ZA200302056B

ZA200302056B - Substituted pyrazoles.

Info

Publication number: ZA200302056B
Application number: ZA200302056A
Authority: ZA
Inventors: Christopher R Butler; James P Edwards; Darin J Gustin; Steven P Meduna; Clark A Sehon; Jianmei Wei; Hui Cai; Cheryl A Grice; Haripada Khatuya; Barbara A Pio; Kevin L Tays
Original assignee: Ortho Mcneil Pharm Inc
Priority date: 2000-08-14
Filing date: 2003-03-13
Publication date: 2004-07-02
Also published as: CN1982308A; ZA200302051B; CN1982308B; AR035713A1

Description

SUBSTITUTED PYRAZOLES

. Field of the Invention

Ko h 5 This invention relates to a series of substituted pyrazoles, pharmaceutical compositions containing these compounds, and intermediates used in their manufacture, and methods of using them.

Backdround of the Invention

Cathepsin S (EC 3.4.22.27) is a cysteine protease of the papain family found primarily in lysosomes (Bromme, D.; McGrath, M. E. High Level

Expression and Crystallization of Recombinant Human Cathepsin S. Protein

Science 1996, 5, 789-791). :

The role of cathepsin S in the immune response is anticipated by its tissue distribution: cathepsin S is found primarily in lymphatic tissues, lymph nodes, the spleen, B lymphocytes, and macrophages (Kirschke, H. Chapter 211. Cathepsin S. In Handbook of Proteolytic Enzymes. Barrett, A. J.;

Rawlings, N. D.; Woessner, J. F,, Eds. San Diego: Academic Press, 1998. pp. 621-624.). Cathepsin S inhibitors have been shown in animal models to modulate antigen presentation and are effective in an animal model of asthma (Riese, R. J.; Mitchell, R. N.; Villadangos, J. A.; Shi, G.-P.; Palmer, J. T.; Karp,

E.R; De Sanctis, G. T.; Ploegh, H. L.; Chapman, H. A. Cathepsin S Activity

Regulates Antigen Presentation and Immunity. J. Clin. Invest. 1998, 101, 2351-2363 and Shi, G.-P.; Villadangos, J. A.; Dranoff, G.; Small, C.; Gu, L.;

Haley, K. J.; Riese, R.; Ploegh, H. L.; Chapman, H. A. Cathepsin S Required . for Normal MHC Class Il Peptide Loading and Germinal Center Development. . Immunity 1999, 10, 197-208.).

Mice in which the gene encoding cathepsin S has been knocked out are less susceptible to collagen-induced arthritis and their immune systems have an impaired ability to respond to antigens (Nakagawa, T. Y.; Brissette, W. H.; ) Lira, P. D.; Griffiths, R. J.; Petrushova, N.; Stock, J.; McNeish, J. D.; Eastman, . 5 S.E.; Howard, E. D.; Clarke, S. R. M.; Rosloniec, E. F.; Elliott, E. A.;

Rudensky, A. Y. Impaired Invariant Chain Degradation and Antigen

Presentation and Diminished Collagen-induced Arthritis in Cathepsin S Null

Mice. Immunity 1999, 10, 207-217).

These data demonstrate that compounds that inhibit the proteolytic activity of human cathepsin S should find utility in the treatment of chronic autoimmune diseases including, but not limited to, lupus, rheumatoid arthritis, and asthma; and have potential utility in modulating the immune response to tissue transplantation.

There are a number of cathepsin S inhibitors reported in the literature.

The most important patents are listed below.

Certain dipeptidyl nitriles are claimed by Novartis as cathepsin S inhibitors in: Altmann, et. al. WO-99/24460.

Dipeptidy! vinyl sulfones are claimed by Arris (now Axys) as cysteine protease (including cathepsin S) inhibitors in: Palmer, et. al. US-5976858.

Certain peptidyl sulfonamides are ciaimed by Arris/Axys as cysteine protease (including cathepsin S) inhibitors in: Palmer, et. al. US-5776718 (assigned to Arris, now Axys) & Klaus, et. al. US-6030946 (assigned to Axys). : p Compounds somewhat similar to those of the present invention are o 30 described in the following references. lo

Winters, et. al. (Winters, G.; Sala, A.; Barone, D.; Baldoli, E. J. Med,

Chem. 1985, 28, 934-940; Singh, P.; Sharma, R. C. Quant. Struct.-Act. Relat. 2

ENSEISESNsT

1990, 9, 29-32; Winters, G.; Sala, A.; Barone, D. in US-4500525 (1985)) have described bicyclic pyrazoles of the type shown below. R never contains a heterocyclic ring and no protease inhibitor activity is ascribed to these molecules; they are described as a1-adrenergic receptor modulators. \ 5

R.,

N-N

SAY

N:

Rr!

Shutske, et. al. claim the bicylic pyrazoles below. The pyridine ring is aromatic in their system (Shutske, G. M.; Kapples, K. J.; Tomer, J. D. US- 5264576 (1993)). Although reference is made to R being a linker to a heterocycle, the claims specify only R = hydrogen. The compounds are referred to as serotonin reuptake inhibitors.

R, :

N—N

N

(yO ~~

N

The compound 2-[4-[4-(3-methyl-5-phenyl-1H-pyrazol-1-yl)butyl}-1- piperazinyl]-pyrimidine is known from EP-382637, which describes pyrimidines having anxiolytic properties. This compound and analogs are further described in EP-502786 as cardiovascular and central nervous system agents.

Pharmaceutical formulations with such compounds are disclosed in EP-655248 ¢ for use in the treatment of gastric secreation and as anti-ulcer agents. WO- 9721439 describes medicaments with such compounds for treating obsessive- ~ 25 compulsive disorders, sleep apnea, sexual dysfunctions, emesis and motion sickness.

The compounds 5-methyl-3-phenyl-1-[4-(4-phenyl-1-piperazinyl)butyl]- 1H-indazole and 5-bromo-3-(2-chlorophenyl)-1-[4-(4-phenyl-1- piperazinyl)butyl]-1H-indazole, in particular the hydrochloride salts thereof, are known from W0-9853940 and CA 122:314528, where these and similar compounds are described as kinase inhibitors in the former reference and possessing affinity for benzodiazepine receptors in the latter reference. é

Summary of the Invention

The present invention concerns compounds which can be represented i 5 by formula (1):

RS

I

Ar. 3 —=

Sw | . In of "

R® (1) wherein:

Ar, is a monocyclic or bicyclic ring system, unsaturated, saturated or 10 aromatic, optionally fused, optionally including between 1 and 5 heteroatom ring moieties independently selected from O, 8, N, 80,, and C=0; said Ar, ring system being optionally substituted with between 1 and 4 substituents;

R® and R® are independently selected from hydrogen and C, 5 alkyl; 15 R’ and R® are independently hydrogen, C, ; alkyl, C, alkenyl, C, 5 alkoxy, C5 alkylthio, halogen, or a 4-7 membered carbocyclyl or heterocyclyl; alternatively, R” and R® 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 20 one and three substituents independently selected from haio, cyano, amino, hydroxy, nitro, R*, R*O-, R*S-, R*O(C ,; alkylene)-, R*O(C=0)-,

R*(C=0)-, R{C=8)-, R{C=0)0-, R*0(C=0)(C=0)-, R*S0,,

NHR*(C=NH)-, NHR*SO,-, and NHR*(C=0)—; @ R* is H, C ,5 alkyl, C , 5 alkenyl, C , ; heterocyclyl, (C 5 heterocyclyl)C 25 alkylene, phenyl, benzyl, phenethyl, NH,, mono- or di(C , alkyl)N-, (C ,, : alkoxy)carbonyl- or R*?OR*-, wherein R*? is H, C ,; alkyl, C , alkenyl, phenyl, benzyl, phenethyl, C , ; heterocyclyl, or (C ,; heterocyclyl)C alkylene and R*® is C , 5 alkylene, phenylene, or divalent C , heterocyclyl;

R* can be H in addition to the values for R*; u 5 n is0,1,0r2;

G is C,; alkenediyl or C,,; alkanediyl, optionally substituted with hydroxy, halogen, C, salkoxy, C,salkyl, oxo, hydroximino, CO,R¥, R‘R'N,

RR'NCO,, (L)-C ., alkylene-, (L)-C, alkoxy, N; or [(L)-C alkylene]amino; eachof R*and R' is independently hydrogen, C, alkyl, C , alkenyl, phenyl, benzyl, phenethyl, or C ,; heterocyclyl; alternatively R* and R', 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-C, zs alkylamino, pyrrolidinyl, morpholinyl, piperidinyl homopiperidinyl, or piperazinyl, wherein available ring nitrogens may be optionally substituted with C, 5 alkyl, benzyl, C, ; acyl, C, salkylsulfonyl, or

C,s alkoxycarbonyl;

Ar represents a monocyclic or bicyclic aryl or heteroaryl ring, optionally substituted with between 1 and 3 substituents independently selected from halogen, C, ; alkoxy, C, alkyl, C ,s alkenyl, cyano, azido, nitro, R#ZR*N,

R*S0,, R*S, R*S0, R*0C=0, R®R®*NC=0, C, 5 haloalkyl, C, haloalkoxy,

C,shaloalkylthio, and C, ; alkylthio;

R? is hydrogen, C,salkyl, C ,; alkenyl, phenyl, phenethyl, benzyl, or C , heterocyclyl, C 5 acyl, aroyl, R®*0C=0, R®R*NC=0, R¥S0, R¥S0,, R*S, or R*R®*NSO,;

R? is hydrogen, C,salkyl, C 5 alkenyl, phenyl, benzyl! or C , ; heterocyclyl; alternatively, R* and R* can be taken together to form an optionally v substituted 4- to 7- membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic; ¢ each of R* and R* is C, alkyl, C , alkenyl, phenyl, benzyl, or C , heterocyclyl;

R* and R® independently are hydrogen, C, ; alkyl, C 5 alkenyl, phenyl, benzyl, or C , 5 heterocyclyl; or, alternatively, R® and R® can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be “ 5 saturated, unsaturated or aromatic;

W represents O, S, NR¥, C=0, (C=O)NH, NH(C=0), CHR?, or a covalent bond; : R* is H or OH and the dashed line is absent; or R* is absent where the dashed line is an sp? bond;

R¥ is hydrogen, C, alkyl, C ,5 alkenyl, phenyl, naphthyl, benzyl, phenethyl,

C ,5s heterocyclyl, C ,; acyl, aroyl, R®0C=0, R*¥R*NC=0, R®S0, R®S,

R#*S0,, or R°R*NSO, ; or, alternatively, R¥ and part of Ar, 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, NR®,

NR, N, SO,, C=0, and S; which ring may be saturated, unsaturated or aromatic; R°and R" are independently selected from H, C ,, alkyl, and -CH,CO,(C ,, alkyl);

R# is hydrogen, C, alkyl, C , alkenyl, hydroxy, phenyl, benzyl,

C , 5 heterocyclyl, R®0, R¥R*'NC=0, R®S, R*S0, R*S0,, or

R¥R*NSO,;

R# is C,salkyl, C 45 alkenyl, phenyl, benzyl, or C , 5 heterocyclyl;

R¥®and R* are independently selected from hydrogen, C,salkyl, C , alkenyl, phenyl, benzyl, phenethyl, naphthyl, and C , 5 heteroaryl; alternatively, R* and

R®* 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; v 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, C ,; alkyl, C , 5 alkoxy, -COOH, C ,. acyl,

[di(C 4 alkyl)amino]C , 5 alkylene, [di(C ,_, alkyl)amino] C , alkyl-NH-CO-, and C ,_; haloalkoxy; or a pharmaceutically acceptable salt, amide, or ester thereof; or a ’ stereoisomeric form thereof. “ 5 One embodiment of the invention is a compound of formula(l), wherein

Ar, is selected from 5-7 membered monocyclic rings, and [5,6], [6,6], [6,5], and [5,5] fused bicyclic ring systems, said ring or ring system being carbocyclic or heterocyclic, saturated, unsaturated, or aromatic, optionally substituted with halo, C ,, alkyl, C ,, haloalkyl, C ,_, hydroxyalkyl, nitro, hydroxy, amino, mono- or di-(C ,4 alkyl)amino, C ,, alkoxy, C ,, alkoxycarbonyl, C , acyl, C , acyloxy, C ,; alkylsulfonyl, C , 5 alkoxycarbonylC ,_, alkoxy, cyano, and mono- or di~(C ,; alkyl)carbamoy!.

Another embodiment of the invention is a compound of formula (1), wherein Ar, is selected from 2,5-di(C , 5 alkyl)aminopyrrolyl and the following 6 formulae:

N BN rR s R® N

LT Jd

R3 y R20 R20 Xe

R20 (a) (b) (c) 2

N [ R! ( mn we

XN { K! = NE R20

AT A

R20 R3 (d) (e) () © wherein : each dashed line may be an sp? bond or absent;

X.is 0, S,orN; and X;isO or S;

R' is hydrogen, halogen, C, alkoxy, hydroxy, C,salkyl, C ,, alkenyl, cyano, nitro, R*R°N, C ,; acyl, C , heterocyclyl, (C 5 heterocyclyl)C , 5 alkylene, ’ R"S, R"'S0O, R""S0,, R°OC=0, R°R!NC=0, or R°RNSO,; or R' can be “ 5 taken together with R?” as provided below;

R? is hydrogen, halogen, C, 5 alkoxy, hydroxy, C,salkyl, C ,; alkenyl, cyano, nitro, R°R'N, C , 5 heterocyclyl, or C ,, acyl;

R? is hydrogen, halogen, C, ; alkoxy, hydroxy, C,salkyl, C ,5 alkenyl, cyano, nitro, R°R"N, C ,, acyl, C , 4 heterocyclyl, R"OC=0,.R°R"NC=0, or R°R"NSO,;

R®is selected from hydrogen, C, salkyl, C , 5 alkenyl, phenyl, benzyl, phenethyl,

C 5 heterocyclyl, C ,, acyl, aroyl, ROC=0, RRINC=0, R"*S0, R'?S0O,,

R™S, and RRINSO,;

R® is selected from hydrogen, C,salkyl, C ,; alkenyl, phenyl, benzyl, phenethyl,

C ,s heterocyclyl, C ,, acyl, aroyl, R*?0C=0, R¥*R*NC=0, R"*SO, R'*SO,,

R®S, and R¥*R*NSO,;

R™ is selected from hydrogen, C, alkyl, C 55 alkenyl, phenyl, benzyl, phenethyl,

C 5 heterocyclyl, C ,, acyl, aroyl, R*0OC=0, R*¥*R*NC=0, R"S0, R"*S0O,,

RS, and R*R*NSO,;

RC is selected from hydrogen, C, ;alkyl, C ; 5 alkenyl, phenyl, benzyl, phenethyl,

C ,5 heterocyclyl, C ,; acyl, aroyl, R®*0OC=0, R*R¥*NC=0, R"S0O, R'*S0O,,

RS, and R®¥*R¥NSO,; each of R®, R', R", R®, R¥, R®, R¥* R*, R* , R¥, R¥, and Ris independently selected from hydrogen, C, alkyl, C 5 alkenyl, phenyl, benzyl, phenethyl, and

C 5 heteroaryl; alternatively, R? and R®, R® and Rf, R” and R", and R° and R", independently, can be taken together to form an optionally substituted 4- to 7- membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic; p each of R", R"2, R®, R" R®, RS, R", R*®, and R* is independently C, salkyl,

C , 5 alkenyl, phenyl, benzyl, phenethyl, or C, heterocyclyl; © each of R°and R?, and R' and R’ are independently are hydrogen, C, alkyl,

C 55 alkenyl, phenyl, benzyl, phenethyl, or C, ; heteroaryl; alternatively,

R® and RY, and R'and R, independently, can be taken together to form an optionally substituted 4~ to 7- membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;

RY is hydrogen, C, alkyl, C 5 alkenyl, phenyl, benzyl, phenethyl,

C,s heterocyclyl, C,, acyl, aroyl, R70C=0, R7R*NC=0, RS, R"*SO, . 5 R'S0,, or R""R™NSO,;

R" is hydrogen, C,salkyl, C ,5 alkenyl, phenyl, benzyl, phenethyl or

C, 5s heterocyclyl; alternatively, R° and R" can be taken together to form an optionally substituted 4- to 7- membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;

R' and R" independently are hydrogen, C,salkyl, C , 5 alkenyl, phenyl, benzyl, or C,5 heterocyclyl; alternatively, R' and R' can be taken together to form an optionally substituted 4- to 7- membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;

Y, is nitrogen or R*C;

Z, is nitrogen or R*'C ;

R* is hydrogen, halogen, C, salkoxy, C,s alkyl, C , alkenyl, cyano, nitro,

R™R"N, C ,; acyl, R"OC=0, R*S, R“SO or R*SO,;

R*' is hydrogen, halogen, C, alkoxy, C, alkyl, C , 5 alkenyl, cyano, nitro,

R°RPN, C ,; acyl, ROC=0, R"'S, R"SO or R"'SO,; alternatively, R® and R® or R® and R? 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(C ,_; alkyl)amino, C ,5 acyl, and « C , alkoxy; ¢ R¥ is hydrogen, C, alkyl, C 55 alkenyl, phenyl, naphthyl, benzyl, phenethyl,

C , 5 heterocyclyl, C ,, acyl, aroyl, R®0C=0, R*R¥*NC=0, R¥S0, R*S,

R*S0,, or R°R¥'NSO, ;

or, alternatively, R¥ and R' 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, NR®, NR, N,

S0,, C=0, and S; which ring may be saturated, unsaturated or aromatic; . 5 R°and R™ are independently selected from H, C ,, alkyl, and -CH,CO,(C ,_, alkyl);

X; is CHR", =N-, NH, C=0, SO,, CHSR" wherein, in formula (f), R" is hydrogen, halogen, C, ; alkoxy, hydroxy, C, alkyl, C , alkenyl, cyano, nitro, : 10 R¥R*N, C,, acyl, C 5 heterocyclyl, (C ,; heterocyclyl)C , 5 alkylene, R*'S,

R*SO, R*'SO,, R®*0C=0, R*R*NC=0, R*R*“NS0,, R*'SO,- or R*(C=0)0-;

Y, is CH,, CHR*, =CR?, O, or NR?, wherein R¥ is H, C,, alkyl, C , alkenyl,

C,sacyl, C,sheterocyclyl, (C,;heterocyclyl)-C,_; alkylene, phenyl, (phenyl)-C, s alkylene, (C 5; cycloalkyl)-C, ; alkylene, (H,NCO)- C5 alkylene, C, haloalkyl, C, cyanoalkyl, (C,; alkoxycarbonyl)C, alkylene, and (phenylcarbonyl)NH-; mis Oor 1; pisOor1,; 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, C , alkyl, C , alkoxy, -COOH, C ,, acyi, [di(C , alkyl)amino]C ,; alkyiene, [di(C ,, alkyl)amino] C ,. alkyl-NH-CO-, and C , haloalkoxy.

The disclosed compounds are high-affinity inhibitors of the proteolytic . activity of human cathepsin S. For use in medicine, the preparation of pharmaceutically acceptable salts of compounds of formula (I) may be i desirable.

Certain compounds of the present invention may have one stereogenic atom and may exist as two enantiomers. Certain compounds of the present invention may have two or more stereogenic atoms and may further exist as diastereomers. It is to be understood by those skilled in the art that all such . 5 stereoisomers and mixtures thereof in any proportion are encompassed within the scope of the present invention.

Another aspect of the invention provides pharmaceutical compositions comprising a compound of formula (1) and a pharmaceutically acceptable carrier. A further embodiment of the invention is a process for making a pharmaceutical composition comprising mixing a disclosed compound as described above, with a suitable pharmaceutically acceptable carrier.

The invention also contemplates pharmaceutical compositions comprising more than one compound of formula (I) and compositions comprising a compound of formula (I) and another pharmaceutically active agent.

The invention features a method of treating disorders or conditions mediated by the cathepsin S enzyme, in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of any of the compounds or pharmaceutical compositions described above. If more than one active agent is administered, the therapeutically effective amount may be a jointly effective amount. The compounds described herein inhibit the protease activity of human cathepsin S, an enzyme involved in the immune response. In preferred embodiments, cathepsin S inhibition is selective. As such, the disclosed compounds and compositions are useful in the prevention, inhibition, or treatment of autoimmune diseases such as lupus, rheumatoid arthritis, and » asthma, and for the prevention, inhibition, or treatment of tissue transplant rejection.

Additional features and advantages of the invention will become apparent from the detailed description below, including examples, and the appended claims.

Detailed Description of the Invention

The invention features pyrazole compounds of formula (1), methods of " 5 making them, compositions containing them, and methods of using them to treat diseases and conditions, including those mediated by Cathepsin S.

A. Terms

The following terms are defined below and by their usage throughout this disclosure. “Alkyl” includes optionally substituted straight chain and branched hydrocarbons with at least one hydrogen removed to form a radical group.

Alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, 1- methyipropyl, pentyl, isopentyl, sec-pentyl, hexyl, heptyl, octyl, and so on.

Alkyl includes cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. : “Alkenyl” includes optionally substituted straight chain and branched hydrocarbon radicals as above with at least one carbon-carbon double bond (sp®). Alkenyls include etheny! (or vinyl), prop-1-enyl, prop-2-enyl (or allyl), isopropenyl (or 1-methylvinyl), but-1-enyl, but-2-enyl, butadienyis, pentenyls, hexa-2,4-dienyl, and so on. Hydrocarbon radicals having a mixture of double bonds and triple bonds, such as 2-penten-4-ynyl, are grouped as alkynyls herein. Alkenyl includes cycloalkenyl. Cis and trans or (E) and (Z) forms are included within the invention. - “Alkynyl” includes optionally substituted straight chain and branched hydrocarbon radicals as above with at least one carbon-carbon triple bond (sp). ) Alkynyls include ethynyl, propynyls, butynyls, and pentynyls. Hydrocarbon radicals having a mixture of double bonds and triple bonds, such as 2-penten- 4-ynyl, are grouped as alkynyls herein. Alkynyl does not include cycloalkynyl.

Claims

1. A compound of formula |: . 5 . RS NON Ar Aas Se In r R? Le R (1) wherein: Ar, 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, SO,, and C=0; said Ar, ring system being optionally substituted with between 1 and 4 substituents; R°® and R?® are independently selected from hydrogen and C, alkyl; R” and R® are independently hydrogen, C, ; alkyl, C, alkenyl, C, 5 alkoxy, C,s alkylthio, halogen, or a 4-7 membered carbocyclyl or heterocyclyl; alternatively, R” and R® 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, R*, R*0-, R*S-, R‘O(C ,; alkylene)-, - R*O(C=0)-, R{C=0)-, R{C=S)-, RYC=0)0-, R*O(C=0)(C=0)-, R*SO,, NHR*(C=NH)~, NHR*SO,-, and NHR*(C=0)-; « R* is H, C 5 alkyl, C ,5 alkenyl, C , heterocyclyl, (C ,5 heterocyclyl)C , alkylene, phenyl, benzyl, phenethyl, NH,, mono- or di(C ,, alkyl)N-, (C ‘ alkoxy)carbonyl- or R*?OR*-, wherein R* is H, C , 5 alkyl, C , alkenyl, phenyl, benzyl, phenethyl, C 5; heterocyclyl, or (C ,; heterocyclyl)C

02/2035 alkylene and R* is C ,; alkylene, phenylene, or divalent C , heterocyclyl; R* can be H in addition to the values for R%; eo 5 n is 0,1, or 2; ‘ G is Cy alkenediyl or C;, alkanediyl, optionally substituted with hydroxy, halogen, C, salkoxy, C, alkyl, oxo, hydroximino, CO,R¥, R‘R'N, RR'NCO,, (L)-C ,, alkylene-, (L)-C, salkoxy, N,, or [(L)-C 5 alkylene]amino; each of R“and R' is independently hydrogen, C,; alkyl, C , alkenyl, phenyl, benzyl, phenethyl, or C , ; heterocyclyl; alternatively R*and R', 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-C, ;alkylamino, pyrrolidinyl, morpholinyl, piperidiny! homopiperidinyl, or piperazinyl, wherein available ring nitrogens may be optionally substituted with C, ; alkyl, benzyl, C, acyl, C, ; alkylsulfonyl, or C,s alkoxycarbonyl; Ar represents a monocyclic or bicyclic aryl or heteroaryl ring, optionally substituted with between 1 and 3 substituents independently selected from halogen, C, s alkoxy, C, alkyl, C ,; alkenyl, cyano, azido, nitro, R#ZR®N, R*S0,, R#S, R*S0, R*0C=0, RZ?R*NC=0, C, 5 haloalkyl, Cs haloalkoxy, C,_; haloalkylthio, and C,_ alkylthio; R# is hydrogen, C, alkyl, C , alkenyl, phenyl, phenethyl, benzyl, or C heterocyclyl, C ,, acyl, aroyl, R®?0C=0, R®’R*NC=0, R¥S0, R*¥*S0,, R%S, or R®RZNSO,; R® is hydrogen, C,alkyl, C ,; alkenyl, phenyl, benzyl or C , 5 heterocyclyl; alternatively, R? and R® can be taken together to form an optionally substituted 4- to 7- membered heterocyclic ring, which ring may be

. saturated, unsaturated or aromatic; :

om . 30 each of R* and R*is C,alkyl, C , alkenyl, phenyl, benzyl, or C , “ heterocyclyl; R% and R” independently are hydrogen, C,salkyl, C , alkenyl, phenyl, benzyl, or C , 5 heterocyclyl;

or, alternatively, R* and R* can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;

. WwW represents O, S, NR¥, C=0, (C=0)NH, NH(C=0), CHR?, or a covalent eo, 5 bond; ‘ R? is H or OH and the dashed line is absent; or R* is absent where the dashed line is an sp? bond; R? is hydrogen, C,salkyl, C ,5 alkenyl, phenyl, naphthyl, benzyl, phenethyl, C ,; heterocyclyl, C ,; acyl, aroyl, R*0C=0, R¥R*NC=0, R*S0, R*S, R*S0,, or R*R*'NSO, ; or, alternatively, R*” and part of Ar, 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, NR®, NR™, N, SO,, C=0, and S; which ring may be saturated, unsaturated or aromatic; R%and R' are independently selected from H, C , ; alkyl, and -CH,CO,(C ,, alkyl); R#® is hydrogen, C, alkyl, C ,; alkenyl, hydroxy, phenyl, benzyl, C ,; heterocyclyl, R®0, R*R*'NC=0, R*S, R*S0, R¥*S0,, or R¥R*NSO,; R® is C,salkyl, C ,; alkenyl, phenyl, benzyl, or C , 5 heterocyclyl; R* and R* are independently selected from hydrogen, C, alkyl, C ,5 alkenyl, phenyl, benzyl, phenethyl, naphthyl, and C , 5 heteroaryl; alternatively, R* and R* 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 heterocarbyi groups, unless otherwise indicated, and in addition to any specified substituents, is . optionally and independently substituted with between 1 and 3 Cn 30 substituents selected from methyl, halomethyl, hydroxymethyl, halo, © hydroxy, amino, nitro, cyano, C ,; alkyl, C ,; alkoxy, -COOH, C ,; acyl, [di(C , alkyl)amino]C , alkylene, [di(C , alkyl)amino] C , alkyl-NH- CO-, and C ,; haloalkoxy;,

or a pharmaceutically acceptable salt, amide, or ester thereof; or a stereoisomeric form thereof. e 5 2 A compound of claim 1, wherein Ar, is selected from 5-7 membered ‘ monocyclic rings, and [5,6], [6,6], [6,5], and [5,5] fused bicyclic ring systems, said ring or ring system being carbocyclic or heterocyclic, saturated, unsaturated, or aromatic, optionally substituted with halo, C alkyl, C ,, haloalkyl, C ,, hydroxyalkyl, nitro, hydroxy, amino, mono- or di-(C , alkyl)amino, C ,, alkoxy, C ,, alkoxycarbonyl, C , acyl, C , acyloxy, C , alkylsulfonyl, C ,; alkoxycarbonylC ,_, alkoxy, cyano, and mono- or di-(C ,¢ alkyl)carbamoyl.

3. A compound of claim 1, wherein Ar, is selected from 2,5-di(C ,, alkyl)aminopyrrolyl and the following 6 formulae: WD R’ Ss R® N HA 7 To TO R20 (a) (b) (c) R? rR! ( Ko iN | if Y| 20 R3 =z BEN 77 vl ( b R ol (d) (e) (f) “ wherein each dashed line may be an sp? bond or absent;

X. is O, S,orN; and X,is O or §;

R is hydrogen, halogen, C,_ alkoxy, hydroxy, C,salkyl, C , alkenyl, cyano, nitro, R*R°N, C ,; acyl, C , 5 heterocyclyl, (C ,; heterocyclyl)C 5 . alkylene, R"'S, R"'S0O, R''SO,, R°OC=0, R°RNC=0, or R°RNSO,; or R' can be taken together with R* as provided below; “ R? is hydrogen, halogen, C,; alkoxy, hydroxy, C,s alkyl, C , alkenyl, cyano, nitro, R°R'N, C 5 heterocyclyl, or C ,, acyl; R® is hydrogen, halogen, C, ; alkoxy, hydroxy, C, salkyl, C , alkenyl, cyano, nitro, RR"N, C ,; acyl, C 5 heterocyclyl, R"OC=0, R°R"NC=0, or R°R"NSO,; R® is selected from hydrogen, C,salkyl, C , 5 alkenyl, phenyl, benzyl, phenethyl, C ,; heterocyclyl, C ,; acyl, aroyl, ROC=0, RRINC=0, R'2S0, R'*S0,, R'?S, and RIRINSO,; R® is selected from hydrogen, C, ;alkyl, C , alkenyl, phenyl, benzyl, phenethyl, C , heterocyclyl, C ,, acyl, aroyl, R*0C=0, R¥R*NC=0, R™®S0, R®S0,, RS, and R?R*NSO,; R™ is selected from hydrogen, C, alkyl, C ; alkenyl, phenyl, benzyl, phenethyl, C , 5 heterocyclyl, C ,; acyl, aroyl, R*0C=0, R*R*NC=0, R™S0, R”®S0,, RS, and R*R*NSO,; R° is selected from hydrogen, C, salkyl, C ,; alkenyl, phenyl, benzyl, phenethyl, C , ; heterocyclyl, C ,, acyl, aroyl, R®*0OC=0, R*R¥*NC=0, R™S0, R¥S0,, R™S, and R*R¥NSO,; each of R”, R', R", R?, R¥, R®¥, R¥, R¥, R®* , R¥, R*, and R*¥ is independently selected from hydrogen, C,salkyl, C ,; alkenyl, phenyl, benzyl, phenethyl, and C ,; heteroaryl; alternatively, R® and R®, R® and R, R™ and R", and R° and RP", independently, can be taken together to form an optionally substituted 4- to 7- membered heterocyclic ring, which ring may be saturated, A unsaturated or aromatic; eachof R", R" R™ R" R™ R* R", R®, and R* is independently C, alkyl, & C 5 alkenyl, phenyl, benzyl, phenethyl, or C, heterocyclyl; each of R° and RY, and R' and Ri are independently are hydrogen, C, alkyl, C ,5 alkenyl, phenyl, benzyl, phenethyl, or C, ; heteroaryl;

alternatively, R° and RY, and R' and R}, independently, can be taken together to form an optionally substituted 4- to 7- membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;

. Re is hydrogen, C, alkyl, C , 5 alkenyl, phenyl, benzyl, phenethyl, or C,s heterocyclyl, C, acyl, aroyl, R"OC=0, R"R"®NC=0, RS, R'"SO, ! R*S0O,, or R"R'NSO,; R" is hydrogen, C, alkyl, C , 5 alkenyl, phenyl, benzyl, phenethyl or C,; heterocyclyl; alternatively, R? and R" can be taken together to form an optionally substituted 4- to 7- membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic; R" and R' independently are hydrogen, C, alkyl, C ;5 alkenyl, phenyl, benzyl, or C, 5 heterocyclyl; alternatively, R"” and R*® can be taken together to form an optionally substituted 4- to 7- membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic; Y, is nitrogen or R*°C; Z is nitrogen or R?'C ; R* is hydrogen, halogen, C, alkoxy, C,salkyl, C , alkenyl, cyano, nitro, R™RN, C ,, acyl, R"OC=0, R"S, R"*S0, or R"“S0,; R* is hydrogen, halogen, C, salkoxy, C, alkyl, C , alkenyl, cyano, nitro, R°RPN, C ,; acyl, R"OC=0, R"'S, R"'SO, or R"'SO,; alternatively, R® and R® or R® and R* 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(C , 5 alkyl)amino, C , acyl, and C , 5 alkoxy;

R?¥ is hydrogen, C, alkyl, C , alkenyl, phenyl, naphthyl, benzyl, phenethyl, C5 heterocyclyl, C ,4 acyl, aroyl, R®0C=0, R¥R*NC=0, R®S0O, R*S, R*¥S0,, or R°R*NSO,; , or, alternatively, R”” and R'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, NR®, NR", N, SO,, C=0, and S; which ring may be saturated, unsaturated or aromatic; R®and R' are independently selected from H, C , ; alkyl, and -CH,COXC ,,

alkyl);

X; is CHR", =N-, NH, C=0, SO,, CHSR" wherein, in formula (f), R" is hydrogen, halogen, C, alkoxy, hydroxy, C, s alkyl, C , 5 alkenyl, cyano, nitro, R*R*N, C ,, acyl, C , 5 heterocyclyl, (C , heterocyclyl)C , 5 alkylene, R*'S, R*S0O, R*'S0,, R®0C=0, R¥*R*NC=0, R*R*NSO,, R"S0,- or R¥(C=0)0-;

Y; is CH, CHR? =CR?, O, or NR, wherein R” is H, C,, alkyl, C , alkenyl, C, acyl, C, ; heterocyclyl, (C,;heterocyclyl)-C, s alkylene, phenyl,

(phenyl)-C, alkylene, (C ,; cycloalkyl)-C, ; alkylene, (H,NCO)- C, alkylene, Cs haloalkyl, C,; cyanoalkyl, (C, 5 alkoxycarbonyl)C, 5 alkylene, and (phenylcarbonyl)NH-;

m isOor1; p isOor1;

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

R substituents selected from methyl, halomethyl, hydroxymethyl, halo,

hydroxy, amino, nitro, cyano, C ,; alkyl, C , alkoxy, -COOH, C ,; acyl,

- [di(C ,, alkyl)amino]C ,; alkylene, [di(C ,, alkyl)amino] C ,; alkyl-NH- CO-, and C ,; haloalkoxy.

4. A compound of claim 3, wherein Ar, is selected from formulae (e).

5. A compound of claim 3, wherein Ar, is selected from formulae (f).

6. A compound of claim 3, wherein Ar, is selected from formula (a)-(d). e -

7. A compound of claim 3, wherein R'is halogen, C,; alkoxy, hydroxy, C,s alkyl, cyano, nitro, R®°R°N or is taken together with RZ.

8. A compound of claim 7, wherein R'is taken together with R.

9. A compound of claim 8, wherein R' and R* taken together are selected from: a) ~CH,NR®-(C=0)- b) ~OCH(C=0)- c) —CH,CH,(C=0)- d) —-CH,-O(C=0)- e) —CH,S(C=0)- f) —O(C=0) - g) -CH,(C=0) - h) -NR*(C=0) - i) -NR%SO,)- i) -CH,NR°SO.- k) ~NR°CH,(C=0)- and [) - SCH,(C=0)-.

10. A compound of claim 9, wherein R' and R*¥ taken together are selected from: : a) ~CH,-(C=0)- b) ~O(C=0)- “ c) —-CH,CH,- d) -S(C=0)- e) -N=N-

f) -NR°SO,- g) -N=CR®- h) —-NR®(C=0)- and > i) ~CH=CH-. ' 11. A compound of claim 3, wherein R?is hydrogen, halogen, C,; alkoxy, C,salkyl, cyano, or R°R'N, where R® and R" are H or C 5 alkyl, or are taken together to form a 5-7 membered heterocyclic ring.

12. A compound of claim 3, wherein R® is hydrogen, halogen, C,; alkoxy,

C..s alkyl, cyano, nitro, or R°R"N, where R® and R" are H or C ,; alkyl, or are taken together to form a 5-7 membered heterocyclic ring.

13. A compound of claim 1, wherein R® and R® are independently selected from hydrogen and C, ; alkyl.

14. A compound of claim 12, wherein one of R® and R®is H.

15. A compound of claim 14, wherein R® and R® are each H.

16. A compound of claim 1, wherein one of R” and R® is H and the other is 5-7 membered carbocyclyl or heterocyclyl.

17. A compound of claim 1, wherein R” and R® are taken together to form an optionally substituted 5- to 7- membered carbocyclic or heterocyclic ring.

18. A compound of claim 16, wherein R” and R® taken together form a six- membered heterocyclyl.

19. A compound of claim 16, wherein R” and R® taken together form - pyridinyl, pyrimidinyl, or piperazinyl, optionally N-substituted with -(C=0)R?, -SO,R*, or -(C=0)NHR*.

20. A compound of claim 3, wherein each of R*,R®, R™, and R® is independently selected from hydrogen, C, alkyl, C ,4 acyl, and the respective ROC=0, RRNC=0, RSO, RSO,, and RRNSO, groups.

21. A compound of claim 19, wherein each of R?, R¢, R™, R°, R®, R, R", and ' RP is independently selected from hydrogen and C, alkyl; or, independently, R* and R®, R® and R', R" and R", and R° and R®, taken together, form an optionally substituted 4- to 7-membered carbocyclic or heterocyclic ring.

22. A compound of claim 21, wherein: (1) R® and R® taken together are independently morpholinyl, piperidinyl, or pyrrolidinyl; (2) R® and Rf taken together are morpholinyl, piperidinyl, or pyrrolidinyl; or (3) both (1) and (2) apply.

23. A compound of claim 3, wherein each of R°and R?, Rand R’, R*and R' is independently hydrogen or C, alkyl, alternatively, R® and R%, R' and Rj, and R*and R', independently, can be taken together to form an optionally substituted 4- to 7- membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic.

24. A compound of claim 23, wherein R° and R%, Rand R), and R*and R', independently, are taken together to form an optionally substituted 4- to 7- membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic.

25. A compound of claim 3, wherein each of R?, R', R", R®, R%¥, R®, R* R¥, R¥, R¥, R¥, and R* is independently H or C, alkyl.

26. A compound of claim 3, wherein each of R", R"2, R™ R", R", R™, R", . R®*, and R* is independently H or C, ; alkyl.

27. A compound of claim 3, wherein R? is C, alkyl, C ,, acyl, R7OC=0, R'RNC=0, RS, R"*SO, R'*S0O,, or R"R"NSO,; and R" hydrogen or C,s alkyl; alternatively, RY and R" can be taken together to form an . optionally substituted 4- to 7- membered heterocyclic ring. ‘ 28. A compound of claim 3, wherein R" and R" independently are hydrogen or C, 5 alkyl.

29. A compound of claim 1, wherein nis 1.

30. A compound of claim 1, wherein n is O.

31. A compound of claim 1, wherein G is C,_ alkanediyl, optionally substituted with hydroxy, halogen, (L)-C,;alkyloxy, or [(L)-C 5 alkylene]amino.

32. A compound of claim 31, wherein G is C, alkanediyl, optionally substituted with hydroxy, (L)-C,_; alkyloxy, or [(L)-C ,.; alkylene]amino.

33. A compound of claim 3, wherein each of R® and R* is independently selected from hydrogen, halogen, C,_; alkoxy, C, 5 alkyl, cyano, nitro, and R™R"N or R°RPN, respectively.

34. A compound of claim 33, wherein each of R® and R? is independently selected from hydrogen, halogen, C , ; alkyl, and R"R"N or R°RPN, respectively. :

35. A compound of claim 1, wherein Ar represents a monocyclic ring, optionally substituted with 1 to 2 substituents selected from halogen, C, alkyl, cyano, azido, nitro, R?R*N, halomethyl, and halomethoxy.

36. A compound of claim 35, wherein Ar is a six membered ring substituted with between 1 and 2 substituents independently selected from methyl,

halogen, CF,, and OCF,, said substituent or substituents being at the 4- position, or at the 3- and 4- positions, respectively. . 37. A compound of claim 1, wherein each of R*%, R%, and R* is hydrogen or

C,.s alkyl.

38. A compound of claim 1, wherein R* and R® independently are hydrogen or C, ; alkyl; or, alternatively, R® and R* can be taken together to form an optionally substituted 4- to 7- membered heterocyclic ring.

39. A compound of claim 38, wherein each of R® and R® is independently hydrogen or C, ; alkyl.

40. A compound of claim 1, wherein W is NRZ.

41. A compound of claim 1, wherein W is CHR?®, and R®is hydrogen or C, 5 alkyl.

42. A compound of claim 1, wherein RZis C, ;alkyl; or R* and R* are independently selected from hydrogen and C, alkyl, or R* and R* are taken together to form a 5-6 membered heterocyclyl.

43. A compound of claim 3, wherein Ar, isformula (e) and R' halogen, C,_;alkoxy, hydroxy, C,s alkyl, cyano, nitro, and R*R°N, or R' can be taken together with R¥ as provided below; R? is hydrogen, halogen, C, alkoxy, C, alkyl, or R°RN; i R® is hydrogen, halogen, C, alkoxy, hydroxy, C,salkyl, cyano, R°R"N; R®and R® are independently selected from hydrogen and C,_; alkyl;

CC . R” and R® 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 R*'R° , R™ , and R° is independently selected from hydrogen, C, s alkyl, C ,s acyl, and the respective ROC=0, RRNC=0, RS, RSO, RSO,, and RRNSO, groups; . each of R°, R",R", and RP, is independently selected from hydrogen and Cis alkyl; each of R", R*3, R®®, R", R'", R', R™, and R® is independently C, salkyl; each of R°and R?, R and R}, R*and R', R* and R*, R* and R* , R* and R¥ are independently are hydrogen or C, salkyl, or are taken together to form an optionally substituted 4- to 7- membered heterocyclic ring; R? is hydrogen, C,;alkyl, C ,, acyl, R"OC=0, R""R®*NC=0, RS, R'*SO, R"S0,, or R"R"®NSO,; R" is hydrogen or C, alkyl; alternatively, R® and R" can be taken together to form an optionally substituted 4- to 7- membered heterocyclic ring; R' and R'" independently are hydrogen or C, 5 alkyl; n isOor1; G is C,, alkenediyl or C,, alkanediyl, optionally substituted with hydroxy, halogen, C,salkyloxy, (L)-C,s alkoxy, N;, or [(L)-C , alkyleneJamino; L is amino, mono- or di-C, ; alkylamino, pyrrolidinyl, morpholinyl, piperidinyl homopiperidinyl, or piperazinyl, wherein available ring nitrogens may be optionally substituted with Cg alkyl, benzyl, C, ;alkylcarbonyl, or C, alkyloxycarbonyl;

Y. is nitrogen or R*C; Z, is nitrogen or R*'C ; R* and R* are independently selected from hydrogen, halogen, C, alkoxy,

C,.salkyl, cyano, nitro, and R™R"N or R°RPN, respectively; alternatively, R® and R® or R® and R* 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, C, alkoxy, C, salkyl, cyano, azido, nitro, R?R®*N, R*S0,, R*0C=0, R®R®NC=0, CF,, OCF,, CF,S, and C, alkylthio;

R*? is hydrogen, C, alkyl, phenyl, benzyl, phenethyl, C, ;heterocyclyl, C,, acyl, aroyl, R*OC=0, R®R*NC=0, R*S0, R*S0,, or R°R*NSO,; R® is hydrogen or C, salkyl; . alternatively, R?? and R* can be taken together to form an optionally substituted 4- to 7- membered heterocyclic ring; ’ R* is hydrogen or C, alkyl; R® and R?® are independently hydrogen or C, ; alkyl; or, alternatively, R® and R? can be taken together to form an optionally substituted 4- to 7- membered heterocyclic; W is NR¥or CHR%; R? is hydrogen, C, alkyl, R®0OC=0, R*R*NC=0, R®*S0, R#S0,, or R¥R¥NSO,; or, alternatively, R¥ and R' can be taken together to form an optionally substituted 5- or 6-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic; R#* is hydrogen, hydroxy, C, 5 heterocyclyl, phenyl, or C, alkyl; R#* is C,salkyl; and R* and R* are independently selected from hydrogen, C, salkyl; alternatively, R* and R* can be taken together to form an optionally substituted 4- to 7-membered heterocyclic.

44. A compound of claim 42, wherein R' and R? taken together are selected from: a) ~CH,NR®-(C=0)- b) —OCH,(C=0)- ¢) =CH,CH,(C=0)- d) ~CH,-O(C=0)- e) -CH,S(C=0)- f) ~O(C=0) - ’ 30 g) -CH,(C=0) - h) -NR%(C=0) - i) ~NR%(SO,) - j) -CH,NR°SO,-

k) ~NR°CH,(C=0)- and : 1) - SCH,(C=0)-. . 45. A compound of claim 42, wherein R' taken together with R,; are selected from: ' a) -CH_~(C=0)- b) -O(C=0)- c) —CH,CH,- d) -S(C=0)- e) -N=N- f) ~-NR°SO,- g) -N=CR*- h) -NR®*(C=0)- and i) -CH=CH-.

46. A compound of claim 1, wherein one of R° and R® is H, R” and R® 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, C, ; alkyl, cyano, azido, nitro, R#ZR®N, CF, and OCF,.

47. A compound of claim 46, wherein both R® and R® are each H, and Ar is a six membered ring substituted with between 1 and 2 substituents independently selected from halogen, methyl, CF;, and OCF,, said substituent or substituents being at the 4-position, or at the 3- and 4- positions.

48. A compound of claim 47, wherein R” and R® taken together form tetrahydropyridinyl, optionally N-substituted with -(C=O)R?, -SO,R*, or - (C=O)NHR“.

49. A compound of claim 5, wherein X; is C=0, SO,, or CHR", and Y, is O or NR? where Ris H, C ,; alkyl, C , heterocyclyl, C, ; cyanoalkyl, or (Cys alkoxycarbonyl)C, s alkylene.

50. A compound of claim 49, wherein R¥ is H, C ,; alkyl, ora C ,4 ' heterocyclyl.

51. A compound of claim 5, wherein X; is C=0, and Y; is O, CHR? or NR, where R%¥ is H, C 5 alkyl, C ,5 heterocyclyl, C, ; cyanoalkyl, or (C5 alkoxycarbonyl)C, s alkylene.

52. A compound of claim 51, wherein X; is C=0 and Y; is O.

53. A compound of claim 5, whereinmisOand pis O;misOand pis 1; or mis 1and pis O.

54. A compound of claim 53, wherein p is 0.

55. A compound of claim 1, wherein R* is H.

56. A compound of claim 1, wherein R* is OH.

57. A compound of claim 1, wherein R* is absent.

58. A compound of claim 3, wherein R® and R® taken together are a six- membered carbocyclic or heterocyclic ring optionally substituted with between 1 and 3 substituents independently selected from halo, C alkoxy, di(C 5 alkyl)amino, and C , acyl.

59. A compound of claim 3, wherein each of R® and R® is H.

60. A compound of claim 1, selected from: 1-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyi-phenyl)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-1,3- - dihydro-benzoimidazol-2-one ; 1-(1-{3-[3-(3,4-Dichloro-phenyl)-56-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2- one ; 3-(3,4-Dichloro-phenyl)-1-{3-[4-(2-ox0-2,3-dihydro-benzoimidazol-1-yl)- piperidin-1-yl]-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid amide ;

6-Chloro-1-(1-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yi]-propyt}-piperidin-4-yi)-1,3-dihydro- benzoimidazol-2-one ;

3-~(3,4-Dichloro-phenyl)-1-{3-[4-(3-methyl-2-0x0-2,3-dihydro-

benzoimidazol-1-yl)-piperidin-1-yl}-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3- c]pyridine-5-carboxylic acid amide ;

[3-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl})- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyli}-piperidin-4-yl)-2-oxo-2,3- dihydro-benzoimidazol-1-yi]-acetonitrile ;

[3-(1-{2-Hydroxy-3-[5-methanesulfonyi-3-(4-trifluoromethyl-phenyi)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-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-trifluoromethyi- phenyl)-4,5,6,7-tetrahydro-pyrazolo{4,3-c]pyridin-1-yij-propyi}-piperidin-4-yl)-1-

methyl-1,3-dihydro-benzoimidazol-2-one ;

1-{3-[4-(6-Chloro-3-methyl-2-ox0-2,3-dihydro-benzoimidazoi-1-yl)- piperidin-1-yl]-propyl}-3-(3,4-dichloro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3- c]pyridine-5-carboxylic acid amide ; ] 3-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yi)-1,5- Co dimethyl-1,3-dihydro-benzoimidazol-2-one ;

3-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yi]-propyl}-piperidin-4-yl)-1,3- dihydro-imidazo[4,5-b]pyridin-2-one ; . 3-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yi]-2-hydroxy-propyl}-piperidin-4-yl)-5-methoxy-1,3- ’ dihydro-imidazo[4,5-b]pyridin-2-one ; 3-(4-Bromo-phenyl)-1-{2-hydroxy-3-[4-(5-methoxy-2-oxo-1,2-dihydro- imidazo[4,5-b]pyridin-3-yl)-piperidin-1-yl]-propyi}-1,4,6,7-tetrahydro- pyrazolo[4,3-c]pyridine-5-carboxylic acid amide ;

3-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yi}-propyl}-piperidin-4-yl)-5-methoxy- 1-methyl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one ;

5-Dimethylamino-3-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4- trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-

piperidin-4-yl)-1,3-dihydro-imidazo[4,5-b]pyridin-2-one ;

6-Chloro-1-(1-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-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-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-y1)-3,4-

dihydro-1H-quinolin-2-one ;

4-(1-{3-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yi)-4H- benzo[1,4]Joxazin-3-one ;

1-(1-{3-[5-Methanesulfonyl-3~(4-trifluoromethyl-phenyl)-4,5,6,7- . tetrahydro-pyrazolof4,3-c]pyridin-1-yl]-propyl}-piperidin-4-y1)-3,4-dihydro-1H-

quinazolin-2-one .

61. A compound of claim 1, selected from: [3-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-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-pyrazolo[4,3- ) clpyridin-1-yl]-propyl}-piperidin-4-yl)-4H-benzo[1,4]oxazin-3-one.

62. A compound of claim 1, selected from: 2-(1-{3-[5-Acetyl-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-

10. c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-ylamino)-benzonitrile; 1~(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-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-pyrazolo[4,3- c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yi)-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-pyrazolo[4,3-c]pyridin-5-yl)-ethanone; 1-(3-(4-Chloro-3-methyl-phenyl)-1-{3-[4-(2,3-dihydro-indoi-1-yl)-piperidin- 1-yl]-2-hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone; (S)-1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hyd roxy-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- pyrazolo[4,3-c]pyridin-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- pyrazolo[4,3-c]pyridin-1-yi}-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-pyrazolof4,3-c]pyridin-1-ylj-propyl}-piperidin-4-yl)-2-oxo-2,3-dihydro- ) benzoimidazol-1-yl]-acetonitrile; .

5-Chloro-3-(1-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yi]-propyl}-piperidin-4-yl}-1-methyl-1,3- dihyd ro-benizoimidazol-2-one; . 1-(1-{3-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-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)- [1,2,4]oxadiazol-5-yl}-piperidin-1-yi}-2-hydroxy-propyl)-1,4,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-5-yl}-ethanone; 1-[1-{2-Hydroxy-3-[4-(5-trifluoromethyl-benzothiazol-2-yl)-piperidin-1-yl}- propyi}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo(4,3-c]pyridin-5- _yll-ethanone; 1-[1-{3-[4-(Benzo[d]isoxazol-3-yloxy)-piperidin-1-y{]-2-hydroxy-propyi}-3- (4-trifiuoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-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-pyrazolo[4,3-c]pyridin-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-pyrazolo[4,3-c]pyridin-5-yl]- ethanone; 1-[1-{3-[4-(3,5-Dichloro-pyridin-4-yloxy)-piperidin-1-yl]-2-hydroxy-propyi}- 3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}- ethanone; 1-[1-{3-[4-(1H-Benzoimidazol-2-yl)-piperidin-1-yl}-2-hydroxy-propyl}-3-(4- trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 6-Chloro-4-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl- phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)- } 4H-benzo[1,4]oxazin-3-one; 6-Chloro-1-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl- phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)- . 3,4-dihydro-1H-quinolin-2-one;

8-Chloro-1-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl- phenyi)-4,5,6,7-tetrahydro-pyrazolo{4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)- 3,4-dihydro-1H-quinazolin-2-one; : 1-[4-(6-Chloro-2,2-dioxo-3,4-dihydro-2H-2A°-benzo[1,2,6]thiadiazin-1-yl)- piperidin-1-yl}-3~[5-methanesulfonyl-3-(4-trifluoromethyi-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propan-2-ol; 4-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-4H- pyrido[3,2-b]{1,4]Joxazin-3-one; 5-Chloro-~1-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl- phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyi}-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-pyrazolo[4,3-c}pyridin-1-yl]-propan-2- ol 1-(1-{3-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyi}-piperidin-4-yl)-1H-benzotriazole; 1-{3-[4-(3-Methyl-2-ox0-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl]- propyl}-3-(4-trifiuoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine- 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-benzo[1,4]oxazin-3-one; (S)-1-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-3-methyi- 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-pyrazolo[4,3-c]pyridin-1-yl}-propyl}- piperidin-4-yl)-1-methyl-1,3-dihydro-imidazof4,5-b]pyridin-2-one.

63. A compound of claim 1, selected from:

1-(1-{3-[5-Methanesuifonyl-3-(4-trifluoromethyl-phenyi)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yi)-octahydro- benzoimidazol-2-one; : 1-(1-{3-[5-Acetyl-3-(3,4-dichloro-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yi)-octahydro-benzoimidazol-2-one; ' Acetic acid 1-(1-{3-[5-acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yi}-propyl}-piperidin-4-yl)-1H-benzoimidazol-2-yi ester; Methanesulfonic acid 1-(1-{3-[3-(4-bromo-phenyl)-5-methanesuifonyi- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-1H- benzoimidazol-2-yl ester; 1-(1-{3-[56-Acetyl-3-(3,4-dichloro-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4, 3- clpyridin-1-yl}-propyl}-piperidin-4-yl)-5-chloro-1,3-dihydro-indol-2-one; 1-{3-[4-(5-Chloro-2-oxo0-2,3-dihydro-indol-1-yl}-piperidin-1-yl}-propyl}-3- (3,4-dichloro-phenyl)-1,4,6,7-tetrahydro-pyrazolof4,3-c]pyridine-5-carboxylic acid amide; 1-{3-[4-(5-Chloro-2-oxo0-2,3-dihydro-indol-1-yl)-piperidin-1-yl}-propyl}-3- (3,4-dichloro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid methylamide; Acetic acid 1-(1-{3-[5-acetyl-3-(3,4-dichloro-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-1H-benzoimidazol-2-yl ester; Methanesulfonic acid 1-(1-{3-[3-(3,4-dichloro-pheny})-5- methanesulfonyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyl}- piperidin-4-yl)-1H-benzoimidazol-2-y! ester, 1-[1-{3-[4~(3,5-Dichloro-pyridin-4-ylamino)-piperidin-1-yl}-2-hydroxy- propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5- yll-ethanone; 1-[1-{3-[4-(Benzooxazol-2-yloxy)-piperidin-1-yl}-2-hydroxy-propyl}-3-(4- trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yi}-ethanone; , 1-[1-{3-[4-(Benzooxazol-2-ylamino)-piperidin-1-yil-2-hydroxy-propyl}-3- (4-trifluoromethyl-phenyi)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-ylj- , ethanone; and

1-(4-Benzooxazol-2-yl-piperidin-1-yl)-3-[5-methanesulfonyl-3-(4- triflucromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propan-2-

ol.

64. A compound of claim 1, selected from: 1-(4-Benzothiazol-2-yl-piperidin-1-yl)-3-[5-methanesulfonyl-3-(4- trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propan-2- - ol; 1-{3-[4-(5-Methyl-3-ox0-2,3-dihydro-benzo[1,4]oxazin-4-yl)-piperidin-1- ' yll-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3- c]pyridine-5-carboxylic acid amide; N-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-N-(3-chloro- phenyl)-benzamide; 4-(1-{3-[5-Acetyl-3~(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yi]-propyl}-piperidin-4-yl)-5-methyl-4H- benzo[1,4]Joxazin-3-one; 4-(1-{3-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-5-methyl-4 H- benzo[1,4]oxazin-3-one; 3-(4-Bromo-phenyl)-1-{3-[4-(5-methyl-3-ox0-2,3-dihydro- benzo[1,4]oxazin-4-yl)-piperidin-1-yl]-propyi}-1,4,6,7-tetrahydro-pyrazolo[4,3- c]pyridine-5-carboxylic acid amide; 4-(1-{3-[6-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yll-propyl}-piperidin-4-yl)-5-methyl-4H-benzo[1,4]oxazin-3-one; 4-(1-{3-[3-(4-Bromo-phenyi}-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-propyi}-piperidin-4-yl)-5-methyl-4H- benzo[1,4]oxazin-3-one; 3-(4-Bromo-phenyl)-1-{3-[4-(6-ethanesulfonyl-3-oxo-2,3-dihydro- benzo[1,4]Joxazin-4-yl)-piperidin-1-yi]-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3- c]pyridine-5-carboxylic acid amide; 4-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- i c]pyridin-1-yl]-propyl}-piperidin-4-yl)-6-ethanesulfonyl-4H-benzo[1,4]oxazin-3- one;

. 4-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yi]-propyi}-piperidin-4-yl)-6-ethanesulfonyl-4H- benzo[1,4Joxazin-3-one;

1-[1-[3-(4-Benzothiazol-2-yl-piperidin-1-yl)-2-hydroxy-propyl}-3-(4-chloro- 3-methyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}-ethanone; 1-[1-[3-(4-Benzothiazol-2-yl-piperidin-1-yl)-2-hydroxy-propyl]-3-(4- : trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolof4,3-c]pyridin-5-ylj-ethanone; 1-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-3,4- dihydro-1H-quinolin-2-one; 1-(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-3,4- dihydro-1H-quinolin-2-one; 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yi]-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-3,4-dihydro-1H- quinolin-2-one; 1-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-3,4- dihydro-1H-quinazolin-2-one; 1-(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-3,4- dihydro-1H-quinazolin-2-one;

1-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-3-[4-(6-chloro-2,2-dioxo-3,4-dihydro-2H-2)°-2,1,3- benzothiadiazin-1-yl)-piperidin-1-yl}-propan-2-ol;

1-[4-(6-Chloro-2,2-dioxo-2,3-dihydro-2A°-2,1,3-benzothiadiazol-1-yl)- piperidin-1-yl]-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propan-2-ol; 1-[1-{3-[4-(6-Chloro-2,2-dioxo-2,3-dihydro-2).°-2,1,3-benzothiadiazol-1- yl)-piperidin-1-yll-2-hydroxy-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; : 4-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- : pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-4-1,4-benzoxazin- ’ 3-one;

1-(1 ~{3-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyi )-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-3,4-dihydro-1H- quinolin-2-one; - 1-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolof4,3-c] pyridin-1 -yl]-2-hydroxy-propyl}-piperidin-4-yl)-3,4-dihydro-1H- ’ quinolin-2-one; 4-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yi}-4H-1,4- benzoxazin-3-one; 4-(1-{3-[6-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolof4,3-c]pyridin-1 -yi]-2-hyd roxy-propyl}-piperidin-4-yl)-4H-1,4- benzoxazin-3-one; 1-(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yi]-2-hydroxy-propyl}-piperidin-4-yl)-3,4-dihydro-1H- quinolin-2-one; 1-{2-Hydroxy-3-[4-(2-ox0-3,4-dihydro-2H-quinolin-1-yl)-piperidin-1-yl}- propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine- 5-carboxylic acid tert-butyl ester; : 1-{2-Hydroxy-3-[4-(3-ox0-2,3-dihydro-1,4-benzoxazin-4-yl)-piperidin-1- yl]-propyl}-3-(4-trifluoromethyl-phenyi)-1,4,6,7-tetrahydro-pyrazolo[4,3- c]pyridine-5-carboxylic acid tert-butyl ester; 4-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-4H-1 ,4- benzoxazin-3-one; and 4-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-4H-1,4-benzoxazin-3-one.

65. A compound of claim 1, selected from: 1-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolof4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-3,4-dihydro-1H-quinolin-2- ) one;

1-{3-{4-(2-Ox0-3,4-dihyd ro-2H-quinolin-1 -yl)-piperidin-1-yl}-propyi}-3-(4- trifiuoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester; : 1-{3-[4-(3-Ox0-2,3-dihydro-1,4-benzoxazin-4-yl)-piperidin-1-yl}-propyi}-3- (4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5- ' carboxylic acid tert-butyl ester; 6-Chloro-4-(1-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1 -yl]-propyl}-piperidin-4-yl)-4H-1 4- benzoxazin-3-one; 4-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yi]-propyl}-piperidin-4-yl)-6-chloro-4H-1,4-benzoxazin- 3-one; 4-(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-4H-1,4-benzoxazin-3-one; 1-(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6, 7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yij-propyi}-piperidin-4-yli)-3,4-dihydro-1H-quinolin-2- one; 4-(1-{3-[6-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-4H-1,4-benzoxazin-3-one; 1-(1-{3~[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yi]-2-hydroxy-propyli}-piperidin-4-yl)-3,4-dihydro-1H-quinolin-2-one; 1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolof4,3-c]pyridin-1-yi]-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro-indol- 2-one; 1-(1-{3-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyi)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yi)-1,3-dihydro-indol- 2-one; 1-(1-{3-[5-Acetyl-3-(3-chloro-4-methyl-phenyl)-4,5,6,7-tetrahydro-

. pyrazolo{4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro-indol- 2-one; , 1-(1-{3-[3-(4-Chloro-3-methyl-phenyl)-5-methanesulfonyl-4,5,6,7- : tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-1,3- dihydro-indol-2-one;

1-(1-{3-[5-Acetyi-3-(4-trifluoromethyi-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro-indol- 2-one; . 1-(1-{3-[5-Acetyl-3-(4-nitro-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro-indol-2-one; 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolof4,3- c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro-indol-2-one; 1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-1,3- : 10 dihydro-indol-2-one; 6-Chloro-1-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl- phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)- 1,3-dihydro-indol-2-one; 1-(1-{3-[6-Acetyi-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro-

pyrazolo[4,3-c]pyridin-1-yi]-2-hydroxy-propyl}-piperidin-4-yl)-5-chloro-1,3-

dihydro-indol-2-one; 5-Chloro-1-(1-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yi}-propyl}-piperidin-4-yl)-1,3-dihydro-indol- 2-one;

1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- clpyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-5-chloro-1,3-dihydro-indol-2- one;

1-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-5-chloro-1,3-

dihydro-indol-2-one;

4-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo{4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yi)-4 H-pyrido[3,2-b]- 1,4-oxazin-3-one; 1-(1-{2-Hydroxy-3-[6-methanesulfonyl-3-(4-trifluoromethyl-phenyl)- 4,5,6,7-tetrahydro-pyrazolo[4,3-cjpyridin-1-yl}-propyl}-piperidin-4-yl)-1,5- . dihydro-4,1-benzoxazepin-2-one;

1-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyi)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-1,4- dihydro-3,1-benzoxazin-2-one; . 1-(1-{3-[3-(4-Bromo-phenyl}-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-1,4-dihydro-3,1- ’ benzoxazin-2-one; 1-(1-{2-Hydroxy-3-[56-methanesulfonyl-3-(4-trifluoromethyi-phenyl)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-1,5-~ dihydro-4,1-benzoxazepin-2-one; 1-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-1,4- dihydro-3,1-benzoxazin-2-one; 1-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-1,4-dihydro-3,1- benzoxazin-2-one; 1-(3-(4-Chloro-3-methyl-phenyl)-1-{2-hydroxy-3-[4-(5-nitro-2,3-dihydro- indol-1-yl)-piperidin-1-yl}-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)- ethanone; 1-(3-(4-Chloro-3-methyl-phenyi)-1-{2-hydroxy-3-{4-(6-nitro-2,3-dihydro- indol-1-yl)-piperidin-1-yl}-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)- ethanone; 1 -(3-(4-Chloro-3-methyl-phenyl)-1 -{2-hydroxy-3-[4-(2-methyl-2,3- dihydro-indol-1-yl}-piperidin-1-yl]-propyl}-1 4.6,7-tetrahyd ro-pyrazoloj4,3- c]pyridin-5-yl)-ethanone; 1-(1-{2-Hydroxy-3-{5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-3,4- dihydro-1H-quinazolin-2-one, 1-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-3,4-dihydro-1H- quinazolin-2-one;

. 1-(1-{3-[5~Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1 -yi]-2-hydroxy-propyi}-piperidin-4-yl)-3,4-dihydro-1H- quinazolin-2-one;

1-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yi}-propyl}-piperidin-4-yl)-3,4-dihydro-1H-quinazolin-2- one; . 1-(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6, 7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-y1)-3,4-dihydro-1 H-quinazolin-2- A one; 1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo{4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-1-(3-chioro- phenyl)-3-methyl-urea; 1-[3-(4-Benzotriazol-1-yl-piperidin-1-yl)-2-hydroxy-propyl}-3-(3,4- dichloro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester; 1-{3-[4-(5-Chloro-2-ox0-2,3-dihydro-indol-1-yl)-piperidin-1-yl]-propyl}-3- (3,4-dichloro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester; 5-Chloro-1-(1-{3-[3-(3,4-dichloro-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-1,3-dihydro-indol-2-one; 1-{3-[4-(5-Methyl-3-ox0-2,3-dihydro-benzo[1,4]oxazin-4-yl)-piperidin-1- yl}-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3- c]pyridine-5-carboxylic acid tert-butyl ester; and 3-(4-Bromo-phenyl)-1-{3-[4-(5-methyl-3-ox0-2,3-dihydro- benzo[1,4]oxazin-4-yl)-piperidin-1-yl}-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3- c]pyridine-5-carboxylic acid tert-butyl ester.

66. A compound of claim 1, selected from: : 3-(4-Bromo-phenyt)-1-{3-[4-(6-ethanesulfonyl-3-oxo-2,3-dihydro- benzo[1,4]oxazin-4-yl)-piperidin-1-yl]-propyi}-1,4,6,7-tetrahydro-pyrazolof4,3- c]pyridine-5-carboxylic acid tert-butyl ester; ) 1-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-3-[4-(5-triflucromethyl-benzothiazol-2-yi)-piperidin- » 1-yl]-propan-2-ol; 5-Methyl-4-(1-{3-[3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl}-4H-benzo[1,4]oxazin-3-one;

4-(1-{3-[3-(4-Bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1- vi}-propyl}-piperidin-4-yl)-5-methyl-4H-benzo[1,4]oxazin-3-one; 4-(1-{3-[3-(4-Bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1- n yl]-propyl}-piperidin-4-yl)-6-ethanesulfonyl-4H-benzo([1,4]Joxazin-3-one; 1-{3~[4-(6-Chlioro-indol-1-yi)-piperidin-1-yl]-propyl}-5-methanesuifonyl-3- ) (4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine; 3-(4-Bromo-phenyl)-1-{3-[4-(2-oxo0-3,4-dihydro-2H-quinolin-1-yl)- piperidin-1-yl]-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester;

: 10 3-(4-Bromo-phenyl)-1-{2-hydroxy-3-[4-(2-ox0-3,4-dihydro-2H-quinolin-1- yh)-piperidin-1-yl]-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester;

3-(4-Bromo-phenyl)-1-{2-hydroxy-3-[4-(3-ox0-2,3-dihydro-1,4- benzoxazin-4-yl)-piperidin-1-yi}-propyl}-1,4,6,7-tetrahydro-pyrazolof4,3- c]pyridine-5-carboxylic acid tert-butyl ester; 1-(1-{3-[3-(4-Trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolof4,3- clpyridin-1-yl]-propyl}-piperidin-4-yl)-3,4-dihydro-1H-quinolin-2-one; 3-(4-Bromo-phenyl)-1-{3-[4-(3-o0x0-2,3-dihydro-1 ,4-benzoxazin-4-yl)- piperidin-1-yl]-propyi}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester, 1-(1-{2-Hydroxy-3-[3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl}-3,4-dihydro-1H-quinolin-2- one; 4-(1-{3-[3-(4-Trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yl]-propyl}-piperidin-4-yl)-4H-1,4-benzoxazin-3-one; 1-(1-{3-[3-(4-Bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1- yl]-propyl}-piperidin-4-yl)-3,4-dihydro-1H-quinolin-2-one; 4-(1-{3-[3-(4-Bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1- ; yl}-propyl}-piperidin-4-yl)-4H-1,4-benzoxazin-3-one; 1-(1-{3-[3-(4-Bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1- ; yl]-2-hydroxy-propyl}-piperidin-4-yl)-3,4-dihydro-1H-quinolin-2-one; 4-(1-{3-[3-(4-Bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1- yl]-2-hydroxy-propyl}-piperidin-4-yl)-4H-1,4-benzoxazin-3-one;

4-(1-{2-Hydroxy-3-[3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-4H-1,4-benzoxazin-3-one; 1-(3-(3,4-Difluoro-phenyl)-1-{3-[4-(2,3-dihydro-indol-1-yl)-piperidin-1-yl]- , 2-hydroxy-propyi}-1,4,6,7-tetrahydro-pyrazolo[4,3-c}pyridin-5-yl)-ethanone; 1-[1-{3-[4-(5-Bromo-2,3-dihydro-indol-1-yl)-piperidin-1-yl]-2-hydroxy- ) propyl}-3-(4-chloro-3-methyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin- 5-yl]-ethanone; 1-(1-{3-[5-Acetyl-3-(3,4-difluoro-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro-indol-2-one;

1-[1-{3-[4-(5-Bromo-2,3-dihydro-indol-1-yl)-piperidin-1-yl}-2-hydroxy- propyl}-3-(3,4-difluoro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}- ethanone;

1-(1-{3-[3-(4-Bromo-phenyl})-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1- yl]-2-hydroxy-propyl}-piperidin-4-yi)-3,4-dihydro-1H-quinazolin-2-one;

1-(1-{3-[3-(4-Trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yl}-propyl}-piperidin-4-yl)-3,4-dihydro-1H-quinazolin-2-one;

1-(1-{3-[3~(4-Bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1- yl]-propyl}-piperidin-4-yl)-3,4-dihydro-1H-quinazolin-2-one; 1-(3-(4-Chloro-phenyl)-1-{3-[4-(3-chloro-phenylamino)-piperidin-1-yl]}-2-

hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)}-ethanone;

N-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c}pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-N-(3-chloro- phenyl)-acetamide;

1-(4-Benzoimidazol-1-yl-piperidin-1-yl)-3-[5-methanesulfonyl-3-(4-

trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolof4,3-c]pyridin-1-yi}-propan-2- ol;

1-(3-(4-Chloro-phenyl)-1-{2-hydroxy-3-[4-(2-methoxy-phenylamino)- piperidin-1-yl]-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone;

1-(3-(4-Chloro-phenyl)-1-{3-[4-(2-fluoro-phenylamino)-piperidin-1-yl]-2- hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone; . 1-{3-(4-Chloro-phenyl)-1-[2-hydroxy-3-(4-phenylamino-piperidin-1-yi)- propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}-ethanone;

1-(3-(4-Chloro-phenyl)-1-{3-[4-(4-chloro-phenylamino)-piperidin-1-yl}-2- hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolof4,3-c]pyridin-5-yl)-ethanone; 1-[1-{3-[4-(4-Bromo-phenylamino)-piperidin-1-yl}-2-hydroxy-propy!}-3-(4- . chloro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 4-(1-{3-[5-Acetyl-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- ' cJpyridin-1-yl)-2-hydroxy-propyl}-piperidin-4-ylamino)-benzonitrile; 1-{3-(4-Chloro-phenyl)-1 -[2-hydroxy-3-(4-p-tolylamino-piperidin-1 -yl)- propyl]-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}-ethanone; 1-(3-(4-Chloro-phenyl)-1-{2-hydroxy-3-[4-(4-methoxy-phenylamino)- : 10 piperidin-1-yl]-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone; 1-(3-(4-Chloro-phenyl)-1-{2-hydroxy-3-[4-(3-methoxy-phenylamino)- piperidin-1-yl]-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone; 1-(3-(4-Chloro-phenyl)-1-{3-[4-(3,5-dimethoxy-phenylamino)-piperidin-1- yl}-2-hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone; 1-[1-{3-[4-(5-Chloro-2-methyl-phenylamino)-piperidin-1-yl}-2-hydroxy- propyl}-3-(4-chloro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yi]- ethanone; 1-(3-(4-Chloro-phenyl)-1-{3-[4-(3-chloro-phenylamino)-piperidin-1-yl]-2- hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone; [2-(1-{3-[3-(4-Bromo-phenyl)-5-carbamoyl-4,5,6, 7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-ylamino)-4-ethanesulfonyl- phenoxyl-acetic acid methyl ester; [2-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yl}-propyl}-piperidin-4-ylamino)-4-ethanesulfonyl-phenoxy]-acetic acid methyl ester; [2-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-ylamino)-4-ethanesulfonyl- phenoxyl-acetic acid methyl ester; and 3-(4-Bromo-phenyi)-1-{3-[4-(5-ethanesulfonyl-2- methoxycarbonyimethoxy-phenylamino)-piperidin-1-yi]-propyl}-1,4,6,7-

. tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester.

67. A compound of claim 1, selected from: 2-(1 -{3-[3-(4-Bromo-phenyl)-4,5,6, 7-tetrahyd ro-pyrazolo[4,3-c]pyridin-1- yl}-propyl}-piperidin-4-ylamino)-4-ethanesulfonyl-phenoxy}-acetic acid methyl . ester; 1-{3-(4-Bromo-phenyl)-1-[2-hydroxy-3-(4-o-tolyloxy-piperidin-1-yl)- ; propyl]-1,4,6,7-tetrahydro-pyrazolo[4,3-clpyridin-5-yl}-ethanone; 1-{3-(4-Bromo-phenyl}-1-[2-hydroxy-3-(4-phenoxy-piperidin-1-yl)-propyl]- 1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}-ethanone; 1-{3-(4-Bromo-phenyl)-1-{2-hydroxy-3-(4-p-tolyloxy-piperidin-1-yl)- propyl]-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}-ethanone; 1-(3-(4-Bromo-phenyl)-1-{2-hydroxy-3-[4-(4-methoxy-phenoxy)-piperidin- 1-yll-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone; 1-(3-(4-Bromo-phenyl)-1-{3-[4-(4-chloro-phenoxy)-piperidin-1-yl]-2- hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone; 1-(3-(4-Bromo-phenyl)-1-{3-[4-(3-chloro-phenoxy)-piperidin-1-yl}-2- hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone; 1-(3-(4-Bromo-phenyl)-1-{3-[4-(3,4-dichloro-phenoxy)-piperidin-1-yl]-2- hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone; 1-{3-(4-Chloro-3-methyl-phenyi)-1-[2-hydroxy-3-(4-phenoxy-piperidin-1- yl)-propyl]-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}-ethanone; 3-(4-Chloro-3-methyl-phenyi)-1-[2-hydroxy-3-(4-p-tolyloxy-piperidin-1-yi)- propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}-ethanone; 1-(3-(4-Chloro-3-methyl-phenyl)-1-{2-hydroxy-3-[4-(4-methoxy-phenoxy)- piperidin-1-yl}-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone; 1-(3-(4-Chloro-3-methyl-phenyl)-1-{3-[4-(4-chloro-phenoxy)-piperidin-1- yl}-2-hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone; 1-(3-(4-Chloro-3-methyl-phenyl)-1-{3-[4-(3-chloro-phenoxy)-piperidin-1- yl}-2-hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yi)-ethanone; , 1-{3-(4-Chloro-3-methyl-phenyl)-1-[2-hydroxy-3-(4-o-tolyloxy-piperidin-1- yl)-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}-ethanone; , 1-(3-(4-Chloro-3-methyl-phenyl)-1-{3-[4-(3,4-dichloro-phenoxy)-piperidin- ~ 1-yl}-2-hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone;

2-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyi}-piperidin-4-yloxy)-benzonitrile; 2-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- - c]pyridin-~1-yl}-2-hydroxy-propyl}-piperidin-4-yloxy)-benzonitrile; 1-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- ; pyrazolo[4,3-c]pyridin-1-yi]-3-[4-(4-chloro-phenoxy)-piperidin-1-yl]-propan-2-ol; 1-[1-{3-[4-(4-Chloro-phenoxy)-piperidin-1-yl]-2-hydroxy-propyl}-3-(4- trifuoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}-ethanone; 1-(1-{3-[5-Acetyl-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-

c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yi}-1,3-dihydro-benzoimidazol-2-

one; 1-{1-[3-(5-Acetyl-3-phenyl-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl)- 2-hydroxy-propyll-piperidin-4-yi}-1,3-dihydro-benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(4-trifluoromethoxy-phenyi)-4,5,6,7-tetrahydro-

pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro- benzoimidazol-2-one;

1-(1-{3-[5-Acetyl-3-(4-iodo-phenyl)-4,5,6, 7-tetrahydro-pyrazolof4,3- c}pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2- one;

1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro- benzoimidazol-2-one;

1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yi]-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2-

one;

1-(1-{3-[5-Acetyl-3-(4-chloro-3-nitro-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro- benzoimidazol-2-one; ) 1-(1-{3-[5-Acetyl-3-(4-trifluoromethylsulfanyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyi}-piperidin-4-yl)-1,3-dihydro- N benzoimidazol-2-one;

1-(1-{3-[5-Acetyl-3-(4-methanesulfonyl-phenyi)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro- benzoimidazol-2-one; . 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- CJpyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-1,3-dihydro- ’ benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-3-methyl-1,3- dihydro-benzoimidazol-2-one;

1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-3-ethyl-1,3- dihydro-benzoimidazol-2-one;

1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyi}-piperidin-4-yl)-3-isopropyl-1,3-

dihydro-benzoimidazol-2-one;

1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-3-butyl-1,3- dihydro-benzoimidazol-2-one;

1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro-

pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-3-benzyi-1,3- dihydro-benzoimidazol-2-one;

1-(1-{3-[5-Acetyl-3-(4-iodo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- clpyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-5-fluoro-1,3-dihydro- benzoimidazol-2-one;

3-(1-{3-[56-Acetyl-3-(4-iodo-phenyl)-4,5,6,7-tetrahydro-pyrazolof4,3- c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-7-fluoro-2-oxo-2,3-dihydro-1H- benzoimidazole-4-carbonitrile;

1-(1-{3-[6-Acetyl-3-(4-iodo-phenyl)-4,5,6, 7-tetrahydro-pyrazolo[4,3- , c]pyridin-1-yl}-2-hydroxy-propyi}-piperidin-4-yl)-6-fluoro-1,3-dihydro- benzoimidazol-2-one; . 3-(1-{3-[5-Acetyl-3-(4-iodo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- * ¢]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-2-oxo-2,3-dihydro-1H- benzoimidazole-5-carbonitrile;

1-{2-Hydroxy-3-[4-(2-ox0-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl]- propyi}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine- 5-carboxylic acid amide; - 1-(1-{3-[3-(4-Chloro-3-methyl-phenyl)-5-methanesulfonyl-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yi}-2-hydroxy-propyl}-piperidin-4-yt)-1,3- ) dihydro-benzoimidazoi-2-one; 3-(4-Chloro-3-methyl-phenyl)-1-{2-hydroxy-3-[4-(2-0x0-2,3-dihydro- benzoimidazol-1-yl)-piperidin-1-yl]-propyl}-1,4,6,7-tetrahydro-pyrazolo{4,3- clpyridine-5-carboxylic acid methylamide; 3-(4-Chloro-3-methyl-phenyl)-1-{2-hydroxy-3-f4-(2-ox0-2,3-dihydro- benzoimidazol-1-yl)-piperidin-1-yl]-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3- c]pyridine-5-carboxylic acid ethylamide; * 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolof4,3- clpyridin-1-yl-2-hydroxy-propyl}-piperidin-4-yl)-5-methyl-1,3-dihydro- benzoimidazol-2-one; and 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-6-methyl-1,3-dihydro- benzoimidazol-2-one.

68. A compound of claim 1, selected from: 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yl]-2-hydroxy-propyi}-piperidin-4-yl)-5,6-dichloro-1,3-dihydro- benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yi)-5-methyi-1,3- dihydro-benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yi)-6-methyl-1,3- . dihydro-benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro-

. pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-5,6-dichloro-1,3- dihydro-benzoimidazol-2-one;

1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-1,3- dihydro-benzoimidazol-2-one; : 1-(1-{3-[5-Acetyl-3-(4-chloro-3-triflucromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro- ’ benzoimidazol-2-one; 1-(1-{3-[3-(4-Chloro-3-methyl-phenyl)-5-methanesulfonyl-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yi]-2-hydroxy-propyl}-piperidin-4-yi)-3-(2- morpholin-4-yl-ethyl)-1,3-dihydro-benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(3-fluoro-4-trifiuoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro- benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(4-bromo-3-methyl-phenyl)-4,5,6,7-tetrahydro- : pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro- benzoimidazol-2-one; (R)-1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro- benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazoloj4,3- c]pyridin-1-yl}-2~-hydroxy-propyl}-piperidin-4-yl)-5-methoxy-1,3-dihydro- benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo}4,3- c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-7-chloro-1,3-dihydro- benzoimidazol-2-one; 3-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro-imidazo[4,5- b)pyridin-2-one; 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-

. clpyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-7-methyl-1,3-dihydro- benzoimidazol-2-one;

. (R)-1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yi)-6-chioro-1,3- dihydro-benzoimidazol-2-one;

1-(1-{3-[5-Acetyl-3-(3,4-dichloro-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- clpyridin-1-yi]-2-hydroxy-propyli}-piperidin-4-yi)-1,3-dihydro-benzoimidazol-2- one; , 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]Jpyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2- : one; 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4, 3- clpyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-1,3-dihydro- benzoimidazol-2-one; : 10 (S)-1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-1,3- dihydro-benzoimidazol-2-one; (R)-1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl}-1,3-dihydro- benzoimidazol-2-one; (R)-1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolof4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-6-chloro-1,3- dihydro-benzoimidazol-2-one; 2-{2-[3-(1-{3-[5-Acetyl-3-(4-chioro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yi}-2-hydroxy-propyl}-piperidin-4-yl)-2-oxo-2,3-dihydro- benzoimidazol-1-yl}-ethyl}-isoindole-1,3-dione; 1-(1-{3-[56-Acetyi-3-(4-chloro-3-methyl-phenyl)-4,5,6, 7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-3-(2-amino-ethyl)- 1,3-dihydro-benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyi)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yi)-3-methyl-1,3-dihydro- benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-

. clpyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-3-ethyl-1,3-dihydro- benzoimidazol-2-one;

. 1-(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yi)-3-methyl-1,3- dihydro-benzoimidazol-2-one;

1-(1-{3-[5-Acetyl-3-(4-triftuoromethyl-phenyi)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yi )-3-ethyl-1,3- dihydro-benzoimidazol-2-one;

. 6-Chloro-1-(1-{3-[3-(4-chloro-3-methyl-phenyl)-5-methanesulfonyl- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)- ‘ 1,3-dihydro-benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(3-chloro-4-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yi}-2-hydroxy-propyi}-piperidin-4-yl)-1,3-dihydro- benzoimidazol-2-one; 3-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-5-chloro-1-(2- morpholin-4-yl-ethyl)-1,3-dihydrobenzoimidazol-2-one; [3-(1-{3-[6-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl}-2-oxo-2,3-dihydro- benzoimidazol-1-yi]-aceticacid ethyl ester; 1-(1-{3-[6-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-3-(2,2,2-trifluoro- ethyl)-1,3-dihydrobenzoimidazol-2-one; [3~(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-2-oxo-2,3-dihydro- benzoimidazol-1-yl]acetonitrile; 1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-3-(2-hydroxy- ethyl)-1,3-dihydro-benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(3-chloro-4-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yi)-6-chioro-1,3- dihydro-benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(3-chloro-4-methyl-phenyl)-4,5,6,7-tetrahydro- ) pyrazolo{4,3-c]pyridin-1-yi{]-2-hydroxy-propyl}-piperidin-4-yl)-3-methyl-1,3- dihydro-benzoimidazol-2-one;

. 1-Ethyl-3-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyi- phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-y|)- 1,3-dihydro-benzoimidazol-2-one;

1-(1-{2-Hydroxy-3-[5-methanesulfonyi-3-(4-trifluoromethyl-phenyf)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yi)-3-methyl- 1,3-dihydro-benzoimidazol-2-one; : 1-(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-3-(2-hydroxy- ’ ethyl)-1,3-dihydro-benzoimidazol-2-one; 3-(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl}-1,3-dihydro- imidazo[4,5-b]pyridin-2-one; [3-(1-{3-[5-Acetyi-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-2-oxo-2,3-dihydro- benzoimidazol-1-yl]-acetonitrile; 2-[3-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl!)-4,5,6,7-tetrahydro- pyrazolof4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl}-2-ox0-2,3-dihydro- benzoimidazol-1-yl]-acetamide; 1-(1-{3-[6-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-y{}-2-hydroxy-propyl}-piperidin-4-yl)-3-(2-oxo- tetrahydro-furan-3-yl)-1,3-dihydro-benzoimidazol-2-one; and 1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-3-(2-methoxy- ethyl)-1,3-dihydro-benzoimidazol-2-one.

69. A compound of claim 1, selected from: 1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-3-(2-oxo-butyl)-1,3- dihydro-benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyt)-4,5,6, 7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yi}-2-hydroxy-propyl}-piperidin-4-yl)-3-(2-diethylamino- ) ethyl)-1,3-dihydro-benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro-

. pyrazolof4,3-clpyridin-1-yl]-2-hyd roxy-propyl}-piperidin-4-yl )-3- cyclopropyimethyl-1,3-dihydro-benzoimidazol-2-one;

1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-3-(2-methyl-ally!)- 1,3-dihydro-benzoimidazol-2-one; } 1-(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazoloj4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-5-methyl-1,3- “ dihydro-benzoimidazol-2-one; 5-Chloro-3-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl- phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-1- methyl-1,3-dihydro-benzoimidazol-2-one; 6-Chloro-1-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl- phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yll-propyl}-piperidin-4-yi)- 1,3-dihydro-benzoimidazol-2-one; N-[4-(5-Acetyl-1-{2-hydroxy-3-[4-(2-ox0-2,3-dihydro-benzoimidazol-1-yl)- piperidin-1-yl]-propyl}-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)- phenyll-acetamide; [3-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl})-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-2-oxo-2,3-dihydro- benzoimidazol-1-yl]-acetic acid; 1-(1-{3-[5-Acetyl-3-(3-bromo-4-chloro-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro- benzoimidazol-2-one; 3-(1-{3-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-1-methyi-1,3- dihydro-imidazof4,5-b]pyridin-2-one; 3-(1-{2-Hydroxy-3-[6-methanesuifonyl-3-(4-trifluoromethyi-phenyl)- 4,5,6,7-tetrahydro-pyrazolo{4,3-c]pyridin-1-yi}-propyl}-piperidin-4-yl)-1-methyl- 1,3-dihydro-imidazo[4,5-b]pyridin-2-one; 1-(1-{3-[5-(1H-Imidazole-4-carbonyl)-3-(4-trifluoromethyl-phenyl)-4,5,6,7- ) tetrahydro-pyrazolof4,3-c]pyridin-1-yi}-propyl}-piperidin-4-yl)-3-methyi-1,3- dihydro-benzoimidazol-2-one;

. 1-{3-[4-(3-Methyl-2-0x0-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl}- propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo{4,3-c]pyridine- 5-carboxylic acid amide;

1-{3-[4-(3-Methyl-2-0x0-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl]- propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine- 5-carboxylic acid ethylamide; : 1-(1-{3-[5-(Isoxazole-5-carbonyl)-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-clpyridin-1-yl]-propyl}-piperidin-4-yl)-3-methyl-1,3- i: dihydro-benzoimidazol-2-one; 1-{3-[4-(3-Methyl-2-ox0-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yi}- propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine- 5-sulfonic acid (N-t-butoxycarbonyl)amide;

1-Methyl-3-(1-{3-[5-(5-methyl-isoxazole-3-carbonyl }-3-(4-trifluoromethyl- phenyl)-4,5,6,7-tetrahydro-pyrazolof4,3-c]pyridin-1-yi]-propyl}-piperidin-4-yl)- 1,3-dihydro-benzoimidazol-2-one;

3-(1-{3-[6-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propy}-piperidin-4-yl)-5-methoxy-1-

methyl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one;

3-(1-{3-[3-(4-Bromo-phenyl)-5-methanesuifonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-propy!}-piperidin-4-yl)-5-methoxy-1-methyl-1,3- dihydro-imidazo[4,5-b]pyridin-2-one;

5-Dimethylamino-3-(1-{3-[5-methanesulfonyl-3-(4-trifluoromethyl- :

phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yi)-1- methyl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one;

3-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulionyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yll-propy!}-piperidin-4-yl)-1-ethyl-5-methoxy-1,3- dihydro-imidazo[4,5-b]pyridin-2-one;

1-(1-{3-[5-Acetyl-3-(4-nitro-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1- yl]-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2-one;

1-(1-{3-[5-Acetyi-3-(4-nitro-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- clpyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-3-methyl-1,3-dihydro- . benzoimidazol-2-one;

3-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-

, c]pyridin-1-yl]-propyl}-piperidin-4-yl)-1-ethyl-5-methoxy-1,3-dihydro-imidazo[4,5- b]pyridin-2-one;

3-(1-{3-[5-Acetyl-3-(4-bromo-phenyl}-4,5,6,7-tetrahydro-pyrazolo[4,3- clpyridin-1-yl}-propyl}-piperidin-4-yl)-5-methoxy-1-methyl-1,3-dihydro- imidazo[4,5-b]pyridin-2-one; : 1-{3-[4-(3-Methyl-2-0x0-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl}- propyi}-3-(4-trifiuoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine- } 5-carboxylic acid benzyl ester; 5-Dimethylamino-3-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4- trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yi}-propyl}- piperidin-4-yl)-1-methyl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one;

1-{3-[4-(3-Methyl-2-o0x0-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl}- propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolof4,3-c]pyridine- 5-carbothioic acid methylamide;

3-(4-Bromo-phenyl)-1-{3-[4-(3-methyl-2-oxo-2,3-dihydro-benzoimidazol- 1-yl)-piperidin-1-yl}-propyi}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-

carboxylic acid phenylamide;

1-(1-{3-[5-Benzoyl-3-(4-bromo-phenyl}-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yi]-propyl}-piperidin-4-yl)-3-methyl-1,3-dihydro-benzoimidazol-2-one;

1-(1-{3-[3-(4-Bromo-phenyl)-5-methanesuifonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-3-methyl-1,3-dihydro-

benzoimidazol-2-one;

1-(1-{3-[6-Methanesulfonyl-3-(4-trifluoromethyl-phenyi)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yi]-propyl}-piperidin-4-yi)-1,3-dihydro- benzoimidazol-2-one;

3-(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-

pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-5-chloro-1-methyl-1,3- dihydro-benzoimidazol-2-one;

1-{3-[4-(6-Chloro-3-methyl-2-ox0-2,3-dihydro-benzoimidazol-1-yl)- piperidin-1-yl]-propyi}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro- , pyrazolo[4,3-c]pyridine-5-carboxylic acid amide;

1-(1-{3-[3-(4-Bromo-phenyl)-5-phenylmethanesuifonyl-4,5,6,7-

y tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-3-methyi-1,3- dihydro-benzoimidazol-2-one;

1-(1-{3-[6-Acetyl-3-(3,4-dichloro-phenyl)-4,5,6,7-tetrahydro-pyrazolof4,3- c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-3-methyi-1,3-dihydro- benzoimidazol-2-one; . 3-(4-Bromo-phenyl)-1-{3-[4-(3-methyl-2-ox0-2,3-dihydro-benzoimidazol- 1-yl)-piperidin-1-yl]-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5- ‘ carboxylic acid amide; 3-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- clpyridin-1-yl}-propyl}-piperidin-4-yl)-5-chloro-1-methyl-1,3-dihydro- benzoimidazol-2-one; 3-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-5-chloro-1-methyl-1,3- dihydro-benzoimidazol-2-one; 3-(4-Bromo-phenyl)-1-{3-[4-(6-chloro-3-methyl-2-ox0-2,3-dihydro- benzoimidazol-1-yl)-piperidin-1-yl}-propyl}-1,4,6,7-tetrahydro-pyrazolo(4,3- c]pyridine-5-carboxylic acid amide; 3-(1-{3-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-1,5-dimethyl-1,3- dihydro-benzoimidazol-2-one; and 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolof4,3- c]pyridin-1-yl}-propyl}-piperidin-4-yl)-3-methyl-1,3-dihydro-benzoimidazol-2-one.

70. A compound of claim 1, selected from: 3-(4-Bromo-phenyl)-1-{3-[4-(3-methyl-2-oxo0-2,3-dihydro-benzoimidazol- 1-yl)-piperidin-1-yl}-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-sulfonic acid t-butoxycarbonyl-amide; 1-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2- one; y 1-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yl}-propyl}-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2-one; v 3-~(4-Bromo-phenyl)-1-{3-[4-(2-ox0-2,3-dihydro-benzoimidazol-1-yl)- piperidin-1-yl}-propyi}-1,4,6,7-tetrahydro-pyrazolo{4,3-c]pyridine-5-sulfonic acid t-butoxycarbonyl-amide;

3-(4-Bromo-phenyl)-1-{3-[4-(2-ox0-2,3-dihydro-benzoimidazol-1-yl)- piperidin-1-yli}-propyi}-1,4,6,7-tetrahydro-pyrazolof4,3-c]pyridine-5-carboxylic acid amide; . (R)-5-Chloro-3-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl- phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yiJ-propyl}-piperidin-4-yl)-1- ‘ methyl-1,3-dihydro-benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(3,4-dichloro-phenyl!)-4,5,6, 7-tetrahydro-pyrazolo[4,3- clpyridin-1-yll-propyl}-piperidin-4-yl)-3-methyl-1,3-dihydro-benzoimidazol-2-one; 1-(1-{3-[3-(3,4-Dichloro-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-propyi}-piperidin-4-yl)-3-methyl-1,3-dihydro- benzoimidazol-2-one; 1-(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yi)-6-methoxy-1,3- dihydro-benzoimidazol-2-one; 3-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-1,3-dihydro- imidazo[4,5-b]pyridin-2-one; 3~(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolof4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-5-methoxy-1,3- dihydro-imidazo[4,5-b]pyridin-2-one; 1~{2-Hydroxy-3-[4-(2-oxo-1,2-dihydro-imidazo[4,5-b]pyridin-3-yi)- piperidin-1-yl]-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro- pyrazolof4,3-c]pyridine-5-carboxylic acid amide; 3-(4-Bromo-phenyl)-1-{2-hydroxy-3-[4-(2-oxo-1,2-dihydro-imidazo[4,5- b]pyridin-3-yl)-piperidin-1-yl]-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c)pyridine- 5-carboxylic acid amide; [3-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifl uoromethyl-phenyi)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yi]-propyi}-piperidin-4-yi)-2-oxo-2,3- . dihydro-imidazo[4,5-b]pyridin-1-yl]-acetonitrile; 3-(3,4-Dichloro-phenyl)-1-{3-[4-(2-ox0-2,3-dihydro-benzoimidazol-1-yl)-

. piperidin-1-yll-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid methylamide;

3-(1-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-1,3-dihydro-imidazo[4,5- blpyridin-2-one; . 3-(1-{3-[5-Acetyi-3-(4-trifluoromethyi-phenyi)-4,5,6, 7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-5-methoxy-1,3-dihydro- ‘ imidazo[4,5-b]pyridin-2-one; [3-(1-{3-[3-(4-Bromo-phenyl)-5-methanesulfonyl-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-2-oxo-2,3-dihydro- benzoimidazol-1-yl]-acetic acid ethyl ester; [3-(1 -{3-[5-Acetyl-3-(4-trifluoromethyl-phenyi)-4,5 ,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-2-oxo-2,3-dihydro- benzoimidazol-1-yl}-acetic acid ethyl ester; [3-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- clpyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-2-oxo-2,3-dihydro- benzoimidazol-1-yl]-acetic acid ethyl ester; 5-Chloro-3-(1-{3-[3-(3,4-dichloro-phenyl)-5-methanesulfonyi-4,5,6,7- tetrahydro-pyrazolo[4,3-c]pyridin-1-yi]-propyl}-piperidin-4-yi)-1-methyl-1,3- dihydro-benzoimidazol-2-one; (R)-1-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)- 4,5,6,7-tetrahydro-pyrazolo]4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-3-methyl- 1,3-dihydro-benzoimidazol-2-one; 1-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)- 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yi)-3-pyridin-4- ylmethyl-1,3-dihydro-benzoimidazol-2-one; (R)-5-Dimethylamino-3-(1-{2-hydroxy-3-[5-methanesulfonyl-3-(4- trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yi]-propyl}- piperidin-4-yl)-1-methyl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one; 3-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolof4,3- . clpyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-5-chloro-3H-benzooxazol-2-one; 3-(1-{3-[5-Acetyi-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-

. c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-4-methyl-3H-benzooxazol-2- one;

3-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- clpyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-2-oxo-2,3-dihydro- benzooxazole-6-carboxylic acid ethyl ester; p 3-(1-{3-[5-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- clpyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-ethanesulfonyl-3H- ‘ benzooxazol-2-one; 3-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl})-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-4-methyl-3H- benzooxazol-2-one;

3-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-2-oxo-2,3-dihydro- benzooxazole-6-carboxylic acid ethyl ester;

3-(1-{3-[6-Acetyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3- c]pyridin-1-yl}-2-hydroxy-propyl}-piperidin-4-yl)-6-methoxy-3H-benzooxazol-2- one;

3-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-ethanesulfonyl- 3H-benzooxazol-2-one; :

3-(1-{3-[5-Acetyl-3-(4-chioro-3-methyl-phenyl)-4,5,6,7-tetrahydro-

pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-6-methoxy-3H- benzooxazol-2-one;

3-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-3H-benzooxazol-2- one;

3-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro- pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-5-chloro-3H- benzooxazol-2-one;

3-(1-{2-Hydroxy-3-[6-methanesulfonyl-3-(4-trifluoromethyl-phenyl)- ) 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl}-propyl}-piperidin-4-yl)-3H- oxazoloj4,5-b]pyridin-2-one; . 1-[1-[3-(4-Benzooxazol-2-yl-piperidin-1-yl)-2-hydroxy-propyl}-3-(4- trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yi}-ethanone;

PCT/US01/25290 1-[1-{2-Hydroxy-3-[4-(6-methyl-benzooxazol-2-yl)-piperidin-1-yl]- propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin- 5-yl]-ethanone; 1-[1-{3-[4-Benzothiazol- 2-yloxy)-piperidin-1-yl]-2-hydroxy-propyl}-3-(4- trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]- ethanone; 1-[1-{2-Hydroxy-3-[4-(5-methyl-benzooxazol-2-yl)-piperidin-1-yl]- propyl}-3-(4-trifluoromethyl-phenyt)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin- 5-yl]-ethanone; 1-(3-(4-Chloro-phenyi)-1-{2-hydroxy-3-[4-(2-methoxy-phenyl)- : piperidin-1-yl]-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)- ethanone; 3-(4-Chloro-phenyl)-1-{2-hydroxy-3-[4-(2-methoxy-phenyl)-piperidin-1- yl]-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carbaldehyde; 1-[1-[3-(4-Benzo[b]thiophen-2-yl-piperidin-1-yl)-2-hydroxy-propyl]-3-(4- trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]- ethanone; and 1-[4-(6-Chloro-indol-1-yl)-piperidin-1-yl]-3-[5-methanesulfonyl-3-(4- trifluoromethyi-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propan-

2-0.

71. A pharmaceutical composition, comprising a compound of claim 1, 3, 5, 60, or 61 and a pharmaceutically acceptable carrier.

72. Use of a compound of claim 1, 3, 5, 60, or 61 in the manufacture of a medicament for treating a subject with a condition mediated by cathepsin S.

73. Use of a compound of claim 1, 3, 60 or 61 in the manufacture of a medicament for inhibiting cathepsin S activity in a subject.

74. Use of a compound of claim 1, 3, 60, or 61 in the manufacture of a medicament for treating an autoimmune disease, or inhibiting the progression of an autoimmune disease, in a subject. AMENDED SHEET

) PCT/US01/25290

75. Use of claim 74, wherein the autoimmune disease is selected from lupus, rheumatoid arthritis, and asthma.

76. Use of claim 74, wherein the autoimmune disease is asthma.

77. Use of a compound of claim 1, 3, 60, or 61 in the manufacture of a medicament for treating or inhibiting the progression of tissue transplant rejection in a subject, by administering to the subject a therapeutically effective amount of said medicament.

78. Use of claim 77, wherein said administration occurs after said subject has undergone a tissue transplant procedure.

79. Use of claim 77, wherein said administration to said subject occurs before or during a tissue transplant procedure.

80. A substance or composition for use in a method for treating a subject with a condition mediated by cathepsin S, said substance or composition comprising a compound of claim 1, 3, 5, 60, or 61, and said method comprising administering to the subject a therapeutically effective amount of said substance or composition.

81. A substance or composition for use in a method for inhibiting cathepsin S activity in a subject, said substance or composition comprising a compound of claim 1, 3, 60 or 61, and said method comprising administering to the subject a therapeutically effective amount of said substance or composition.

82. A substance or composition for use in a method for treating an autoimmune disease, or inhibiting the progression of an autoimmune disease, in a subject, said substance or composition comprising a compound of claim 1, 3, 60, or 61, and said method comprising administering to the subject a therapeutically effective amount of said substance or composition. AMENDED SHEET

) PCT/US01/25290

83. A substance or composition for use in a method of treatment of claim 82, wherein the autoimmune disease is selected from lupus, rheumatoid arthritis, and asthma.

84. A substance or composition for use in a method of treatment of claim 82, wherein the autoimmune disease is asthma.

85. A substance or composition for use in a method for treating or inhibiting the progression of tissue transplant rejection in a subject, said substance or composition comprising a compound of claim 1, 3, 60, or 61, and said method comprising administering to the subject a therapeutically effective amount of said substance or composition.

86. A substance or composition for use in a method of treatment of claim 85, wherein said administration occurs after said subject has undergone a tissue transplant procedure.

87. A substance or composition for use in a method of treatment of claim 85, wherein said administration to said subject occurs before or during a tissue transplant procedure.

88. A compound according to any one of claims 1 to 70, substantially and herein described and illustrated.

89. A composition according to claim 71, substantially and herein described and illustrated.

90. Use according to any one of claims 72 to 79, substantially and herein described and illustrated.

91. A substance or composition for use in a method of treatment according to any one of claims 80 to 87, substantially and herein described and illustrated. AMENDED SHEET

: PCT/US01/25290

92. A new compound, a new composition, a new use of a compound as claimed in any one of claims 1 to 70, or a substance or composition for a new use in a method of treatment, substantially as herein described. AMENDED SHEET