CCR-3 receptor antagonists

a technology of ccr-3 receptor and antagonist, which is applied in the direction of biocide, amide active ingredients, drug compositions, etc., can solve the problems of side effects, osteoporosis and growth retardation in patients, and achieve the effect of inhibiting the binding of eotaxin

Inactive Publication Date: 2006-07-27
DU BOIS DAISY JOE
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The 1,2-diaminocyclopentane derivatives effectively inhibit eosinophil recruitment, offering a potential alternative to glucocorticoids with fewer side effects, thus providing a therapeutic option for eosinophil-mediated inflammatory diseases like asthma.

Problems solved by technology

However, prolonged use of glucocorticoids can lead to side effects such as glaucoma, osteoporosis and growth retardation in the patients ((see Hanania, N. A. et al., J. Allergy and Clin. Immunol., Vol. 96, 571-579 (1995) and Saha, M. T. et al., Acta Paediatrica, Vol. 86, #2, 138-142 (1997)).

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • CCR-3 receptor antagonists
  • CCR-3 receptor antagonists
  • CCR-3 receptor antagonists

Examples

Experimental program
Comparison scheme
Effect test

example 1

(±)-trans-N-{2-[3-(4-Chlorophenyl)propylamino]cyclopentyl}-2-[5-(3,4-dimethoxyphenyl)pyrimidin-2-ylsulfanyl]acetamide hydrochloride

[0129]

[0130] A solution of (±)-trans-[3-(4-chlorophenyl)propyl]-(2-{2-[5-(3,4-dimethoxyphenyl)pyrimidin-2-ylsulfanyl]acetylamino}cyclopentyl)carbamic acid tert-butyl ester (185 mg, 80% pure, ˜0.23 mmol) in 10% HCl / MeOH (30 mL) was stirred at room temperature overnight. The MeOH was evaporated and the residue was partitioned between CH2Cl2 and saturated NaHCO3. The aqueous phase was extracted with CH2Cl2 and the extracts were washed with brine, dried and concentrated. Purification of the residue by preparative TLC with 10:0.95:0.05 CH2Cl2:MeOH:NH4OH gave the free base (98 mg, 0.18 mmol) as a colorless oil. A solution of the free base in CH2Cl2 was treated with 1 N HCl in Et2O (0.3 mL, 0.3 mmol) and concentrated to give the product (104 mg, 67% from (±)-trans-(2-amino-cyclopentyl)-[3-(4-chloro-phenyl)-propyl]-carbamic acid tert-butyl ester) as a yellow so...

example 2

(±)-trans-N-{2-[3-(4-Chlorophenyl)propylamino]cyclopentyl}-4-methanesulfonylbenzamide hydrochloride

[0142]

[0143] A solution of (±)-trans-[3-(4-chlorophenyl)propyl]-[2-(4-methanesulfonylbenzoylamino)cyclopentyl]carbamic acid tert-butyl ester in 10% HCl / MeOH (25 mL) was stirred at room temperature overnight. The MeOH was evaporated and the residue was partitioned between CH2Cl2 and saturated NaHCO3. The aqueous phase was extracted with CH2Cl2 and the extracts were washed with brine, dried and concentrated. Purification of the residue by preparative TLC with 10:0.95:0.05 CH2Cl2:MeOH:NH4OH gave the free base (116 mg, 0.27 mmol) as a colorless oil. A solution of the free base in CH2Cl2 was treated with 1 N HCl in Et2O (0.3 mL, 0.3 mmol) and concentrated to give the product (123 mg, 61%) as a white solid: mp 192.3-196.8° C.; MS m / z435(M+1)+.

[0144] The intermediate (±)-trans-[3-(4-chlorophenyl)propyl]-[2-(4-methanesulfonylbenzoylamino)cyclopentyl]carbamic acid tert-butyl ester was prepare...

example 3

(±)-trans-1-{2-[3-(4-Chlorophenyl)propylamino]cyclopentyl}-3-(3,4,5-trimethoxyphenyl)urea hydrochloride

[0147]

[0148] A solution of (±)-trans-[3-(4-chlorophenyl)propyl]-{2-[3-(3,4,5-trimethoxyphenyl)-ureido]cyclopentyl}carbamic acid tert-butyl ester (165 mg, 0.29 mmol) in 10% HCl / MeOH (25 mL) was stirred at room temperature overnight. The MeOH was evaporated and the residue was partitioned between CH2Cl2 and saturated NaHCO3. The aqueous phase was extracted with CH2Cl2 and the extracts were washed with brine, dried and concentrated. Purification of the residue by preparative TLC with 10:0.95:0.05 CH2Cl2:MeOH:NH4OH gave the free base as a colorless oil. A solution of the free base in CH2Cl2 was treated with 1 N HCl in Et2O (0.4 mL, 0.4 mmol) and concentrated to give the product (104 mg, 72%) as a tan solid: mp 91.3-96.0° C.; MS m / z 462 (M+1)+.

[0149] The intermediate (±)-trans-[3-(4-chlorophenyl)propyl]-{2-[3-(3,4,5-trimethoxyphenyl)ureido]cyclopentyl}carbamic acid tert-butyl ester wa...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides compounds of Formula (I): wherein R1-R4 have any of the values defined in the specification that are CCR-3 receptor antagonists, pharmaceutical compositions containing them, methods for their use, and methods and intermediates useful for preparing them.

Description

CROSS-REFERENCE [0001] This application is a division of copending U.S. Ser. No. 10 / 242,610, filed Sep. 12, 2002, which claims the benefit of U.S. Provisional Patent Application Ser. No. 60 / 318,992, filed Sep. 13, 2001, both incorporated herein by reference in their entirety.FIELD OF THE INVENTION [0002] The invention relates to certain 1,2-diaminocyclopentane derivatives that are CCR-3 receptor antagonists, pharmaceutical compositions containing them, methods for their use, and methods and intermediates useful for preparing them. BACKGROUND OF THE INVENTION [0003] Tissue eosinophilia is a feature of a number of pathological conditions such as asthma, rhinitis, eczema and parasitic infections ((see Bousquet, J. et al., N. Eng. J. Med. 323: 1033-1039 (1990) and Kay, A. B. and Corrigan, C. J., Br. Med. Bull. 48:51-64 (1992)). In asthma, eosinophil accumulation and activation are associated with damage to bronchial epithelium and hyperresponsiveness to constrictor mediators. Chemokines...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K31/17A61K31/166C07C275/32A61K31/505A61P11/06A61P43/00C07C275/34C07C317/44C07D239/38
CPCC07C275/34C07C317/44C07C2101/08C07D239/38C07C2601/08A61P11/06A61P43/00C07C233/41
InventorDU BOIS, DAISY JOE
OwnerDU BOIS DAISY JOE