Claims
- 1. A compound of the formula (I): or a pharmaceutically acceptable salt thereof, wherein R1 is selected from1) hydrogen atom, or 2) a C1-6 alkyl group which may be optionally substituted with carboxyl group or a C1-6 alkoxycarbonyl group; R2a and R2b are independently hydrogen atom, hydroxyl group, cyano group, a C1-6 alkythio group which may be optionally substituted with 1 to 3 halogen atoms, a C1-6 alkylsulfinyl group which may be optionally substituted with 1 to 3 halogen atoms, a C1-6 alkylsulfonyl group which may be optionally substituted with 1 to 3 halogen atoms, or a C1-6 alkoxy group which may be optionally substituted with 1 to 3 halogen atoms; R3 is a C1-6 alkyl group; and R4 and R5 are independently a halogen atom.
- 2. The compound according to claim 1, wherein R1 is hydrogen atom or a C1-6 alkyl group which may be optionally substituted with carboxyl group or a C1-6 alkoxycarbonyl group, R2a and R2b are independently hydrogen atom, hydroxyl group, cyano group or a C1-6 alkoxy group which may be optionally substituted with 1-3 halogen atoms, R3 is a C1-6 alkyl group, and R4 and R5 are independently a halogen atom.
- 3. The compound according to claim 2, wherein R1 is hydrogen atom or a C1-6 alkyl group, one of R2a and R2b is hydrogen atom, and the other is a cyano group, or a C1-6 alkoxy group which may be optionally substituted with 1-3 halogen atoms, R3 is a C1-6 alkyl group, and R4 and R5 are independently a halogen atom.
- 4. The compound according to claim 3, wherein R1 is hydrogen atom or methyl group, one of R2a and R2b is hydrogen atom and the other is cyano group, a C1-6 alkoxy group or trifluoromethoxy group, R3 is methyl group, R4 and R5 are chlorine atom.
- 5. The compound according to claim 2, wherein R1 is a C1-6 alkyl group which is substituted with a C1-6 alkoxycarbonyl group or carboxyl group, one of R2a and R2b is hydrogen atom, and the other is a cyano group, or C1-6 alkoxy group which may be optionally substituted with 1-3 halogen atoms, R3 is a C1-6 alkyl group, and R4 and R5 are independently a halogen atom.
- 6. The compound according to claim 5, R3 is methyl group, and R4 and R5 are chlorine atom.
- 7. The compound according to claim 1, wherein the compound is selected from:3-(2,6-Dichloro-4-pyrydyl)-5-(4-propoxybenzyl)-1,5-dimethyl-2,4-imidazolidinedione, 3-(2,6-Dichloro-4-pyrydyl)-5-(4-ethoxybenzyl)-1,5-dimethyl-2,4-imidazolidinedione, 3-(2,6-dichloro-4-pyrydyl)-5-(4-(1,1,1trifluoromethoxybenzyl)]-5-methyl-2,4-imidazolidinedione, 3-(2,6-dichloro-4-pyrydyl)-5-[4-(1,1,1trifluoromethoxybenzyl)]-1,5-Dimethyl-2,4-imidazolidinedione, 3-(2,6-Dichloro-4-pyrydyl)-5-(4-Cyanobenzyl)-5-methyl-2,4-imidazolidinedione, 3-(2,6-Dichloro-4-pyrydyl)-5-(4-Cyanobenzyl)-1,5-dimethyl-2,4-imidazolidinedione; and a pharmaceutically acceptable salt of these compounds.
- 8. A process for preparing a compound of the formula (I-a): or a pharmaceutically acceptable salt thereof, wherein R2a and R2b are independently hydrogen atom, hydroxyl group, cyano group, a C1-6 alkylthio group which may be optionally substituted with 1 to 3 halogen atoms, a C1-6 alkylsulfinyl group which may be optionally substituted with 1 to 3 halogen atoms, a C1-6 alkylsulfonyl group which may be optionally substituted with 1 to 3 halogen atoms, or a C1-6 alkoxy group which may be optionally substituted with 1 to 3 halogen atoms;R3 is a C1-6 alkyl group; R4 and R5 are independently a halogen atom; which comprises cyclizing the compound of the formula (II): wherein OR6 is a hydroxyl group or a protected hydroxyl group, and the other symbols are the same as defined above, and converting into the pharmaceutically acceptable salt, if necessary.
- 9. A process for preparing a compound of the formula (I-b): or a pharmaceutically acceptable salt thereof, whereinR11 is a C1-6 alkyl group which may be optionally substituted with carboxyl group or a C1-6 alkoxycarbonyl group; R2a and R2b are independently hydrogen atom, hydroxyl group, cyano group, a C1-6 alkylthio group which may be optionally substituted with 1 to 3 halogen atoms, a C1-6 alkylsulfinyl group which may be optionally substituted with 1 to 3 halogen atoms, a C1-6 alkylsulfonyl group which may be optionally substituted with 1 to 3 halogen atoms, or a C1-6 alkoxy group which may be optionally substituted with 1 to 3 halogen atoms; R3 is a C1-6 alkyl group; R4 and R5 are independently a halogen atom; which comprises (1) alkylating a compound of the formula (I-a): wherein the symbols are the same as defined above,(2) hydrolyzing the resulting compound, if necessary, and (3) converting into the pharmaceutically acceptable salt, if further desired.
- 10. A process for preparing a compound of the formula (I-c): or a pharmaceutically acceptable salt thereof, whereinR11 is a C1-6 alkyl group which may be optionally substituted with carboxyl group or a C1-6 alkoxycarbonyl group; R21 is a C1-6 alkoxy group which may be optionally substituted with 1 to 3 halogen atoms; R3 is a C1-6 alkyl group; R4 and R5 are independently a halogen atom; which comprises alkylating a compound of the formula (I-d): wherein R1 is hydrogen atom or a C1-6 alkyl group which may be optionally substituted with carboxyl group or a C1-6 alkoxycarbonyl group, and the other symbols are the same as defined above, and converting into the pharmaceutically acceptable salt, if necessary.
- 11. A pharmaceutical composition which comprises a therapeutically effective amount of the compound as set forth in any one of claims 1-7 in admixture with a therapeutically acceptable carrier or diluent.
- 12. A method for treatment or prevention of αLβ2 adhesion mediated condition in a mammal comprising administering a therapeutically effective amount of the compound as set forth in any one of claims 1-7.
- 13. The method according to claim 12, said condition is selected from rheumatoid arthritis, asthma, allergy conditions, adult respiratory distress syndrome, AIDS, cardiovascular diseases, thrombosis, harmful platelet aggregation, reocclusion following thrombolysis, reperfusion injury, skin inflammatory diseases, osteoporosis, osteoarthritis, arteriosclerosis, neoplastic diseases, wound, detaching retina, Type I diabetes, multiple sclerosis, systemic lupus erythematosus, ophthalmic inflammatory conditions, inflammatory bowel diseases, regional enteritis, Sjogren's Syndrome, and rejection after transplantation.
- 14. The method according to claim 13, wherein said diseases is selected from psoriasis, rheumatoid arthritis, inflammatory bowel diseases (Crohn's disease, ulcerative colitis), systemic lupus erythematosus, atopic dermatitis, Sjogren's Syndrome, rejection after transplantation (allograft rejection and graft vs. host disease).
Parent Case Info
This application is the national phase under 35 U.S.C. §371 of PCT International Application No. PCT/US01/12323 now WO 01/92253, which has an International filing date of Apr. 17, 2001, which designated the United States of America. This application claims priority on provisional Application No. 60/207,968 filed on May 31, 2000, the entire contents of which are hereby incorporated by reference.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/US01/12323 |
|
WO |
00 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO01/92253 |
12/6/2001 |
WO |
A |
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4944791 |
Schroder et al. |
Jul 1990 |
A |
6350763 |
Kelly et al. |
Feb 2002 |
B1 |
Foreign Referenced Citations (2)
Number |
Date |
Country |
0 770 613 |
May 1997 |
EP |
WO 01 07048 |
Feb 2001 |
WO |
Non-Patent Literature Citations (1)
Entry |
Kelly, Terence A. et al., J. Immunol. , vol. 163(10), pp. 5173-5177, 1999. |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/207968 |
May 2000 |
US |