1. An address inquiry system for informing an inquirer of a new address of a changer based on an old address of the changer via an Internet, the old address having been changed to the new address, the system comprising:
a data base relationally storing at least the old address, the new address, and an address disclosing condition capable of setting a condition whereby the changer judges whether to give permission to disclose the new address;
a means for searching the new address corresponding to the old address and the address disclosing condition from the data base when the inquirer sends an inquiry including the old address;
a means for making the changer confirm whether the new address is disclosed when the address disclosing condition in searching includes the set condition; and
a means for informing the inquirer of the new address via the system when the changer permits the disclosure of the new address.
2. The address inquiry system as set forth in claim 1,
wherein the data base includes a list of specific inquirers who are refused inquiries about the new address,
the system further comprising:
a means for refusing an inquiry from the inquirer included in the list.
3. The address inquiry system as set forth in claim 1,
wherein the data base relationally stores a plurality of old addresses and one new address.
4. The address inquiry system as set forth in claim 3,
wherein the address disclosing condition is allowed to be set on each of the plurality of old addresses in the data base.
5. The address inquiry system as set forth in claim 1,
wherein the old address and the new address each include at least one sort out of an electronic mail address, an IP address, a Uniform Resource Locator, a telephone number, an address, and a residence.
6. The address inquiry system as set forth in claim 5, further comprising:
a means for informing the inquirer of the new address of a predetermined sort according to the sort of the old address included in the inquiry sent from the inquirer.
7. The address inquiry system as set forth in claim 1,
wherein the inquiry sent from the inquirer includes a message text sent from the inquirer to the changer,
the system further comprising:
a means for sending the message text to make the changer confirm whether the new address is disclosed according to the selection of the changer.
8. A system for making an inquiry about an address, comprising:
an address data base, in which a registrant registers his or her own address, relationally storing an address disclosing condition for an inquirer who wishes to know the address of the registrant;
a disclosure judging means for judging whether to disclose the address to the inquirer based on the address disclosing condition when the inquirer makes an inquiry about the address of the registrant; and
an address disclosing means for disclosing the address of the registrant to the inquirer via the system if the disclosure judging means judges that the address is disclosed,
wherein the disclosing condition includes information about inquirers to whom the address is disclosed or not disclosed,
wherein the disclosure judging means includes a confirming means for making the registrant confirm whether the address is disclosed to the inquirer when the inquirer who inquires about the address is not registered in the inquirers in the disclosing condition,
wherein the confirming means informs the registrant of the attribute information about the inquirer at the time of confirmation,
wherein the address data base stores one, or two or more old addresses of the registrant, and
wherein the disclosure judging means receives the old address of the registrant in the inquiry about the address of the registrant from the inquirer and acquires the address disclosing condition of the registrant by searching the address data base with this old address.
9. The system as set forth in claim 8,
wherein the address data base stores one, or two or more old addresses of the registrant, and
wherein the disclosure judging means receives the old address of the registrant in the inquiry about the address of the registrant from the inquirer and acquires the address disclosing condition of the registrant by searching the address data base with this old address.
10. The system as set forth in claim 8,
wherein the information about the inquirers to whom the address is disclosed or not disclosed includes information that the address is disclosed or not disclosed to all of the inquirers or only a part thereof.
11. The system as set forth in claim 8,
wherein the attribute information includes a profile of the inquirer.
12. The system as set forth in claim 8, further comprising:
an inquirer attribute information storing means for previously storing the attribute information about the inquirer; and
an inquirer attribute information registering means for accepting registration of the attribute information from the inquirer when the attribute information of the inquirer is not stored by the inquirer attribute information storing means.
13. The system as set forth in claim 8,
wherein the confirming means allows a part or all of a message to the registrant received from the inquirer to be sent to the registrant.
14. The system as set forth in claim 8,
wherein the confirming means includes a disclosing condition registering means for receiving a confirmation result from the registrant and registering the inquirer in the disclosing condition as an inquirer to whom the address is disclosed or not disclosed.
15. The system as set forth in claim 8,
wherein the disclosure judging means refuses to disclose the address to the inquirer when a response to a confirmation requested by the confirming means is not obtained from the registrant before a predetermined deadline.
16. The system as set forth in claim 8, further comprising:
a means for informing the registrant that the inquirer made the inquiry about the address.
17. The system as set forth in claim 8,
wherein the address is an electronic mail address.
18. The system as set forth in claim 8,
wherein the address is a home page address.
19. The system as set forth in claim 8,
wherein the address is a telephone number or an addressresidence.
20. A computer software product for instructing a computer system to inquire of a system according to claim 8 for making an inquiry about an address comprising:
a storage medium; and
an inquiry instructing means, stored in the storage medium and started based on the return of an electronic mail because its destination is unknown, for instructing the computer system to inquire of the system for making the inquiry about the address about an electronic mail address of an addressee of the electronic mail.
21. A computer software product for instructing a computer system to inquire of a system according to claim 8 for making an inquiry about an address, comprising:
a storage medium; and
an inquiry instructing means, stored in the storage medium and started based on the impossibility of display of a home page because its destination is unknown, for instructing the computer system to inquire of the system for making the inquiry, about the address about an address of the home page.
22. The computer software product as set forth in claim 21, further comprising:
a home page displaying means for instructing the computer system to display the home page concerned in the address based on the disclosure of the address by the system for inquiring about the address.
23. A method for inquiring about an address of a registrant with a system connecting to an Internet, comprising:
an inquiry receiving step of receiving an inquiry about the address of the registrant from an inquirer;
a registration judging step of judging whether the registrant is registered in an address data base;
a disclosure judging step of judging whether the address is disclosed to the inquirer based on a predetermined disclosing condition when the registrant is registered in the address data base; and
an address disclosing step of disclosing the address of the registrant to the inquirer via the system if it is judged that the address is disclosed in the disclosure judging step,
wherein the disclosing condition includes information about inquirers to whom the address is disclosed or not disclosed,
wherein the disclosure judging step includes a confirming step of making the registrant confirm whether the address is disclosed to the inquirer when the inquirer who inquires about the address is not registered in the inquirers in the disclosing condition wherein attribute information about the inquirer is reported to the registrant in the confirming step, and
wherein it is judged whether the registrant is registered by searching the data base with an old address of the registrant in the registration judging step.
24. The method as set forth in claim 23,
wherein the registration judging step includes a step of making the inquirer select a registrant whose address the inquirer inquires about when the old address of the registrant is registered for a plurality of registrants in the data base.
25. The method as set forth in claim 23,
wherein the attribute information includes a profile of the inquirer.
26. The method as set forth in claim 23, further comprising:
an inquirer attribute information storing step of previously receiving and storing the attribute information about the inquirer.
27. The method as set forth in claim 23,
wherein a part or all of a message to the registrant received from the inquirer is allowed to be sent to the registrant in the confirming step.
28. The method as set forth in claim 23,
wherein the confirming step includes a disclosing condition registering step of receiving a confirmation result from the registrant and registering the inquirer in the disclosing condition as an inquirer to whom the address is disclosed or not disclosed.
29. The method as set forth in claim 23,
wherein the disclosure of the address to the inquirer is refused in the disclosure judging step when a response to a confirmation requested in the confirming step is not obtained from the registrant before a predetermined deadline.
30. The method as set forth in claim 23, further comprising:
a step of informing the registrant that the inquirer made the inquiry about the address.
31. The method as set forth in claim 23,
wherein the address is an electronic mail address.
32. The method as set forth in claim 23,
wherein the address is a home page address.
33. The method as set forth in claim 23,
wherein the address is a telephone number or an addressresidence.
34. The method as set forth in claim 31, further comprising:
a step of making an inquiry about the address based on the return of an electronic mail sent from the inquirer to the registrant because its destination is unknown.
35. The method as set forth in claim 32, further comprising:
a step of making an inquiry about the home page address of the registrant based on the refusal of a request for the display of a home page transmitted from the inquirer to the registrant because its destination is unknown.
36. The address inquiry system as set forth in claim 1, wherein the attribute information about the inquirer includes identity information of the inquirer.
37. The address inquiry system as set forth in claim 8, wherein the attribute information about the inquirer includes identity information of the inquirer.
38. The address inquiry system as set forth in claim 23, wherein the attribute information about the inquirer includes identity information of the inquirer.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. A method for treating a subject with an allergic condition, said method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a compound of formula (I):
68
wherein:
Ar2 is a monocyclic or bicyclic ring system, unsaturated, saturated or aromatic, optionally fused, optionally including between 1 and 5 heteroatom ring moieties independently selected from O, S, N, SO2, and CO; said Ar2 ring system being optionally substituted with between 1 and 4 substituents;
R5 and R6 are independently selected from hydrogen and C1-5alkyl;
R7 and R8 are independently hydrogen, C1-5alkyl, C2-5alkenyl, C1-5alkoxy, C1-5alkylthio, halogen, or a 4-7 membered carbocyclyl or heterocyclyl;
alternatively, R7 and R8 can be taken together to form an optionally substituted 5- to 7-membered carbocyclic or heterocyclic ring, which ring may be unsaturated or aromatic, and may be optionally substituted with between one and three substituents independently selected from halo, cyano, amino, hydroxy, nitro, R4, R4O, R4S, R4O(C1-5alkylene)-, R4O(CO), R4(CO), R4(CS), R4(CO)O, R4O(CO)(CO), R4SO2, NHR44(CNH), NHR44SO2, and NHR44(CO);
R4 is H, C1-5alkyl, C2-5alkenyl, C1-5heterocyclyl, (C1-5heterocyclyl)C1-6alkylene, phenyl, benzyl, phenethyl, NH2, mono- or di(C1-6alkyl)N-, (C1-6alkoxy)carbonyl- or R42OR43, wherein R42 is H, C1-5alkyl, C2-5alkenyl, phenyl, benzyl, phenethyl, C1-5heterocyclyl, or (C1-5heterocyclyl)C1-6alkylene and R43 is C1-5alkylene, phenylene, or divalent C1-5heterocyclyl;
R44 can be H in addition to the values for R4;
n is 0, 1, or 2;
G is C3-6alkenediyl or C3-6alkanediyl, optionally substituted with hydroxy, halogen, C1-5alkoxy, C1-5alkyl, oxo, hydroximino, CO2Rk, RkRIN, RkRINCO2, (L)-C1-4alkylene-, (L)-C1-5alkoxy, N3, or (L)-C1-5alkyleneamino;
each of Rk and RI is independently hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl, phenethyl, or C1-5heterocyclyl; alternatively Rk and RI, can be taken together to form an optionally substituted 4- to 7- membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
L is amino, mono- or di-C1-5alkylamino, pyrrolidinyl, morpholinyl, piperidinyl homopiperidinyl, or piperazinyl, wherein available ring nitrogens may be optionally substituted with C1-5alkyl, benzyl, C2-5acyl, C1-5-alkylsulfonyl, or C1-5alkoxycarbonyl;
Ar represents a monocyclic or bicyclic aryl or heteroaryl ring, optionally substituted with between 1 and 3 substituents independently selected from halogen, C1-5alkoxy, C1-5alkyl, C2-5alkenyl, cyano, azido, nitro, R22R23N, R24SO2, R24S, R24SO, R24OCO, R22R23NCO, C1-5haloalkyl, C1-5haloalkoxy, C1-5haloalkylthio, and C1-5alkylthio;
R22 is hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, phenethyl, benzyl, or C1-5heterocyclyl, C2-8acyl, aroyl, R38OCO, R25R26NCO, R38SO, R38SO2, R38S, or R25R26NSO2;
R23 is hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl or C1-5heterocyclyl;
alternatively, R22 and R23 can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
each of R24 and R24 is C1-5alkyl, C3-5alkenyl, phenyl, benzyl, or C1-5heterocyclyl;
R25 and R26 independently are hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl, or C1-5heterocyclyl;
or, alternatively, R25 and R26 can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
W represents O, S, NR27, CO, (CO)NH, NH(CO), CHR28, or a covalent bond;
RZ is H or OH and the dashed line is absent; or RZ is absent where the dashed line is an sp2 bond;
R27 is hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, naphthyl, benzyl, phenethyl,
C1-5heterocyclyl, C2-8acyl, aroyl, R29OCO, R30R31NCO, R29SO, R29S, R29SO2, or R30R31NSO2;
or, alternatively, R27 and part of Ar2 can be taken together to form an optionally substituted 5- or 6-membered heterocyclic ring with optionally 1 to 3 additional heteroatom moieties in the ring selected from O, NR9, NR10, N, SO2, CO, and S; which ring may be saturated, unsaturated or aromatic; R9 and R10 are independently selected from H, C1-3alkyl, and CH2CO2(C1-4alkyl);
R28 is hydrogen, C1-5alkyl, C3-5alkenyl, hydroxy, phenyl, benzyl, C1-5heterocyclyl, R29O R30R31NCO, R29S, R29SO, R29SO, or R30R31NSO2;
R29 is C1-5alkyl, C3-5alkenyl, phenyl, benzyl, or C1-5heterocyclyl;
R30 and R31 are independently selected from hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl, phenethyl, naphthyl, and C1-5heteroaryl;
alternatively, R30 and R31 can be taken together to form an optionally substituted 4- to 7-membered ring carbocyclic or heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
wherein each of the above hydrocarbyl or heterocarbyl groups, unless otherwise indicated, and in addition to any specified substituents, is optionally and independently substituted with between 1 and 3 substituents selected from methyl, halomethyl, hydroxymethyl, halo, hydroxy, amino, nitro, cyano, C1-5alkyl, C1-5alkoxy, COOH, C2-6acyl,
di(C1-4alkyl)aminoC2-5alkylene, di(C1-4alkyl)aminoC2-5alkyl-NHCO, and C1-5haloalkoxy;
or a pharmaceutically acceptable salt, amide, or ester thereof; or a stereoisomeric form thereof.
2. A method of claim 1, wherein Ar2 is selected from 2,5-di(C1-6alkyl)aminopyrrolyl and the following 6 formulae:
69
wherein
each dashed line may be an sp2 bond or absent;
Xc is O, S, or N; and Xd is O or S;
R1 is hydrogen, halogen, C1-5alkoxy, hydroxy, C1-5alkyl, C2-5alkenyl, cyano, nitro, RaRbN, C2-8acyl, C1-5heterocyclyl, (C1-5heterocyclyl)C1-5alkylene, R11S, R11SO, R11SO2, RcOCO, RcRdNCO, or RcRdNSO2; or R1 can be taken together with R27 as provided below;
R2 is hydrogen, halogen, C1-5alkoxy, hydroxy, C1-5alkyl, C2-5alkenyl, cyano, nitro, ReRfN, C1-5heterocyclyl, or C2-8acyl;
R3 is hydrogen, halogen, C1-5alkoxy, hydroxy, C1-5alkyl, C2-5alkenyl, cyano, nitro, RgRhN, C2-8acyl, C1-5heterocyclyl, RhOCO, RgRhNCO, or RgRhNSO2;
Ra is selected from hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl, phenethyl, C1-5heterocyclyl, C2-8acyl, aroyl, RjOCO, RiRjNCO, R12SO, R12SO2, R12S, and RiRjNSO2;
Re is selected from hydrogen, C1-8alkyl, C3-5alkenyl, phenyl, benzyl, phenethyl, C1-5heterocyclyl, C2-8acyl, aroyl, R32OCO, R32R33NCO, R13SO, R13SO2, R13S, and R32R33NSO2;
Rm is selected from hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl, phenethyl, C1-5heterocyclyl, C2-8acyl, aroyl, R34OCO, R34R35NCO, R15SO, R15SO2, R15S, and R34R35NSO2;
Ro is selected from hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl, phenethyl, C1-5heterocyclyl, C2-8acyl, aroyl, R36OCO, R36R37NCO, R19SO, R19SO2, R19S, and R36R37NSO2;
each of Rb, Rf, Rn, Rp, R32, R33, R34, R35, R36, R37, R39, and R40 is independently selected from hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl, phenethyl, and C1-5heteroaryl;
alternatively, Ra and Rb, Re and Rf, Rm and Rn, and Ro and Rp , independently, can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
each of R11, R12, R13, R14, R15, R16, R19, R38, and R41 is independently C1-5alkyl, C3-5alkenyl, phenyl, benzyl, phenethyl, or C1-5heterocyclyl;
each of Rc and Rd, and Ri and Rj are independently are hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl, phenethyl, or C1-5heteroaryl;
alternatively, Rc and Rd, and Ri and Rj, independently, can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
Rg is hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl, phenethyl, or C1-5heterocyclyl, C2-8acyl, aroyl, R17OCO, R17R18NCO, R16S, R16SO, R16SO2, or R17R18NSO2;
Rh is hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl, phenethyl or C1-5heterocyclyl;
alternatively, Rg and Rh can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
R17 and R18 independently are hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, benzyl, or C1-5heterocyclyl;
alternatively, R17 and R18 can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
Ye is nitrogen or R20C;
Ze is nitrogen or R21C;
R20 is hydrogen, halogen, C1-5alkoxy, C1-5alkyl, C2-5alkenyl, cyano, nitro, RmRnN, C2-8acyl, RmOCO, R14S, R14SO, or R14SO2;
R21 is hydrogen, halogen, C1-5alkoxy, C1-5alkyl, C2-5alkenyl, cyano, nitro, R0RpN, C2-8acyl, R16OCO, R11S, R11SO, or R11SO2;
alternatively, R3 and R20 or R3 and R21 can be taken together to form an optionally substituted 5- or 6-membered carbocyclic or heterocyclic ring, which ring may be saturated, unsaturated or aromatic; wherein said ring may be optionally substituted with halo, di(C1-5alkyl)amino, C2-5acyl, and C1-5alkoxy;
R27 is hydrogen, C1-5alkyl, C3-5alkenyl, phenyl, naphthyl, benzyl, phenethyl, C1-5heterocyclyl, C2-8acyl, aroyl, R29OCO, R30R31NCO, R29SO, R29S, R29SO2, or R30R31NSO2;
or, alternatively, R27 and R1 can be taken together to form an optionally substituted 5- or 6-membered heterocyclic ring with optionally 1 to 3 additional heteroatom moieties in the ring selected from O, NR9, NR10, N, SO2, CO, and S; which ring may be saturated, unsaturated or aromatic;
R9and R10 are independently selected from H, C1-3alkyl, and CH2CO2(C1-4alkyl);
Xf is CHR1f, N, NH, CO, SO2, CHSR1f wherein, in formula (f), R1f is hydrogen, halogen, C1-5alkoxy, hydroxy, C1-5alkyl, C3-5alkenyl, cyano, nitro, R39R40N, C2-8acyl, C1-5heterocyclyl, (C1-5heterocyclyl)C1-5alkylene, R41S, R41SO, R41SO2, R39OCO, R39R40NCO, R39R40NSO2, R41SO3 or R39(CO)O;
Yf is CH2, CHR2f, CR2f, O, or NR2f, wherein R2f is H, C1-7alkyl, C3-5alkenyl, C2-8acyl, C1-5heterocyclyl, (C1-5heterocyclyl)-C1-5alkylene, phenyl, (phenyl)-C1-5alkylene, (C3-7cycloalkyl)-C1-5alkylene, (H2NCO)- C1-5alkylene, C1-5haloalkyl, C1-5cyanoalkyl, (C1-5alkoxycarbonyl)C1-5alkylene, and (phenylcarbonyl)NH;
m is 0 or 1;
p is 0 or 1;
wherein each of the above hydrocarbyl or heterocarbyl groups, unless otherwise indicated, and in addition to any specified substituents, is optionally and independently substituted with between 1 and 3 substituents selected from methyl, halomethyl, hydroxymethyl, halo, hydroxy, amino, nitro, cyano, C1-5alkyl, C1-5alkoxy, COOH, C2-6acyl, di(C1-4alkyl)aminoC2-5alkylene, di(C1-4alkyl)amino C2-5alkyl-NHCO, and C1-5haloalkoxy.
3. A method of claim 2, wherein Ar2 is selected from formulae (f).
4. A method of claim 2, wherein Ar2 is formula (e) and R1halogen, C1-5alkoxy, hydroxy, C1-5alkyl, cyano, nitro, and RaRbN, or R1 can be taken together with R27 as provided below;
R2 is hydrogen, halogen, C1-5alkoxy, C1-5alkyl, or ReRfN;
R3 is hydrogen, halogen, C1-5alkoxy, hydroxy, C1-5alkyl, cyano, RgRhN;
R5 and R6 are independently selected from hydrogen and C1-3alkyl;
R7 and R8 independently are taken together to form an optionally substituted 5- to 7-membered carbocyclic or heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
each of Ra, Re, Rm, and Ro is independently selected from hydrogen, C1-5alkyl, C2-8acyl, and the respective ROCO, RRNCO, RS, RSO, RSO2, and RRNSO2 groups;
each of Rb, Rf, Rn, and Rp, is independently selected from hydrogen and C1-5alkyl;
each of R11, R12, R13, R14, R15, R16, R19, and R38 is independently C1-5alkyl;
each of Rc, and Rd, Ri and Rj, Rk and Rl, R32 and R33, R34 and R35, R36 and R37 are independently are hydrogen or C1-5alkyl, or are taken together to form an optionally substituted 4- to 7-membered heterocyclic ring;
Rg is hydrogen, C1-5alkyl, C2-8acyl, R17OCO, R17R18NCO, R16S, R16SO, R16SO2, or R17R18NSO2;
Rh is hydrogen or C1-5alkyl;
alternatively, Rg and Rh can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring;
R17 and R18 independently are hydrogen or C1-5alkyl;
n is 0 or 1;
G is C3-4alkenediyl or C3-4alkanediyl, optionally substituted with hydroxy, halogen, C1-5alkyloxy, (L)-C1-5alkoxy, N3, or (L)-C1-5alkyleneamino;
L is amino, mono- or di-C1-5alkylamino, pyrrolidinyl, morpholinyl, piperidinyl homopiperidinyl, or piperazinyl, wherein available ring nitrogens may be optionally substituted with C1-5alkyl, benzyl, C1-5alkylcarbonyl, or C1-5alkyloxycarbonyl;
Ye is nitrogen or R20C;
Ze is nitrogen or R21C;
R20 and R21 are independently selected from hydrogen, halogen, C1-5alkoxy, C1-5alkyl, cyano, nitro, and RmRnN or RoRpN, respectively;
alternatively, R3 and R20 or R3 and R21 can be taken together to form an optionally substituted 5- or 6-membered carbocyclic or heterocyclic ring;
Ar represents a monocyclic or bicyclic aryl or heteroaryl ring, optionally substituted with between 1 and 3 substituents independently selected from halogen, C1-5alkoxy, C1-5alkyl, cyano, azido, nitro, R22R23N, R24SO2, R24OCO, R25R26NCO, CF3, OCF3, CF3S, and C1-5alkylthio;
R22 is hydrogen, C1-5alkyl, phenyl, benzyl, phenethyl, C1-5heterocyclyl, C2-8acyl, aroyl, R24OCO, R25R26NCO, R24SO, R24SO2, or R25R26NSO2;
R23 is hydrogen or C1-5alkyl;
alternatively, R22 and R23 can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring;
R24 is hydrogen or C1-5alkyl;
R25 and R26 are independently hydrogen or C1-5alkyl;
or, alternatively, R25 and R26 can be taken together to form an optionally substituted 4- to 7-membered heterocyclic;
W is NR27 or CHR28;
R27 is hydrogen, C1-5alkyl, R29OCO, R30R31NCO, R29SO, R29SO2, or R30R31NSO2;
or, alternatively, R27 and R1 can be taken together to form an optionally substituted 5- or 6-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
R28 is hydrogen, hydroxy, C1-5heterocyclyl, phenyl, or C1-5alkyl;
R29 is C1-5alkyl; and
R30 and R31 are independently selected from hydrogen, C1-5alkyl; alternatively, R30 and R31 can be taken together to form an optionally substituted 4- to 7-membered heterocyclic.
5. A method of claim 1, wherein
one of R5 and R6 is H,
R7 and R8 are taken together to form an optionally substituted 6-membered carbocyclic or heterocyclic ring; and
Ar represents a monocyclic ring, optionally substituted with 1 to 2 substituents selected from halogen, C1-5alkyl, cyano, azido, nitro, R22R23N, CF3 and OCF3.
6. A method of claim 5, wherein both R5 and R6 are each H, and Ar is a six membered ring substituted with between 1 and 2 substituents independently selected from halogen, methyl, CF3, and OCF3, said substituent or substituents being at the 4-position, or at the 3- and 4-positions.
7. A method of claim 2, wherein R20 and R3 taken together are a six-membered carbocyclic or heterocyclic ring optionally substituted with between 1 and 3 substituents independently selected from halo, C1-3alkoxy, di(C1-3alkyl)amino, and C2-5acyl.
8. A method of claim 1, wherein said compound is selected from:
1-(1-2-Hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2-one;
1-(1-3-3-(3,4-Dichloro-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2-one;
3-(3,4-Dichloro-phenyl)-1-3-4-(2-oxo-2 ,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl-propyl-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridine-5-carboxylic acid amide;
6-Chloro-1-(1-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2-one;
3-(3,4-Dichloro-phenyl)-1-3-4-(3-methyl-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl-propyl-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridine-5-carboxylic acid amide;
3-(1-2-Hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-2-oxo-2,3-dihydro-benzoimidazol-1-yl-acetonitrile;
3-(1-2-Hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-2-oxo-2,3-dihydro-benzoimidazol-1-yl-acetic acid ethyl ester;
5-Chloro-3-(1-2-hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4 ,3-cpyridin-1-yl-propyl-piperidin-4-yl)-1-methyl-1,3-dihydro-benzoimidazol-2-one;
1-3-4-(6-Chloro-3-methyl-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl-propyl-3-(3,4-dichloro-phenyl)-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridine-5-carboxylic acid amide;
3-(1-2-Hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-1,5-dimethyl-1,3-dihydro-benzoimidazol-2-one;
3-(1-2-Hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-1,3-dihydro-imidazo4,5-bpyridin-2-one;
3-(1-3-3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-2-hydroxy-propyl-piperidin-4-yl)-5-methoxy-1,3-dihydro-imidazo4,5-bpyridin-2-one;
3-(4-Bromo-phenyl)-1-2-hydroxy-3-4-(5-methoxy-2-oxo-1,2-dihydro-imidazo4,5-bpyridin-3-yl)-piperidin-1-yl-propyl-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridine-5-carboxylic acid amide;
3-(1-2-Hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-5-methoxy-1-methyl-1,3-dihydro-imidazo4,5-bpyridin-2-one;
5-Dimethylamino-3-(1-2-hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-1,3-dihydro-imidazo4,5-bpyridin-2-one;
6-Chloro-1-(1-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-1,3-dihydro-indol-2-one;
1-(1-2-Hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-3,4-dihydro-1H-quinolin-2-one;
4-(1-3-5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-4H-benzo1,4oxazin-3-one;
4-(1-2-Hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-4H-benzo1,4oxazin-3-one; and
1-(1-3-5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-3,4-dihydro-1H-quinazolin-2-one.
9. A method of claim 1, wherein said compound is selected from:
3-(1-2-Hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-2-oxo-2,3-dihydro-benzoimidazol-1-yl-acetonitrile; and 4-(1-2-Hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-4H-benzo1 ,4oxazin-3-one.
10. A method of claim 1, wherein said compound is selected from:
2-(1-3-5-Acetyl-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-2-hydroxy-propyl-piperidin-4-ylamino)-benzonitrile;
1-(1-3-5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-2-hydroxy-propyl-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2-one;
3-(1-3-5-Acetyl-3-(4-bromo-phenyl)-4,5,6 ,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-2-hydroxy-propyl-piperidin-4-yl)-3H-benzooxazol-2-one;
1-(3-(4-Chloro-3-methyl-phenyl)-1-3-4-(3,4-dichloro-phenoxy)-piperidin-1-yl-propyl-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridin-5-yl)-ethanone;
1-(3-(4-Chloro-3-methyl-phenyl)-1-3-4-(2,3-dihydro-indol-1-yl)-piperidin-1-yl-2-hydroxy-propyl-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridin-5-yl)-ethanone;
(S)-1-(1-3-5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-2-hydroxy-propyl-piperidin-4-yl)-6-chloro-1,3-dihydro-benzoimidazol-2-one;
1-(1-3-5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-2-hydroxy-propyl-piperidin-4-yl)-3-(2-morpholin-4-yl-ethyl)-1,3-dihydro-benzoimidazol-2-one;
1-(1-3-3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-2-hydroxy-propyl-piperidin-4-yl)-6-chloro-1,3-dihydro-benzoimidazol-2-one;
3-(1-3-5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-2-oxo-2,3-dihydro-benzoimidazol-1-yl-acetonitrile;
6-Chloro-1-(1-2-hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-3,4-dihydro-1H-quinazolin-2-one;
1-4-(6-Chloro-2,2-dioxo-3,4-dihydro-2H-26-benzo1,2,6thiadiazin-1-yl)-piperidin-1-yl-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propan-2-ol;
4-(1-2-Hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-4H-pyrido3,2-b1,4oxazin-3-one;
5-Chloro-1-(1-2-hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-1,3-dihydro-indol-2-one;
1-4-(6-Chloro-indol-1-yl)-piperidin-1-yl-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propan-2-ol;
1-(1-3-5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-1H-benzotriazole;
1-3-4-(3-Methyl-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl-propyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridine-5-sulfonic acid amide;
5-Chloro-3-(1-2-hydroxy-3-4-pyridin-4-yl-3-(4-trifluoromethyl-phenyl)-pyrazol-1-yl-propyl-piperidin-4-yl)-1-methyl-1,3-dihydro-benzoimidazol-2-one;
4-(1-2-Hydroxy-3-4-pyrazin-2-yl-3-(4-trifluoromethyl-phenyl)-pyrazol-1-yl-propyl-piperidin-4-yl)-4H-benzo1,4oxazin-3-one;
(S)-1-(1-2-Hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-3-methyl-1,3-dihydro-benzoimidazol-2-one; and
(S)-5-Dimethylamino-3-(1-2-hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-1-methyl-1,3-dihydro-imidazo4,5-bpyridin-2-one.
5-Chloro-3-(1-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-1-methyl-1,3-dihydro-benzoimidazol-2-one;
1-(1-3-5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-1,3-dihydro-indol-2-one;
1-3-(4-Chloro-3-methyl-phenyl)-1-(3-4-3-(4-chloro-phenyl)-1,2,4oxadiazol-5-yl-piperidin-1-yl-2-hydroxy-propyl)-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridin-5-yl-ethanone;
1-1-2-Hydroxy-3-4-(5-trifluoromethyl-benzothiazol-2-yl)-piperidin-1-yl-propyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridin-5-yl-ethanone;
1-1-3-4-(Benzodisoxazol-3-yloxy)-piperidin-1-yl-2-hydroxy-propyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridin-5-yl-ethanone;
1-1-3-4-(5-Chloro-benzooxazol-2-yl)-piperidin-1-yl-2-hydroxy-propyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridin-5-yl-ethanone;
1-1-3-4-(Benzothiazol-2-ylamino)-piperidin-1-yl-2-hydroxy-propyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridin-5-yl-ethanone;
1-1-3-4-(3,5-Dichloro-pyridin-4-yloxy)-piperidin-1-yl-2-hydroxy-propyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridin-5-y-ethanone;
-1-3-4-(1H-Benzoimidazol-2-yl)-piperidin-1-yl-2-hydroxy-propyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo4,3-cpyridin-5-yl-ethanone;
6-Chloro-4-(1-2-hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-4H-benzo1,4oxazin-3-one;
6-Chloro-1-(1-2-hydroxy-3-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-propyl-piperidin-4-yl)-3,4-dihydro-1H-quinolin-2-one;
11. A method of claim 1, wherein said compound is selected from:
1-(1-3-5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-2-hydroxy-propyl-piperidin-4-yl)-5-methoxy-1,3-dihydro-benzoimidazol-2-one;
6-Chloro-1-(1-3-3-(4-chloro-3-methyl-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo4,3-cpyridin-1-yl-2-hydroxy-propyl-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2-one;
12. A method of claim 1, wherein said pharmaceutical composition is formulated in a dosage amount appropriate for the treatment of an allergic condition.