ring; where R.sup.1 is--XNR.sup.8C(O)OR.sup.9, R.sup.8 and R.sup.9 may, together with the --NC(O)O-- portion of the group R.sup.1 to which they are bonded, form a 5-, 6- or 7-membered saturated or unsaturated ring; where R.sup.1 is --XC(O)NR.sup.9R.sup.10 or--XNR.sup.8C(O)NR.sup.9R.sup.10, R.sup.9 and R.sup.10 may, together with the nitrogen to which they are bonded, form a 5-, 6-, or 7-membered nitrogen containing ring; R.sup.2 is selected from hydrogen, hydroxy, C.sub.1-6alkyl, C.sub.1-6alkoxy, halo,aryl, aryl(C.sub.1-6alkyl)-, C.sub.1-6haloalkoxy, and C.sub.1-6 haloalkyl; R.sup.3 is selected from hydrogen, hydroxy, C.sub.1-6alkyl, C.sub.1-6alkoxy, halo, aryl, aryl(C.sub.1-6alkyl)-, C.sub.1-6haloalkoxy, and C.sub.1-6haloalkyl; R.sup.4 and R.sup.5are independently selected from hydrogen and C.sub.1-4 alkyl with the proviso that the total number of carbon atoms in R.sup.4 and R.sup.5 is not more than 4; and, R.sup.6 and R.sup.7 are independently selected from hydrogen and C.sub.1-4alkyl with theproviso that the total number of carbon atoms in .[.R.sup.4 and R.sup.5is.]. .Iadd.R.sup.6 and R.sup.7 is .Iaddend.not more than 4.

2. A compound of formula (I) ##STR00024## or a salt.[., solvate, or physiologically functional derivative.]. thereof, wherein: m is an integer of from 2 to 8; n is an integer of from 2 to 5; with the proviso that m+n is 4 to 10; R.sup.1 isselected from hydrogen, C.sub.1-6alkyl, hydroxy, halo, C.sub.1-6haloalkyl, --XC(O)NR.sup.9R.sup.10, --XNR.sup.8C(O)R.sup.9, --XNR.sup.8C(O)NR.sup.9R.sup.10, --XNR.sup.8SO.sub.2R.sup.9, --XSO.sub.2NR.sup.11R.sup.12.[.;.]..Iadd.,.Iaddend.--XNR.sup.9R.sup.10, --XNR.sup.8C(O)OR.sup.9, or R.sup.1 is selected from --X-aryl, --X-hetaryl, or --X-(aryloxy), each optionally substituted by 1 or 2 groups independently selected from hydroxy, C.sub.1-6alkoxy, halo, C.sub.1-6alkyl,C.sub.1-6haloalkyl, --NHC(O)(C.sub.1-6alkyl), --SO.sub.2(C.sub.1-6alkyl), --SO.sub.2(aryl), --SO.sub.2NH.sub.2, --SO.sub.2NH(C.sub.1-6alkyl), --SO.sub.2NH(C.sub.3-7cycloalkyl), --CO.sub.2H, --CO.sub.2(C.sub.1-6alkyl),--SO.sub.2NH(C.sub.3-7cycloalkylC.sub.1-6alkyl), --NH.sub.2, --NH(C.sub.1-6alkyl), or hetaryl optionally substituted by 1 or 2 groups independently selected from hydroxy, C.sub.1-6alkoxy, halo, C.sub.1-6alkyl, or C.sub.1-6haloalkyl; X is--(CH.sub.2).sub.p-- or C.sub.2-6 alkenylene; p is an integer from 0 to 6.[.,.]..Iadd.; .Iaddend. R.sup.8 and R.sup.9 are independently selected from hydrogen, C.sub.1-6alkyl, C.sub.3-7cycloalkyl, aryl, hetaryl, hetaryl(C.sub.1-6alkyl)- andaryl(C.sub.1-6alkyl)- and R.sup.8 and R.sup.9 are each independently optionally substituted by 1 or 2 groups independently selected from halo, C.sub.1-6alkyl, C.sub.1-6haloalkyl, --NHC(O)(C.sub.1-6alkyl), --SO.sub.2(C.sub.1-6alkyl), --SO.sub.2(aryl),--CO.sub.2H, and --CO.sub.2(C.sub.1-4alkyl), --NH.sub.2, --NH(C.sub.1-6alkyl), aryl(C.sub.1-6alkyl)-, aryl(C.sub.2-6alkenyl)-, aryl(C.sub.2-6alkynyl)-, hetaryl(C.sub.1-6alkyl)-, --NHSO.sub.2aryl, --NH(hetarylC.sub.1-6alkyl), --NHSO.sub.2hetaryl,--NHSO.sub.2(C.sub.1-6alkyl), --NHC(O)aryl, or --NHC(O)hetaryl: R.sup.10 is selected from hydrogen, C.sub.1-6alkyl and C.sub.3-7cycloalkyl; R.sup.11 and R.sup.12 are independently selected from hydrogen, C.sub.1-6alkyl, C.sub.3-7cycloalkyl, aryl,hetaryl, hetaryl(C.sub.1-6alkyl)- and aryl(C.sub.1-6alkyl)-, or R.sup.11 and R.sup.12, together with the nitrogen to which they are bonded, form a 5-, 6-, or 7-membered nitrogen containing ring; and R.sup.11 and R.sup.12 are each optionally substitutedby one or two groups independently selected from halo, C.sub.1-6alkyl, and C.sub.1-6haloalkyl; where R.sup.1 is --XNR.sup.8C(O)NR.sup.9R.sup.10, R.sup.8 and R.sup.9 may, together with the portion --NC(O)N-- of the group R.sup.1 to which they are bonded,form a 5-, 6-, or 7-membered saturated or unsaturated ring; where R.sup.1 is --XNR.sup.8C(O)OR.sup.9, R.sup.8 and R.sup.9 may, together with the portion --NC(O)O-- of the group R.sup.1 to which they are bonded, form a 5-, 6-, or 7-membered saturated orunsaturated ring; where R.sup.1 is --XC(O)NR.sup.9R.sup.10 or --XNR.sup.8C(O)NR.sup.9R.sup.10, R.sup.9 and R.sup.10 may, together with the nitrogen to which they are bonded, form a 5-, 6-, or 7-membered nitrogen containing ring; R.sup.2 is selectedfrom hydrogen, hydroxy, C.sub.1-6alkyl, C.sub.1-6alkoxy, halo, aryl, aryl(C.sub.1-6alkyl)-, C.sub.1-6haloalkoxy, and C.sub.1-6 haloalkyl; R.sup.3 is selected from hydrogen, hydroxy, C.sub.1-6alkyl, C.sub.1-6alkoxy, halo, aryl, aryl(C.sub.1-6alkyl)-,C.sub.1-6haloalkoxy, and C.sub.1-6haloalkyl; R.sup.4 and R.sup.5 are independently selected from hydrogen and C.sub.1-4 alkyl with the proviso that the total number of carbon atoms in R.sup.4 and R.sup.5 is not more than 4; and, R.sup.6 and R.sup.7 areindependently selected from hydrogen and C.sub.1-4alkyl with the proviso that the total number of carbon atoms in R.sup.4 and R.sup.5 is not more than 4.

3. A compound according to claim 1 of formula (Ia) ##STR00025## or a salt.[., solvate, or physiologically functional derivative.]. thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.6 and R.sup.7 are as defined for claim 1 and m is 4 or 5.

4. A compound .[.according to any one of claims 1 to 3.]. which is selected from .Iadd.the group consisting of.Iaddend.: N-{3-[(2-{[6-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}--amino)hexyl]oxy}ethoxy)methyl]phenyl}-N'-phenylurea; 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol; N-(3-{[({3-[(2-{[6-({(2R)-2-Hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]-ethyl}-amino)hexyl]oxy}ethoxy)methyl]phenyl}amino)carbonyl]amino}phenyl)py- ridine-3-carboxamide; 4-{(1R)-1-Hydroxy-2-[(6-{2-[(3-hydroxybenzyl)oxy]ethoxy}hexyl)amino]ethyl- }-2-(hydroxymethyl)phenol; 4-{(1R)-2-[(6-{2-[(3,5-Dimethylbenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol; N-{3-[(2-{[5-({(2R)-2-Hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}- amino)pentyl]oxy}ethoxy)methyl]phenyl}-N'-phenylurea; and salts.[.,solvates, and physiologically functional derivatives.]. thereof.

5. A pharmaceutical formulation comprising a compound according to claim 1 or a pharmaceutically acceptable salt.[., solvate, or physiologically functional derivative.]. thereof, and a pharmaceutically acceptable carrier or excipient, andoptionally one or more other therapeutic ingredients.

6. A combination comprising a compound according to claim 1 or a pharmaceutically acceptable salt.[., solvate, or physiologically functional derivative.]. thereof, and one or more other therapeutic ingredients.

7. A combination according to claim 6 wherein the other therapeutic ingredient is .Iadd.selected from the group consisting of .Iaddend.a PDE4 inhibitor, a corticosteroid .[.or.]. .Iadd.and .Iaddend.an anti-cholinergic agent.

8. A combination according to claim 7 wherein the additional therapeutic ingredient is 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11 .beta.-hydroxy-16.alpha.-methyl-3-oxo-androsta-1,4-diene-17.beta.-carboth- ioic acidS-fluoromethyl ester.

9. A method for the .[.prophylaxis or.]. treatment of a clinical condition in a mammal, for which a selective .beta..sub.2-adrenoreceptor agonist is indicated, which comprises administering a therapeutically effective amount of a compoundaccording to claim 1, or a pharmaceutically acceptable salt.[., solvate, or physiologically functional derivative.]. thereof.

10. A process for preparing a compound as defined according to .[.any one of claims 1 to 3.]. .Iadd.claim 1.Iaddend., wherein said process is one of (A), (B).Iadd., .Iaddend.or (C): (A) deprotecting a protected intermediate of formula (II):##STR00026## or a salt .[.or solvate.]. thereof, wherein R.sup.4, R.sup.5, R.sup.6, R.sup.7, m, and n are as defined for the compound of formula (I) or (Ia), and .[.R.sup.1.alpha., R.sup.2.alpha., and R.sup.3.alpha..]. .Iadd.R.sup.1a, R.sup.2a, andR.sup.3a.Iaddend. are each independently either the same as R.sup.1, R.sup.2, and R.sup.3 respectively as defined for the compound of formulae (I) or (Ia) or a precursor for said group R.sup.1, R.sup.2, or R.sup.3, and R.sup.13, R.sup.14, and R.sup.15are each independently either hydrogen or a protecting group provided that at least one of R.sup.13, R.sup.14, and R.sup.15 is a protecting group, and R.sup.19 is hydrogen or a protecting group; (B) alkylating an amine of formula (XIX): ##STR00027##wherein R.sup.13, R.sup.14, R.sup.15 and R.sup.19 are as hereinbefore defined, with a compound of formula (VI): ##STR00028## wherein L.sup.1 represents a leaving group such as halo, and removing any protecting groups present on the alkylated compound; and (C) reacting an amine of formula (XIX) as defined hereinabove, with a compound of formula (XX): ##STR00029## wherein R.sup.4, R.sup.6, R.sup.7, .[.R.sup.1.alpha., R.sup.2.alpha., and R.sup.3.alpha..]. .Iadd.R.sup.1a, R.sup.2a, R.sup.3a, .Iaddend. mand n are as hereinbefore defined; under conditions suitable to effect reductive amination, wherein any one of (A), (B), or (C) may optionally employ one or more of the following steps in any order: (i) removing any protecting groups; (ii) separatingan enantiomer or diastereoisomer from a mixture of enantiomers or diastereoisomers; (iii) converting the product to a corresponding salt.[., solvate, or physiologically functional derivative.]. thereof.[...]..Iadd.; .Iaddend. (iv) converting a group.[.R.sup.1.alpha., R.sup.2.alpha., and/or R.sup.3.alpha..]..Iadd.R.sup.1a, R.sup.2a and/or R.sup.3a.Iaddend. to a group R.sup.1, R.sup.2 and/or R.sup.3 respectively.

11. A compound .[.of formula (I).]. according to claim 1 wherein the group R.sup.1 is attached to the meta-position relative to the --OCR.sup.6R.sup.7--link.

12. A compound .[.of formula (I).]. according to claim 1, wherein the groups R.sup.2 and R.sup.3 are each independently attached to the ortho position relative to the --OCR.sup.6R.sup.7-- link.

13. A compound .[.of formula (I).]. according to claim 3 wherein R.sup.1 represents a substituent other than hydrogen, attached to the meta-position relative to the --OCR.sup.6R.sup.7-- link, and R.sup.2 and R.sup.3 each represent hydrogen.

14. A compound .[.of formula (I).]. according to claim 1 wherein R.sup.1 represents hydrogen and R.sup.2 and R.sup.2 each represent a substituent at least one of which is other than hydrogen, and R.sup.2 and R.sup.3 are each independentlyattached to the ortho- or meta-positions relative to the --OCR.sup.6R.sup.7-- link.

15. A compound .[.of formula (I).]. according to claim 1 wherein R.sup.1 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, hydroxy, halo, C.sub.1-6haloalkyl, --XNR.sup.8(C)OR.sup.9, --XNR.sup.8C(O)NR.sup.9R.sup.10,--XNR.sup.8SO.sub.2R.sup.9, --XSO.sub.2NR.sup.11R.sup.12, --XNR.sup.9R.sup.10, --XNR.sup.8C(O)OR.sup.9, XSR.sup.9, XSOR.sup.9, XSO.sub.2R.sup.9, X-aryl, X-hetaryl and X-aryloxy.

16. A compound .[.of formula (I).]. according to claim 1 wherein X is (CH.sub.2).sub.p and p is zero.

17. A compound .[.of formula (I).]. according to claim 1 wherein R.sup.1 .[..sup.is selected from the group consisting of hydrogen, c.sub.1-4alkyl,.]. .Iadd.is selected from the group consisting of C.sub.1-4alkyl, .Iaddend.hydroxy, halo,--NR.sup.8C(O)NR.sup.9R.sup.10, and --NR.sup.8SO.sub.2R.sup.9.

18. A compound .[.of formula (I).]. according to claim 1, wherein R.sup.2 and R.sup.3 are independently selected from the group consisting of hydrogen, halogen, haloC.sub.1-6alkyl, C.sub.1-6alkyl, phenyl, and substituted phenyl.

19. A compound .[.of formula (I).]. according to claim 1, wherein R.sup.4 and R.sup.5 are independently selected from the group consisting of hydrogen.[.,.]. and methyl.

20. A compound .[.of formula (I).]. according to claim 1, wherein R.sup.6 and R.sup.7 are independently selected from the group consisting of hydrogen.[.,.]. and methyl.

21. A compound .[.of formula (I).]. according to claim 1, wherein m is 4, 5, or 6, and n is 2 or 3.

22. An inhalation device comprising the compound according to claim 1.

23. An inhalation device according to claim 22, wherein the compound is present in particles ranging in size from 1 .mu.m to 10 .mu.m.

24. An inhalation device according to claim 22, wherein the compound is present in a dry powder pharmaceutical formulation.

25. An inhalation device according to claim 22, wherein the compound is present in an aerosol pharmaceutical formulation.

.Iadd.26. A compound which is selected from the group consisting of: N-{3-[(2-{[6-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}- -amino)hexyl]oxy}ethoxy)methyl]phenyl}-N'-phenylurea; 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol; and salts thereof. .Iaddend.

.Iadd.27. A compound which is selected from the group consisting of: 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol; N-(3-{[({3-[(2-{[6-({(2R)-2-Hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]- ethyl}-amino)hexyl]oxy}ethoxy)methyl]phenyl}amino)carbonyl]amino}phenyl)py- ridine-3-carboxamide; and salts thereof. .Iaddend.

.Iadd.28. A compound which is selected from the group consisting of: 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol; 4-{(1R)-1-Hydroxy-2-[(6-{2-[(3-hydroxybenzyl)oxy]ethoxy}hexyl)amino]ethyl- }-2-(hydroxymethyl)phenol; and salts thereof. .Iaddend.

.Iadd.29. A compound which is selected from the group consisting of: 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol; 4-{(1R)-2-[(6-{2-[(3,5-Dimethylbenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol; and salts thereof. .Iaddend.

.Iadd.30. A compound which is selected from the group consisting of: 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyet- hyl}-2-(hydroxymethyl)phenol; N-{3-[(2-{[5-({(2R)-2-Hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}- amino)pentyl]oxy}ethoxy)methyl]phenyl}-N'-phenylurea; and salts thereof. .Iaddend.
Description:
 
 
  Recently Added Patents
RF amplifier with digital filter for polar transmitter
Milk frother
Optical fixing device and image forming apparatus
Display device and method of manufacturing the same
Plants and seeds of hybrid corn variety CH424126
Flat panel crystal display employing simultaneous charging of main and subsidiary pixel electrodes
Evolutionary clustering algorithm
  Randomly Featured Patents
Retainer ring and splined member assembly
Method for the fermentative production of D-pantothenic acid by enhancement of the panD gene in microorganisms
Electrical connector housing
Spout
Exhaust hood for a rotisserie oven
Temperature stable and sunlight protected photochromic articles
Toner for electrostatic image development
Circuit interrupting apparatus and method for high current power lines
Comparator
Transducer power dissipation control in a thermal ink jet printhead