# Patent

## Title
Pyrazole-amides and -sulfonamides

## Abstract

Compounds, compositions and methods are provided which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltage-dependent sodium channels. More particularly, the invention provides pyrazole-amides and -sulfonamides, compositions and methods that are useful in the treatment of central or peripheral nervous system disorders, particularly pain and chronic pain by blocking sodium channels associated with the onset or recurrance of the indicated conditions. The compounds, compositions and methods of the present invention are of particular use for treating neuropathic or inflammatory pain by the inhibition of ion flux through a channel that includes a PN3 subunit.

## Background
CROSS-REFERENCES TO RELATED APPLICATIONS
This is a non-provisional filing of U.S. Provisional Patent Application No. 60/335,958, filed on Nov. 1, 2001, the disclosure of which is incorporated herein by reference in its entirety for all purposes.


FIELD OF THE INVENTION
This invention relates to the use of certain pyrazole amide and pyrazole sulfonamide compounds as sodium channel inhibitors and to the treatment of neuropathic pain by the inhibition of sodium channels. Additionally, this invention relates to novel pyrazole-based compounds that are useful as sodium channel inhibitors.
BACKGROUND OF THE INVENTION
Sodium channel-blocking agents have been reported to be effective in the treatment of various disease states, and have found particular use as local anesthetics and in the treatment of cardiac arrhythmias. It has also been reported that sodium channel-blocking agents may also be useful in the treatment of pain, including neuropathic pain; see, for example, Tanelian et al. Pain Forum. 4(2), 75–80 (1995). Preclinical evidence demonstrates that sodium channel-blocking agents selectively suppress abnormal ectopic neural firing in injured peripheral and central neurons, and it is via this mechanism that they are believed to be useful for relieving pain. Consistent with this hypothesis, it has been shown that sodium channels accumulate in the peripheral nerve at sites of axonal injury (Devor et al. J. Neurosci. 132: 1976 (1993)). Alterations in either the level of expression or distribution of sodium channels within an injured nerve, therefore, have a major influence on the pathophysiology of pain associated with this type of trauma.
An increasing body of evidence suggests that a voltage-dependent, tetrodotoxin (TTX)-resistant Na channel, PN3 (Nav1.8), may play a key role in sensitization in neuropathic pain states. Neuropathic pain can be described as pain associated with damage or permanent alteration of the peripheral or central nervous system. Clinical manifestations of neuropathic pain include a sensation of burning or electric shock, feelings of bodily distortion, allodynia and hyperalgesia.
PN3 is a member of a family of voltage-gated sodium channel alpha subunits. Names for this family include SCN, SCNA, and Navx.x. There are currently 10 known members falling into two subfamilies Nav1 (all but SCN6A) and Nav2 (SCN6A). The human channel was cloned by Rabert et al. (Pain 78(2): 107–114 (1998)). PN3 of other species has also been cloned. See, for example, Chen et al., Gene 202(1–2), 7–14 (1997); Souslova et al., Genomics 41(2), 201–209 (1997); Akopian et al., Nature 379(6562), 257–262 (1996).
PN3-null mutant mice exhibit a pronounced analgesia to mechanical noxious stimuli (Akopian A. N. et al., Nature Neurosci., 2(6): 541–548 (1999)). Selective “knock down” of PN3 protein in the rat dorsal root ganglion with specific antisense oligodeoxynucleotides prevents hyperalgesia and allodynia caused by either chronic nerve or tissue injury (Porreca et al., Proc. Nat. Acad. Sci., USA, 96: 7640–7644 (1999)). The biophysical properties of PN3 make it ideally suited to sustain repetitive firing of sensory neurons at the depolarized potentials characteristic of injured peripheral nerves. In both human and animal models of neuropathic pain, there is an increased expression of PN3 at the site of peripheral nerve injury (Clare et al., DDT 5: 506–519 (2000); Coward et al., Pain 85: 41–50 (2000)).
Patients with neuropathic pain do not respond to non-steroidal anti-inflammatory drugs (NSAIDS) and resistance or insensitivity to opiates is common. Most other treatments have limited efficacy or undesirable side effects. Mannion et al., Lancet, 353: 1959–1964 (1999) from the Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School wrote: “There is no treatment to prevent the development of neuropathic pain, nor to adequately, predictably and specifically control established neuropathic pain.”
PN3 is a promising molecular target for the treatment of neuropathic pain. One of the most attractive features of PN3 is the highly restricted and peripheral nature of its expression. Antisense studies have revealed no overt (particularly CNS-related) adverse effects, consistent with the localized, peripheral distribution of the channel (Novakovic et al., J. Neurosci., 18(6): 2174–2187 (1998)). Additionally, the high activation threshold of PN3 suggests that the channel may be relatively uninvolved in normal nociception. These properties of PN3 present the possibility that selective blockade of this particular voltage-gated sodium channel (VGSC) may offer effective pain relief without the significant side effect liability normally associated with more promiscuous VGSC blocking drugs. The compounds of the invention are potent inhibitors of PN3 channels.
Ohkawa et al. have described a class of cyclic ethers that are of use as sodium channel blockers (U.S. Pat. No. 6,172,085).
Currently, gabapentin is the market leading treatment for neuropathic pain. As with epilepsy, its mechanism of action for pain is unknown. It is a very safe, easy to use drug, which contributes to its sales. Efficacy for neuropathic pain is not impressive, as few as only 30% of patients respond to gabapentin treatment. Carbamazepine is also used to treat neuropathic pain.
In view of the limited number of agents presently available and the low levels of efficacy of the available agents, there is a pressing need for compounds that are potent, specific inhibitors of ion channels implicated in neuropathic pain. The present invention provides such compounds, methods of using them, and compositions that include the compounds.
SUMMARY OF THE INVENTION
It has now been discovered that pyrazole-amides and -sulfonamides are potent inhibitors of sodium channels. In the discussion that follows, the invention is exemplified by reference to the inhibition of sodium channels that are localized in the peripheral nervous system, and in particular those inhibitors that are selective inhibitors of PN3, and are useful for treating neuropathic pain through the inhibition of sodium ion flux through channels that include the PN3 subunit. The focus of the discussion is for clarity of illustration only.
The compounds and methods of the present invention are useful for treating diseases in which blocking or inhibiting one or more PN3 ion channel provides relief from the disease. Of particular interest is the use of the compounds and methods of the invention for treating pain and central or peripheral nervous system disorders. The present invention is of use for treating both inflammatory and neuropathic pain.
The present invention provides compounds which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltage-dependent sodium channels. More particularly, the invention provides compounds, compositions and methods that are useful in the treatment of central or peripheral nervous system disorders, particularly pain and chronic pain.
In one aspect, the present invention provides compounds according to Formula I:




or a pharmaceutically acceptable salt thereof. In Formula I, the symbols R1 and R3 are independently selected from hydrogen, (C1–C4)alkyl, (C3–C7)cycloalkyl, (C1–C4)haloalkyl, (C1–C6)heteroalkyl, amino, halo, cyano, nitro, hydroxy, aryl and heteroaryl. The symbol R2 represents hydrogen, (C1–C4)alkyl, (C1–C7)cycloalkyl, aryl, heteroaryl, aryl(C1–C4)alkyl, or heteroaryl(C1–C4)alkyl;

The symbol Y is a member selected from:




wherein X is a member selected from O, S and NR8. The symbol R8 represents hydrogen, cyano, nitro, alkyl, acyl, aryl or SO2R9. R9 is selected from alkyl, aryl, heteroaryl and heterocycloalkyl. The symbols R4 and R5 independently represent hydrogen, (C1–C10)alkyl, (C3–C7)cycloalkyl, (C1–C8)heteroalkyl, aryl, heteroaryl, aryl(C1–C4)alkyl, heteroaryl(C1–C4)alkyl and (C3–C8)heterocycloalkyl, with the proviso that if R4 is hydrogen, R5 is not hydrogen. R4 and R5 taken together with the nitrogen atom to which they are attached optionally form a 4- to 8-membered heterocycloalkyl ring. The symbol R6 represents hydrogen, (C1–C6)alkyl, aryl, heteroaryl, aryl(C1–C4)alkyl, heteroaryl(C1–C4)alkyl or (C1–C6)heteroalkyl. R7 is selected from (C1–C7)alkyl, (C3–C7)cycloalkyl, (C1–C7)alkenyl, (C1–C6)heteroalkyl, aryl, heteroaryl, aryl(C1–C4)alkyl, heteroaryl(C1–C4)alkyl, amino, alkoxy, (C3–C8)heterocycloalkyl and amino(C1–C5)alkyl, and and R6 and R7 together with the atoms to which they are attached optionally form a 4- to 8-membered heterocycloalkyl ring.

In another aspect, the present invention provides pharmaceutical compositions comprising a pharmaceutically acceptable excipient and a compound provided above.
In yet another aspect, the present invention provides a method for inhibiting ion flux through voltage dependent sodium channels, comprising contacting a cell containing the target ion channels with a compound that comprises a pyrazolyl moiety, such as the compounds of Formula I.
In still another aspect, the present invention provides a method for the treatment of diseases through inhibition of ion flux through voltage dependent sodium channels, the method comprising treating the host with an effective amount of a sodium channel inhibiting compound comprising a pyrazolyl moiety, such as a compound of Formula I.
Other objects, advantages and embodiments of the invention will be apparent from review of the detailed description that follows.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a table displaying structures of representative compounds of the invention.



DETAILED DESCRIPTION OF THE INVENTION AND THE PREFERRED EMBODIMENTS
Definitions:
The term “pain” refers to all categories of pain, including pain that is described in terms of stimulus or nerve response, e.g., somatic pain (normal nerve response to a noxious stimulus) and neuropathic pain (abnormal response of a injured or altered sensory pathway, often without clear noxious input); pain that is categorized temporally, e.g., chronic pain and acute pain; pain that is categorized in terms of its severity, e.g., mild, moderate, or severe; and pain that is a symptom or a result of a disease state or syndrome, e.g., inflammatory pain, cancer pain, AIDS pain, arthropathy, migraine, trigeminal neuralgia, cardiac ischaemia, and diabetic neuropathy (see, e.g., Harrison's Principles of Internal Medicine, pp. 93–98 (Wilson et al., eds., 12th ed. 1991); Williams et al., J. of Medicinal Chem. 42:1481–1485 (1999), herein each incorporated by reference in their entirety).
“Somatic” pain, as described above, refers to a normal nerve response to a noxious stimulus such as injury or illness, e.g., trauma, burn, infection, inflammation, or disease process such as cancer, and includes both cutaneous pain (e.g., skin, muscle or joint derived) and visceral pain (e.g., organ derived).
“Neuropathic” pain, as described above, refers to pain resulting from injury to or chronic changes in peripheral and/or central sensory pathways, where the pain often occurs or persists without an obvious noxious input.
“Biological medium,” as used herein refers to both in vitro and in vivo biological milieus. Exemplary in vitro “biological media” include, but are not limited to, cell culture, tissue culture, homogenates, plasma and blood. In vivo applications are generally performed in mammals, preferably humans.
“Compound of the invention,” as used herein refers to the compounds discussed herein, pharmaceutically acceptable salts and prodrugs of these compounds.
“Inhibiting” and “blocking,” are used interchangeably herein to refer to the partial or full blockade of a PN3 channel by a compound of the invention, which leads to a decrease in ion flux either into or out of a cell in which a PN3 channel is found.
Where substituent groups are specified by their conventional chemical formulae, written from left to right, they equally encompass the chemically identical substituents which would result from writing the structure from right to left, e.g., —CH2O— is intended to also recite —OCH2—; —NHS(O)2— is also intended to represent. —S(O)2HN—, etc.
The term “alkyl,” by itself or as part of another substituent, means, unless otherwise stated, a straight or branched chain, or cyclic hydrocarbon radical, or combination thereof, which may be fully saturated, mono- or polyunsaturated and can include di- and multivalent radicals, having the number of carbon atoms designated (i.e. C1–C10 means one to ten carbons). Examples of saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyl, (cyclohexyl)methyl, cyclopropylmethyl, homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. An unsaturated alkyl group is one having one or more double bonds or triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(1,4-pentadienyl), ethynyl, 1- and 3-propynyl, 3-butynyl, and the higher homologs and isomers. The term “alkyl,” unless otherwise noted, is also meant to include those derivatives of alkyl defined in more detail below, such as “heteroalkyl.” Alkyl groups, which are limited to hydrocarbon groups are termed “homoalkyl”.
The term “alkylene” by itself or as part of another substituent means a divalent radical derived from an alkane, as exemplified, but not limited, by —CH2CH2CH2CH2—, and further includes those groups described below as “heteroalkylene.” Typically, an alkyl (or alkylene) group will have from 1 to 24 carbon atoms, with those groups having 10 or fewer carbon atoms being preferred in the present invention. A “lower alkyl” or “lower alkylene” is a shorter chain alkyl or alkylene group, generally having eight or fewer carbon atoms.
The terms “alkoxy,” “alkylamino” and “alkylthio” (or thioalkoxy) are used in their conventional sense, and refer to those alkyl groups attached to the remainder of the molecule via an oxygen atom, an amino group, or a sulfur atom, respectively.
The term “amino” refers to —NRR′ in which R and R′ are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocycloalkyl.
The term “heteroalkyl,” by itself or in combination with another term, means, unless otherwise stated, a stable straight or branched chain, or cyclic hydrocarbon radical, or combinations thereof, consisting of the stated number of carbon atoms and at least one heteroatom selected from O, N, Si and S, and wherein the nitrogen and sulfur atoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized. The heteroatom(s) O, N and S and Si may be placed at any interior position of the heteroalkyl group or at the position at which the alkyl group is attached to the remainder of the molecule. Examples include, but are not limited to, —CH2—CH2—O—CH3, —CH2—CH2—NH—CH3, —CH2—CH2—N(CH3)—CH3, —CH2—S—CH2—CH3, —CH2—CH2, —S(O)—CH3, —CH2—CH2—S(O)2—CH3, —CH═CH—O—CH3, —Si(CH3)3, —CH2—CH═N—OCH3, and —CH═CH—N(CH3)—CH3. Up to two heteroatoms may be consecutive, such as, for example, —CH2—NH—OCH3 and —CH2—O-Si(CH3)3. Similarly, the term “heteroalkylene” by itself or as part of another substituent means a divalent radical derived from heteroalkyl, as exemplified, but not limited by, —CH2—CH2—S—CH2—CH2— and —CH2—S—CH2—CH2—NH—CH2—. For heteroalkylene groups, heteroatoms can also occupy either or both of the chain termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, and the like). Still further, for alkylene and heteroalkylene linking groups, no orientation of the linking group is implied by the direction in which the formula of the linking group is written. For example, the formula —C(O)2R′— represents both —C(O)2R′— and —R′C(O)2—.
In general, an “acyl” or “acyl substituent” is also selected from the group set forth above. As used herein, the term “acyl substituent” refers to groups attached to, and fulfilling the valence of a carbonyl carbon that is either directly or indirectly attached to the nucleus of the compounds of the present invention.
The terms “cycloalkyl” and “heterocycloalkyl”, by themselves or in combination with other terms, represent, unless otherwise stated, cyclic versions of “alkyl” and “heteroalkyl”, respectively. Additionally, for heterocycloalkyl, a heteroatom can occupy the position at which the heterocycle is attached to the remainder of the molecule. Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, and the like. Examples of heterocycloalkyl include, but are not limited to, 1-(1,2,5,6-tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1-piperazinyl, 2-piperazinyl, 1-pyrrolidine, 2-pyrrolidine, 3-pyrrolidine and the like.
The terms “halo” or “halogen,” by themselves or as part of another substituent, mean, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom. Additionally, terms such as “haloalkyl,” are meant to include monohaloalkyl and polyhaloalkyl. For example, the term “halo(C1–C4)alkyl” is meant to include, but not be limited to, trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, and the like.
The term “aryl” means, unless otherwise stated, a polyunsaturated, aromatic, hydrocarbon substituent which can be a single ring or multiple rings (preferably from 1 to 3 rings) which are fused together or linked covalently. The term “heteroaryl” refers to aryl groups (or rings) that contain from one to four heteroatoms selected from N, O, and S, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atom(s) are optionally quaternized. A heteroaryl group can be attached to the remainder of the molecule through a heteroatom. Non-limiting examples of aryl and heteroaryl groups include phenyl, 1-naphthyl, 2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 1-pyrazole, 3-pyrazolyl, 4-pyrazole, 5-pyrazole, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-benzothiazolyl, purinyl, 2-benzimidazolyl, 2-benzthiazole, 2-benzoxazole, 5-indolyl, 1-isoquinolyl, 5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3-quinolyl, and 6-quinolyl. Substituents for each of the above noted aryl and heteroaryl ring systems are selected from the group of acceptable substituents described below.
For brevity, the term “aryl” when used in combination with other terms (e.g., aryloxy, arylthioxy, arylalkyl) includes both aryl and heteroaryl rings as defined above. Thus, the term “arylalkyl” is meant to include those radicals in which an aryl group is attached to an alkyl group (e.g., benzyl, phenethyl, pyridylmethyl and the like) including those alkyl groups in which a carbon atom (e.g., a methylene group) has been replaced by, for example, an oxygen atom (e.g., phenoxymethyl, 2-pyridyloxymethyl, 3-(1-naphthyloxy)propyl, and the like).
Each of the above terms (e.g., “alkyl,” “heteroalkyl,” “aryl” and “heteroaryl”) include both substituted and unsubstituted forms of the indicated radical. Preferred substituents for each type of radical are provided below.
Substituents for the alkyl, and heteroalkyl radicals (including those groups often referred to as alkylene, alkenyl, heteroalkylene, heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl) are generally referred to as “alkyl substituents” and “heteroalkyl substituents,” respectively, and they can be one or more of a variety of groups selected from, but not limited to: -hydrogen, —OR′, ═O, ═NR′′′′, ═N—OR′, —NR′R′′, —SR′, -halogen, —SiR′R′′R′′′, —OC(O)R′, —C(O)R′, —CO2R′, —CONR′R′′, —OC(O)NR′R′′, —NR′C(O)R′′, —NR′′′—C(O)NR′R′′, —NR′C(O)2R′′, —NR′′′—C(NR′R′′)═NR′′′′, —NR′′′—C(NR′R′′)═NR′′′′, —S(O)R′, —S(O)2R′, —S(O)2NR′R′′, —NR′SO2R′′, —NR′′′ SO2NR′R′′—CN, —R′ and —NO2 in a number ranging from zero to (2m′+1), where m′ is the total number of carbon atoms in such radical. R′, R′′, R′′′ each preferably independently refer to hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, (e.g., aryl substituted with 1–3 halogens, substituted or unsubstituted alkyl, alkoxy or thioalkoxy groups), substituted or unsubstituted heteroaryl and substituted or unsubstituted arylalkyl. R′′′′ refers to hydrogen, alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted arylalkyl, —CN, —NO2 and —S(O)2R′. When a compound of the invention includes more than one R group, for example, each of the R groups is independently selected as are each R′, R′′, R′′′ and R′′′′ groups when more than one of these groups is present. When R′ and R′′ are attached to the same nitrogen atom, they can be combined with the nitrogen atom to form a 5-, 6-, or 7-membered ring. For example, —NR′R′′ is meant to include, but not be limited to, 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl and 4-morpholinyl. From the above discussion of substituents, one of skill in the art will understand that the term “alkyl” is meant to include groups including carbon atoms bound to groups other than hydrogen groups, such as haloalkyl (e.g., —CF3 and —CH2CF3) and acyl (e.g., —C(O)CH3, —C(O)CF3, —C(O)CH2OCH3, and the like).
Similar to the substituents described for the alkyl radical, the aryl substituents and heteroaryl substituents are generally referred to as “aryl substituents” and “heteroaryl substituents,” respectively and are varied and selected from, for example: hydrogen, —OR′, —C═NR′′′′NR′R′′, —NR′′′SO2NR′R′′, —NR′R′′, —SR′, -halogen, —SiR′R′′R′′′, —OC(O)R′, —C(O)R′, —CO2R′, —CONR′R′′, —OC(O)NR′R′′, —NR′′C(O)R′, —NR′′′—C(O)NR′R′′, —NR′′C(O)2R′, —NR′′′—C(N′R′′)═NR′′′′, —S(O)R′, —S(O)2R′, —S(O)2NR′R′′, —NR′′SO2R′, —CN and —NO2, —R′, —N3, —CH(Ph)2, fluoro(C1–C4)alkoxy, and fluoro(C1–C4)alkyl, in a number ranging from zero to the total number of open valences on the aromatic ring system; and where R′, R′′ and R′′′ each preferably independently refer to hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, (e.g., aryl substituted with 1–3 halogens, substituted or unsubstituted alkyl, alkoxy or thioalkoxy groups), substituted or unsubstituted heteroaryl and substituted or unsubstituted arylalkyl. R′′′′ refers to hydrogen, alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted arylalkyl, —CN, —NO2 and —S(O)2R′. When a compound of the invention includes more than one R group, for example, each of the R groups is independently selected as are each R′, R′′, R′′′ and R′′′′ groups when more than one of these groups is present. When R′ and R′′ are attached to the same nitrogen atom, they can be combined with the nitrogen atom to form a 5-, 6-, or 7-membered ring. For example, —NR′R′′ is meant to include, but not be limited to, 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl and 4-morpholinyl.
Two of the aryl substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -T-C(O)—(CRR′)q—U—, wherein T and U are independently —NR—, —O—, —CRR′— or a single bond, and q is an integer of from 0 to 3. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -A-(CH2)r—B—, wherein A and B are independently —CRR′—, —O—, —NR—, —S—, —S(O)—, —S(O)2—, —S(O)2NR′— or a single bond, and r is an integer of from 1 to 4. One of the single bonds of the new ring so formed may optionally be replaced with a double bond. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula —(CRR′)s—X—(CR′′R′′′)d—, where s and d are independently integers of from 0 to 3, and X is —O—, —NR′—, —S—, —S(O)—, —S(O)2—, or —S(O)2NR′—. The substituents R, R′, R′′and R′′′ are preferably independently selected from hydrogen or substituted or unsubstituted (C1–C6)alkyl.
As used herein, the term “heteroatom” includes oxygen (O), nitrogen (N), sulfur (S) and silicon (Si).
The symbol “R” is a general abbreviation that represents a substituent group that is selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl groups.
The symbol , whether utilized as a bond or displayed perpendicular to a bond indicates the point at which the displayed moiety is attached to the remainder of the molecule, solid support, etc.
The term “pharmaceutically acceptable salts” includes salts of the active compounds which are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein. When compounds of the present invention contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or a similar salt. When compounds of the present invention contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, methanesulfonic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galactunoric acids and the like (see, for example, Berge et al., “Pharmaceutical Salts”, Journal of Pharmaceutical Science, 1977, 66, 1–19). Certain specific compounds of the present invention contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts.
The neutral forms of the compounds are preferably regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner. The parent form of the compound differs from the various salt forms in certain physical properties, such as solubility in polar solvents, but otherwise the salts are equivalent to the parent form of the compound for the purposes of the present invention.
In addition to salt forms, the present invention provides compounds, which are in a prodrug form. Prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present invention. Additionally, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment. For example, prodrugs can be slowly converted to the compounds of the present invention when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent.
Certain compounds of the present invention can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms are equivalent to unsolvated forms and are encompassed within the scope of the present invention. Certain compounds of the present invention may exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by the present invention and are intended to be within the scope of the present invention.
Certain compounds of the present invention possess asymmetric carbon atoms (optical centers) or double bonds; the racemates, diastereomers, geometric isomers and individual isomers are encompassed within the scope of the present invention.
The compounds of the present invention may also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds may be radiolabeled with radioactive isotopes, such as for example tritium (3H), iodine-125 (125I) or carbon-14 (14C). All isotopic variations of the compounds of the present invention, whether radioactive or not, are intended to be encompassed within the scope of the present invention.
DESCRIPTION OF THE EMBODIMENTS
I. Inhibitors of Voltage-Dependent Sodium Channels
In one aspect, the present invention provides compounds having the formula:




or a pharmaceutically acceptable salt thereof. In Formula I, the symbols R1 and R3 independently represent hydrogen, (C1–C4)alkyl, (C3–C7)cycloalkyl, (C1–C4)haloalkyl, (C1–C6)heteroalkyl, amino, halo, cyano, nitro, hydroxy, aryl and heteroaryl. R2 is a moiety selected from hydrogen, (C1–C4)alkyl, (C1–C7)cycloalkyl, aryl, heteroaryl, aryl(C1–C4)alkyl, and heteroaryl(C1–C4)alkyl.

The symbol Y represents a member selected from:




wherein X is selected from O, S and NR8. The symbol R8 represents hydrogen, cyano, nitro, alkyl, acyl, aryl or SO2R9. R9 is selected from alkyl, aryl, heteroaryl and heterocycloalkyl.

R4 and R5 are independently selected from hydrogen, (C1–C10)alkyl, (C3–C7)cycloalkyl, (C1–C8)heteroalkyl, aryl, heteroaryl, aryl(C1–C4)alkyl, heteroaryl(C1–C4)alkyl and (C3–C8)heterocycloalkyl, with the proviso that if R4 is hydrogen, R5 is not hydrogen. R4 and R5 taken together with the nitrogen atom to which they are attached optionally form a 4- to 8-membered heterocycloalkyl ring.
The symbol R6 represents hydrogen, (C1–C6)alkyl, aryl, heteroaryl, aryl(C1–C4)alkyl, heteroaryl(C1–C4)alkyl or (C1–C6)heteroalkyl; and R7 is selected from (C1–C7)alkyl, (C3–C7)cycloalkyl, (C1–C7)alkenyl, (C1–C6)heteroalkyl, aryl, heteroaryl, aryl(C1–C4)alkyl, heteroaryl(C1–C4)alkyl, amino, alkoxy, (C3–C8)heterocycloalkyl and amino(C1–C5)alkyl. R6 and R7 together with the atoms to which they are attached optionally form a 4- to 8-membered heterocycloalkyl ring.
In a presently preferred embodiment Y is a member selected from:




in which R4, R5, R6, R7, and X are as described above.

In another exemplary embodiment, the invention provides a compound having a structure according to Formula II:




in which R1, R2, R3, and Y are as described above. In this embodiment, R1 and R3 are preferably each independently selected from hydrogen, (C1–C4)alkyl, (C3–C7)cycloalkyl, (C1–C4)haloalkyl and (C1–C5)heteroalkyl. R2 is preferably selected from aryl and heteroaryl; and X is preferably O.

In a further exemplary embodiment, R4 and R5 taken together with the nitrogen to which they are attached form a ring system such as that set forth below:




In another preferred embodiment, R3 is hydrogen; R4 is selected from (C1–C7)alkyl, (C3–C7)cycloalkyl, aryl, heteroaryl, aryl(C1–C4)alkyl and heteroaryl(C1–C4)alkyl; and R5 is selected from hydrogen or alkyl. Alternatively, R4 and R5 taken together with the nitrogen atom to which they are attached form a 4- to 8-membered heterocycloalkyl ring.
In yet a further preferred embodiment, the invention provides a compound in which R4 is a member selected from:




wherein n is an integer from 0 to 4; and k is an integer from 1 to 3. The symbols R2a and R2b are independently selected from hydrogen and (C1–C4)alkyl, and R2a and R2b taken together with the carbon atom to which they are attached optionally form a 3- to 8-membered carbocyclic or heterocycloalkyl ring.

The symbol M represents a moiety that is selected from NR10, O and S, wherein R10 is selected from hydrogen, (C1–C6)alkyl, (C1–C8)heteroalkyl aryl, heteroaryl and (C3–C8)cycloalkyl. A, B, D, E and G are independently moieties selected from N,N-oxide and CR11, with the proviso that at most three of A, B, D, E and G is N; and at most one of A, B, D, E and G is N-oxide.
R11 is a member selected from hydrogen, halo, amino, hydroxy, cyano, nitro, (C1–C4)alkyl, (C3–C7)cycloalkyl, (C1–C7)heteroalkyl, aryl, heteroaryl, (C3–C8)heterocycloalkyl, alkoxy, acyl, —C(NR12)R13, —SO2R15, —SO2NR13R14, —NR12SO15, —NR12SO2NR13R14, —NR12C(N—CN)NR13R14, —NR12C(N—SO2R15)NR13R14, —NR12C(N—COR15)NR13R14—CONR13R14, —NR12(C═CH—NO2)NR13R14, —NR12CONR13R14, —NR12CO—OR15, —OCONR13R14, and R11 and R2a taken together with the carbon atoms to which they are attached optionally form a 4- to 8-membered heterocycloalkyl group with the proviso that A is CR11.
R11a is selected from (C1–C6)alkyl, (C3–C7)cycloalkyl, (C3–C8)heterocycloalkyl, aryl and heteroaryl. The symbols R12, R13 and R14 independently represent hydrogen, (C1–C8)alkyl, (C3–C7)cycloalkyl, (C1–C8)heteroalkyl, aryl, heteroaryl, (C3–C8)heterocycloalkyl, aryl(C1–C4)alkyl, heteroaryl(C1–C4)alkyl, amino(C1–C4)alkyl and when R13 and R14 are attached to the same nitrogen atom, they are optionally combined to form a 5-, 6- or 7-membered ring.
R15 is selected from (C1–C8)alkyl, (C3–C8)cycloalkyl, (C1–C8)heteroalkyl, aryl, heteroaryl and (C3–C8)heterocycloalkyl
When R4 has a cyclic structure set forth above, R1 and R3 are preferably each members independently selected from hydrogen, (C1–C4)alkyl, (C3–C7)cycloalkyl, (C1–C4)haloalkyl and (C1–C5)heteroalkyl; and X is O. R2 is a preferably a member selected from aryl or heteroaryl.
In yet another preferred embodiment, the invention provides a compound in which R4 has a structure according to Formula III:




In Formula III, W is preferably selected from S, SO or SO2 or a single bond. SO2 is presently most preferred. The symbol R15 represents a moiety selected from (C1–C4)alkyl, (C1–C6)alkenyl, (C3–C7)cycloalkyl, aryl, heteroaryl, (C1–C8)heteroalkyl, NR16R17. R16 and R17 are independently selected from hydrogen, (C1–C4)alkyl, (C1–C7)cycloalkyl, (C1–C8)heteroalkyl, (C3–C8)heterocycloalkyl, aryl, heteroaryl, aryl(C1–C4)alkyl, heteroaryl(C1–C4)alkyl, amino(C1–C4)alkyl, with the proviso that when R15 is amino W is SO2;
The symbols T1, T2, T3 and T4 are each independently selected from hydrogen, halo, amino, cyano, nitro, (C1–C4)alkyl, (C3–C8)cycloalkyl, (C1–C4)haloalkyl, alkoxy, fluoro(C1–C4)alkoxy, (C1–C7)cycloalkyl, (C1–C7)heteroalkyl, aryl and heteroaryl. T1 and T2 taken together with the carbon atoms to which they are attached optionally form a 4- to 8-membered carbocyclic or heterocycloalkyl ring. T2 and T3 taken together with the carbon atoms to which they are attached optionally form a 4- to 8-membered carbocyclic or heterocycloalkyl ring. T3 and R15 taken together with the atoms to which they are attached optionally form a 4- to 8-membered carbocyclic or heterocycloalkyl ring. T4 and R15 taken together with the atoms to which they are attached optionally form a 4- to 8-membered carbocyclic or heterocycloalkyl ring.
In a preferred embodiment, R1 and R3 are each members independently selected from hydrogen, (C1–C4)alkyl, (C3–C7)cycloalkyl, (C1–C4)haloalkyl or (C1–C5)heteroalkyl; and X is O. R2 is preferably a member selected from aryl or heteroaryl.
Representative compounds of the invention are set forth in Example 24 and FIG. 1. Activities towards PN3 of selected compounds of the invention are provided in Table 1. The compounds numbers in Table 1 are cross-referenced to the compound numbers set forth in the Example and figures.










TABLE 1








Activity in Flux



Compound #
Assay



















20
+++



23
++



39
+++



114
+



154
+++



323
+++



411
+++



414
+++



444
++



449
+++



480
+++



1054
+++



1175
++







(+++ 0.1–4 μM;



++ 4.1–10 μM;



+ 10.1–30 μM)






Also within the scope of the present invention are compounds of the invention that are poly- or multi-valent species, including, for example, species such as dimers, trimers, tetramers and higher homologs of the compounds of the invention or reactive analogues thereof. The poly- and multi-valent species can be assembled from a single species or more than one species of the invention. For example, a dimeric construct can be “homodimeric” or “heterodimeric.” Moreover, poly- and multi-valent constructs in which a compound of the invention or a reactive analogue thereof, is attached to an oligomeric or polymeric framework (e.g., polylysine, dextran, hydroxyethyl starch and the like) are within the scope of the present invention. The framework is preferably polyfunctional (i.e. having an array of reactive sites for attaching compounds of the invention). Moreover, the framework can be derivatized with a single species of the invention or more than one species of the invention.
Moreover, the present invention includes compounds within the motif set forth in Formula I, which are functionalized to afford compounds having water-solubility that is enhanced relative to analogous compounds that are not similarly functionalized. Thus, any of the substituents set forth herein can be replaced with analogous radicals that have enhanced water solubility. For example, it is within the scope of the invention to, for example, replace a hydroxyl group with a diol, or an amine with a quaternary amine, hydroxy amine or similar more water-soluble moiety. In a preferred embodiment, additional water solubility is imparted by substitution at a site not essential for the ion channel activity of the compounds set forth herein with a moiety that enhances the water solubility of the parent compounds. Methods of enhancing the water-solubility of organic compounds are known in the art. Such methods include, but are not limited to, functionalizing an organic nucleus with a permanently charged moiety, e.g., quaternary ammonium, or a group that is charged at a physiologically relevant pH, e.g. carboxylic acid, amine. Other methods include, appending to the organic nucleus hydroxyl- or amine-containing groups, e.g. alcohols, polyols, polyethers, and the like. Representative examples include, but are not limited to, polylysine, polyethyleneimine, poly(ethyleneglycol) and poly(propyleneglycol). Suitable functionalization chemistries and strategies for these compounds are known in the art. See, for example, Dunn, R. L., et al., Eds. POLYMERIC DRUGS AND DRUG DELIVERY SYSTEMS, ACS Symposium Series Vol. 469, American Chemical Society, Washington, D.C. 1991.
Preparation of Sodium Channel Inhibitors
Compounds of the present invention may be prepared using starting materials readily available from commercial suppliers or known intermediates. Examples of starting materials available from commercial suppliers include, but are not limited to, 3-methyl-2-phenylpyrazole-4-carboxylic acid, 1-phenyl-5-propyl-1H-pyrazole-4-carboxylic acid, 1–4-chlorophenyl)-5-propyl-1H-pyrazole-4-carboxylic acid, 2-(4-chlorophenyl)-3-trifluoromethyl)pyrazole-4-carboxylic acid, 1–4-(4-chlorophenyl)-1,3-thiazole-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid, 1-(4-chlorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid, 5-fluoro-1-phenylpyrazole-4-carboxylic acid and 1-(4-fluorophenyl)-3,5-dimethyl-1H-pyrazole-4-carboxylic acid. Scheme 1 sets forth an exemplary synthetic scheme for the preparation of known intermediates used to prepare compounds of the invention.




In Scheme 1, anhydride a is contacted with allyl ether b to form adduct c. The pyrazole ring system d is formed by contacting adduct c with hydrazine or a hydrazine derivative. The trifluoromethyl group of the pyrazole ketone d is removed by treatment with base to afford the carboxylic acid e.
Numerous routes are available for elaborating the carboxylic acid moiety of intermediates of the invention. In an exemplary procedure, the pyrazole carboxylic acid (compound f; Scheme 2) is activated via conversion to the carboxylic acid chloride (compound g; Scheme 2) and made to react with an amine (e.g.; HNR4R5) in an organic solvent such as dichloromethane or tetrahydrofuran in the presence of a base such as triethylamine or pyridine to give an amide of Formula I where Y is:




and X is O (compound h; Scheme 2). One skilled in the art will recognize that an amide of the invention may be converted to a thioamido (i.e.; X is S) by treatment with Lawesson's reagent or other methods known in the literature.





Compounds of the present invention may also be prepared as shown in Schemes 3–6. In Scheme 3, the pyrazole amine (compound i) is made to react with a carboxylic acid chloride (e.g.; R7COCl) using similar conditions described above to give the amide of formula I where Y is




R6 is H and Z is O.





In Scheme 4, the pyrazole amine (i) may be made to react with an isocyanate in an organic solvent such as dichloromethane or tetrahydrofuran to give the urea (compound k) where Y is




R6 is H, Z is O and R7 is amino. Alternatively, the pyrazole amine (compound i) may be made to react with an isothiocyanate to give a thiourea (i.e.; Z is S).





In Scheme 5, the pyrazole amine (i) may be made to react with the oxazolidinone intermediate (compound 1) in an organic solvent such as tetrahydrofuran, acetonitrile or n-butanol, typically at elevated temperature (50–100° C.), to give the sulfenyl urea. Methods used to prepare oxazolidinone are described in the literature.




In Scheme 6, the pyrazole amine may be made to react with the phenoxy intermediate in an organic solvent such as tetrahydrofuran, acetonitrile or n-butanol, typically at elevated temperature (50–100° C.), to give the cyanoguanidine. Methods used to prepare the phenoxy intermediate are described in the literature.




II. Assays for Blockers of Sodium Ion Channels

PN3 monomers as well as PN3 alleles and polymorphic variants are subunits of sodium channels. The activity of a sodium channel comprising PN3 subunits can be assessed using a variety of in vitro and in vivo assays, e.g., measuring current, measuring membrane potential, measuring ion flux, e.g., sodium or guanidinium, measuring sodium concentration, measuring second messengers and transcription levels, and using e.g., voltage-sensitive dyes, radioactive tracers, and patch-clamp electrophysiology.
A number of experimental models in the rat are appropriate for assessing the efficacy of the compounds of the invention. For example, the tight ligation of spinal nerves described by Kim et al, Pain 50: 355–363 (1992) can be used to experimentally determine the effect of the compounds of the invention on a PN3 channel. For example, a sodium channel blockade in vitro assay can be used to determine the effectiveness of compounds of Formula I as sodium channel blockers in an in vitro model by the inhibition of compound action potential propagation in isolated nerve preparations (Kourtney and Stricharz, LOCAL ANESTHETICS, Springer-Verlag, New York, 1987). The mechanical allodynia in vivo assay is also of use in determining the efficacy of compounds of the invention (Kim and Chung Pain 50:355 (1992)). Mechanical sensitivity can be assessed using a procedure described by Chaplan et al., J. Neurosci. Methods 53: 55–63 (1994). Other assays of use are known to those of skill in the art. See, for example, Loughhead et al., U.S. Pat. No. 6,262,078.
Inhibitors of the PN3 sodium channels can be tested using biologically active recombinant PN3, or naturally occurring TTX-resistant sodium channels, or by using native cells, like cells from the nervous system expressing a PN3 channel. PN3 channels can be isolated, co-expressed or expressed in a cell, or expressed in a membrane derived from a cell. In such assays, PN3 is expressed alone to form a homomeric sodium channel or is co-expressed with a second subunit (e.g., another PN3 family member) so as to form a heteromeric sodium channel. Exemplary expression vectors include, but are not limited to, PN3-pCDNA3.1. The PN3 channel is stably expressed in mammalian expression systems.
Inhibition can be tested using one of the in vitro or in vivo assays described above. Samples or assays that are treated with a potential sodium channel inhibitor or activator are compared to control samples without the test compound, to examine the extent of inhibition. Control samples (untreated with activators or inhibitors) are assigned a relative sodium channel activity value of 100. Inhibition of channels comprising PN3 is achieved when the sodium channel activity value relative to the control is less than 70%, preferably less than 40% and still more preferably, less than 30%. Compounds that decrease the flux of ions will cause a detectable decrease in the ion current density by decreasing the probability of a channel comprising PN3 being open, by decreasing conductance through the channel, decreasing the number of channels, or decreasing the expression of channels.
Changes in ion flux may be assessed by determining changes in polarization (i.e., electrical potential) of the cell or membrane expressing the sodium channel. A preferred means to determine changes in cellular polarization is by measuring changes in current or voltage with the voltage-clamp and patch-clamp techniques, using the “cell-attached” mode, the “inside-out” mode, the “outside-out” mode, the “perforated cell” mode, the “one or two electrode” mode, or the “whole cell” mode (see, e.g., Ackerman et al., New Engl. J. Med. 336: 1575–1595 (1997)). Whole cell currents are conveniently determined using the standard methodology (see, e.g., Hamil et al., Pflugers. Archiv. 391: 85 (1981). Other known assays include: radiolabeled rubidium flux assays and fluorescence assays using voltage-sensitive dyes (see, e.g., Vestergarrd-Bogind et al., J. Membrane Biol. 88: 67–75 (1988); Daniel et al., J. Pharmacol. Meth. 25: 185–193 (1991); Holevinsky et al., J. Membrane Biology 137: 59–70 (1994)). Assays for compounds capable of inhibiting or increasing sodium flux through the channel proteins can be performed by application of the compounds to a bath solution in contact with and comprising cells having a channel of the present invention (see, e.g., Blatz et al., Nature 323: 718–720 (1986); Park, J. Physiol. 481: 555–570 (1994)). Generally, the compounds to be tested are present in the range from about 1 pM to about 100 mM, preferably from about 1 pM to about 1 μM.
The effects of the test compounds upon the function of the channels can be measured by changes in the electrical currents or ionic flux or by the consequences of changes in currents and flux. Changes in electrical current or ionic flux are measured by either increases or decreases in flux of ions such as sodium or guanidinium ions (see, e.g., Berger et al, U.S. Pat. No. 5,688,830). The cations can be measured in a variety of standard ways. They can be measured directly by concentration changes of the ions or indirectly by membrane potential or by radio-labeling of the ions. Consequences of the test compound on ion flux can be quite varied. Accordingly, any suitable physiological change can be used to assess the influence of a test compound on the channels of this invention. The effects of a test compound can be measured by a toxin-binding assay. When the functional consequences are determined using intact cells or animals, one can also measure a variety of effects such as transmitter release, hormone release, transcriptional changes to both known and uncharacterized genetic markers, changes in cell metabolism such as cell growth or pH changes, and changes in intracellular second messengers such as Ca2+, or cyclic nucleotides.
High throughput screening (HTS) is of use in identifying promising candidates of the invention. Physiologically, Na channels open and close on a ms timescale. To overcome the short time in which channels are open the HTS assay can be run in the presence of an agent that modifies the gating of the channel, such as deltamethrin. This agent modifies the gating of Na channels and keeps the pore open for extended periods of time. In addition, while Na channels are primarily selective for Na, other monovalent cations can permeate the channel.
The specificity and effect of the PN3 blocking agents of the invention can also be assayed against non-specific blockers of PN3, such as tetracaine, mexilitine, and flecainide.
III. Pharmaceutical Compositions of Sodium Channel Openers
In another aspect, the present invention provides pharmaceutical compositions comprising a pharmaceutically acceptable excipient and a pyrazole, such as a compound according to Formula I.
Formulation of the Compounds (Compositions)
The compounds of the present invention can be prepared and administered in a wide variety of oral, parenteral and topical dosage forms. Thus, the compounds of the present invention can be administered by injection, that is, intravenously, intramuscularly, intracutaneously, subcutaneously, intraduodenally, or intraperitoneally. Also, the compounds described herein can be administered by inhalation, for example, intranasally. Additionally, the compounds of the present invention can be administered transdermally. Accordingly, the present invention also provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier or excipient and a neutral compound of the invention or a pharmaceutically acceptable salt thereof.
For preparing pharmaceutical compositions from the compounds of the present invention, pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules. A solid carrier can be one or more substances, which may also act as diluents, flavoring agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material.
In powders, the carrier is a finely divided solid, which is in a mixture with the finely divided active component. In tablets, the active component is mixed with the carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired.
The powders and tablets preferably contain from 5% or 10% to 70% of the active compound. Suitable carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like. The term “preparation” is intended to include the formulation of the active compound with encapsulating material as a carrier providing a capsule in which the active component with or without other carriers, is surrounded by a carrier, which is thus in association with it. Similarly, cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid dosage forms suitable for oral administration.
For preparing suppositories, a low melting wax, such as a mixture of fatty acid glycerides or cocoa butter, is first melted and the active component is dispersed homogeneously therein, as by stirring. The molten homogeneous mixture is then poured into convenient sized molds, allowed to cool, and thereby to solidify.
Liquid form preparations include solutions, suspensions, and emulsions, for example, water or water/propylene glycol solutions. For parenteral injection, liquid preparations can be formulated in solution in aqueous polyethylene glycol solution.
Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavors, stabilizers, and thickening agents as desired. Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, and other well-known suspending agents.
Also included are solid form preparations, which are intended to be converted, shortly before use, to liquid form preparations for oral administration. Such liquid forms include solutions, suspensions, and emulsions. These preparations may contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.
The pharmaceutical preparation is preferably in unit dosage form. In such form the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packeted tablets, capsules, and powders in vials or ampoules. Also, the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form.
The quantity of active component in a unit dose preparation may be varied or adjusted from 0.1 mg to 10000 mg, more typically 1.0 mg to 1000 mg, most typically 10 mg to 500 mg, according to the particular application and the potency of the active component. The composition can, if desired, also contain other compatible therapeutic agents.
IV. Methods for Inhibiting Ion Flow in Voltage-Dependent Sodium Channels
In yet another aspect, the present invention provides methods for decreasing ion flow through voltage dependent sodium channels in a cell, comprising contacting a cell containing the target ion channels with a sodium channel-inhibiting amount of a pyrazole, such as a compound of Formula I.
The methods provided in this aspect of the invention are useful for the diagnosis of conditions that can be treated by inhibiting ion flux through voltage-dependent sodium channels, or for determining if a patient will be responsive to therapeutic agents, which act by inhibiting sodium channels.
V. Methods for Treating Conditions Mediated by Voltage-Dependent Sodium Channels
In still another aspect, the present invention provides a method for the treatment of a disorder or condition through inhibition of a voltage-dependent sodium channel. In this method, a subject in need of such treatment is administered an effective amount of a pyrazole compound, such as a compound according to Formula I. In a preferred embodiment, the compounds provided herein are used to treat a disorder or condition by inhibiting an ion channel of the voltage gated sodium channel family, e.g., PN3.
The compounds provided herein are useful as sodium channel inhibitors and find therapeutic utility via inhibition of voltage-dependent sodium channels in the treatment of diseases or conditions. The sodium channels that are typically inhibited are described herein as voltage-dependent sodium channels such as the PN3 sodium channels.
The compounds of the invention are particularly preferred for use in the treating, preventing or ameliorating pain or seizures. The method includes administering to a patient in need of such treatment, a therapeutically effective amount of a pyrazole compound, e.g., a compound of the invention or a pharmaceutically acceptable salt thereof.
The compounds, compositions and methods of the present invention are of particular use in treating pain, including both inflammatory and neuropathic pain. Exemplary forms of pain treated by a compound of the invention include, postoperative pain, osteoarthritis pain, pain associated with metastatic cancer, neuropathy secondary to metastatic inflammation, trigeminal neuralgia, glossopharangyl neuralgia, adiposis dolorosa, burn pain, acute herpetic and postherpetic neuralgia, diabetic neuropathy, causalgia, brachial plexus avulsion, occipital neuralgia, reflex sympathetic dystrophy, fibromyalgia, gout, phantom limb pain, burn pain, pain following stroke, thalamic lesions, radiculopathy, and other forms of neuralgic, neuropathic, and idiopathic pain syndromes.
Idiopathic pain is pain of unknown origin, for example, phantom limb pain. Neuropathic pain is generally caused by injury or infection of the peripheral sensory nerves. It includes, but is not limited to pain from peripheral nerve trauma, herpes virus infection, diabetes mellitus, causalgia, plexus avulsion, neuroma, limb amputation, and vasculitis. Neuropathic pain is also caused by nerve damage from chronic alcoholism, human immunodeficiency virus infection, hypothyroidism, uremia, or vitamin deficiencies.
Moreover, any sodium channel inhbitory substance possessed of satisfactory sodium channel inhibiting activity coupled with favorable intracranial transfer kinetics and metabolic stability is expected to show good efficacy in central nervous system (CNS) diseases and disorders such as central nervous system ischemia, central nervous system trauma (e.g. brain trauma, spinal cord injury, whiplash injury, etc.), epilepsy, seizures, neurodegenerative diseases (e.g. amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Huntington's chorea, Parkinson's disease, diabetic neuropathy, etc.), vascular dementia (e.g. multi-infarct dementia, Binswanger's disease, etc.), manic-depressive psychosis, depression, schizophrenia, chronic pain, trigeminal neuralgia, migraine, ataxia, bipolar disorder, spasticity, mood disorders, psychotic disorders, hearing and vision loss, age-related memory loss, learning deficiencies, anxiety and cerebral edema.
In treatment of the above conditions, the compounds utilized in the method of the invention are administered at the initial dosage of about 0.001 mg/kg to about 1000 mg/kg daily. A daily dose range of about 0.1 mg/kg to about 100 mg/kg is more typical. The dosages, however, may be varied depending upon the requirements of the patient, the severity of the condition being treated, and the compound being employed. Determination of the proper dosage for a particular situation is within the skill of the practitioner. Generally, treatment is initiated with smaller dosages, which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached. For convenience, the total daily dosage may be divided and administered in portions during the day, if desired.
EXAMPLES
The following examples are offered to illustrate, but not to limit the claimed invention.
In the examples below, unless otherwise stated, temperatures are given in degrees Celsius (° C.); operations were carried out at room or ambient temperature (typically a range of from about 18–25° C.; evaporation of solvent was carried out using a rotary evaporator under reduced pressure (typically, 4.5–30 mmHg) with a bath temperature of up to 60° C.; the course of reactions was typically followed by thin layer chromatography and reaction times are provided for illustration only; products exhibited satisfactory 1H-NMR and/or LCMS data; yields (when provided) are for illustration only; and the following conventional abbreviations are also used: mp (melting point), L (liter), mL (milliliters), mmol (millimoles), g (grams), mg (milligrams), min (minutes), LCMS (liquid chromatography-mass spectrometry) and h (hours), PS (polystyrene), DIEA (diisopropylethylamine).
Example 1
Preparation of 1-(3-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid




1,1,1,5,5,5-Hexafluoro-3-isobutoxymethylen-pentane-2,4-dione was prepared according to experimental procedures described in Synthesis 1990, 347–350.
3-Chlorophenylhydrazine (1.04 g, 7.29 mmol) was added to a solution of 1,1,1,5,5,5-hexafluoro-3-isobutoxymethylen-pentane-2,4-dione (2.13 g, 7.29 mmol) in acetonitrile (3 mL) at 0° C. The reaction mixture was warmed to room temperature, stirred for 16 h and concentrated under reduced pressure. The crude residue was treated with methanol (25 mL) and potassium hydroxide (2.00 g) and the reaction mixture refluxed for 18 h. The reaction mixture was concentrated under reduced pressure and the crude product was taken up in water, acidified with 6M hydrochloric acid and extracted with ethyl acetate (5×50 mL). The organic layers were collected, concentrated and crude product purified by column chromatography on silica gel to give 1-(3-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid. LCMS m/z=288.9(M−H)−.
Example 2
Preparation of 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid-pyridine-4-ylamide




1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl chloride (0.100 g, 0.324 mmol) was added to a solution of 4-aminopyridine (0.036 g, 0.387 mmol) and pyridine (0.078 mL, 0.969 mmol) in acetonitrile (10 mL). The reaction mixture was heated at 60° C. for 12 h, concentrated and the crude product was purified by column chromatography on silica gel to give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid pyridine-4-ylamide. LCMS m/z=366.9 (M+H)+.
Example 3
Preparation of 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-methane sulfonyl-phenyl)-amide




1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl chloride (0.250 g, 0.808 mmol) was added to a solution of 3-methylsulfonylaniline hydrochloride (0.184 g, 0.889 mmol) and triethylamine (0.563 mL, 4.04 mmol) in acetonitrile (20 mL). The reaction mixture heated at 60° C. for 12 h, concentrated and crude product purified by column chromatography on silica gel to give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-methane sulfonyl-phenyl)-amide. 1H-NMR (CD3OD, 300 MHz) δ 8.37 (s, 1H), 8.17 (s, 1H), 7.97 (d, 1H, J=8.5 Hz), 7.73 (d, 1H, J=8.0 Hz), 7.59–7.66 (m, 3H), 7.51 (d, 2H, J=8.8 Hz), 3.15 (s, 3H); LCMS m/z=443.9 (M+H)+.
Example 4
Preparation of 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid [2-(3-fluoro-phenyl)-ethyl]-amide




1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl chloride (0.100 g, 0.324 mmol) was added to a solution of 2-(3-fluoro-phenyl)ethylamine (0.051 mL, 0.389 mmol) and triethylamine (0.135 mL, 0.972 mmol) in acetonitrile (10 mL). The reaction mixture stirred for 1 hr at room temperature, concentrated and crude product purified by column chromatography on silica gel to give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid [2-(3-fluoro-phenyl)-ethyl]-amide. LCMS m/z=412.0 (M+H)+.
Example 5
Preparation of 1-(3-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 3-trifluoromethyl-benzylamide)




Benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) (0.083 g; 0.189 mmol) was added to a solution of 1-(3-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (0.050 g; 0.172 mmol), 3-trifluoromethyl benzylamine (0.030 g; 0.206 mmol) and triethylamine (0.072 mL; 0.516 mmol) in tetrahydrofuran (10 mL). The reaction mixture was stirred at room temperature for 4 h, concentrated and the crude product purified by column chromatography on silica gel to give 1-(3-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 3-trifluoromethyl-benzylamide. LCMS m/z=448.8 (M+H)+.
Example 6
Preparation of 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (2,4-difluoro-phenyl)-amide)




2-4-difluoro-phenylamine (0.004 g; 0.029 mL) was added to a suspension of 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl chloride (0.010 g; 0.032 mmol) and PS-DIEA (0.1 g) in acetonitrile (2 mL). The reaction mixture was shaken at room temperature for 12 h at which time PS-trisamine (0.1 g) was added to remove the excess acid chloride. After an additional 12 h of shaking, the reaction mixture was filtered and concentrated to give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (2,4-difluoro-phenyl)-amide. LCMS m/z=399.8 (M−H)−.

Example 7
Preparation of 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (2-fluoro-3-trifluoromethyl-phenyl)-amide




2-Fluoro-3-trifluoromethyl-phenylamine (0.007 g; 0.039 mmol) was added to a suspension of 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl chloride (0.010 g; 0.032 mmol) and PS-DIEA (0.1 g) in acetonitrile (2 mL). The reaction mixture was shaken at room temperature for 12 h at which time PS-TSCl (0.2 g) high loading was added to remove the excess amine. After an additional 12 h of shaking, the reaction mixture was filtered and concentrated to give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (2-fluoro-3-trifluoromethyl-phenyl)-amide. LCMS m/z=449.9 (M−H)−.

Example 8
Preparation of 1-(4-fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 3-trifluoromethyl-benzylamide




3-Trifluoromethyl benzylamine (0.014 mL, 0.100 mmole) was added to a suspension of 1-(4-fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (0.030 g; 0.109 mmol) and PS-Carbodiimide (0.2 g) in methylene chloride (2 mL). The reaction mixture was shaken at room temperature for 12 h at which time the reaction mixture was filtered and concentrated to give 1-(4-fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 3-trifluoromethyl-benzylamide. LCMS m/z=432.3 (M+H)+.
Example 9
Preparation of 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-ylamine




Bromine (4.70 mL, 100 mmol) was added to a solution of 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid amide (1.20 g, 4.15 mmol) in 3M NaOH (100 mL). The reaction mixture was heated at 100° C. for 1 hour, cooled to room temperature and extracted with EtOAc (3×50 mL). Organic layers were collected, concentrated and crude product purified by column chromatography to give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-ylamine (0.408 g, 38%).
Example 10
Preparation of 1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-3-(3-methanesulfonyl-phenyl)-urea




Triphosgene (0.042 g, 0.140 mmol) was added to a solution of 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-ylamine (0.100 g, 0.382 mmol) and Na2CO3 (0.405 g, 3.82 mmol) in CH2Cl2/H2O (50 mL, 1:1) and stirred at room temperature for 30 min. 3-Methanesulfonyl-phenylamine HCl (0.095 g, 0.458 mmol) was added to the reaction mixture, stirred at room temperature for 2 hrs, organic layer collected and aqueous layer extracted with EtOAc (3×25 mL). Organic layers were collected, concentrated and crude product purified by column chromatography to give 1-[1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-3-(3-methanesulfonyl-phenyl)-urea (0.040 g, 22%).
Example 11




Excess 3,4-dichlorophenylisocyanate was added to a solution of 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-ylamine (13.1 mg, 0.05 mmol) in THF (1 mL). The reaction was shaken overnight then the excess 3,4-dichlorophenylisocyanate was scavenged with PS-trisamine. The product (21.4 mg, 95%) was isolated by filtration and evaporation.
Example 12
Preparation of 3-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl]-amino}-benzenesulfonylfluoride




1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl chloride (3.00 g, 9.70 mmol) was added to 3-amino-benzenesulfonyl fluoride (1.87 g, 10.6 mmol) in CH2Cl2 (50 ml) containing pyridine (2.35 ml, 29.1 mmol). Reaction mixture stirred overnight at room temperature, concentrated under reduced pressure and crude product purified by column chromatography to give 3-{[1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl]-amino}-benzenesulfonyl fluoride (3.23 g, 74%).
Example 13
Preparation of 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-cyclopropylsulfamoyl-phenyl)-amide




Cyclopropyl amine (0.012 mL, 0.167 mmol) was added to 3-{[1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl]-amino}-benzenesulfonyl fluoride (0.025 g, 0.055 mmol) in CH2Cl2 (10 ml). Reaction mixture stirred overnight at room temperature, concentrated under reduced pressure and crude product purified by column chromatography to give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-cyclopropylsulfamoyl-phenyl)-amide (0.015 g, 55%).
Example 14
Preparation of 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-cyano-2-phenyl-isourea)-amide




Diphenyl N-cyanocarbonimidate (0.235 g, 0.984 mmol) was added to 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-amino-phenyl)-amide (0.250 g, 0.656 mmol) in CH3CN (10 mL) and heated at 80° C. overnight. Reaction mixture concentrated under reduced pressure and crude product purified by column chromatography to give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-cyano-2-phenyl-isourea)-amide (0.258 g, 75%).
Example 15
Preparation of 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid N′-methyl-cyanoguanidine




1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-cyano-2-phenyl-isourea)-amide (0.050 g, 0.095 mmol) was added to a solution of methyl amine (10 mL, 20 mmol, 2M in THF) and stirred overnight. Reaction mixture concentrated under reduced pressure and crude product purified by column chromatography to give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid N′-methyl-cyanoguanidine (0.038 g, 88%).
Example 16
Preparation of 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-methylsulfone-2-phenyl-isourea)-amide.




Diphenyl N-methylsulfone-carbonimidate (0.573 g, 1.97 mmol) was added to 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-amino-phenyl)-amide (0.500 g, 1.31 mmol) in CH3CN (20 mL) and heated at 80° C. for 2 days. Reaction mixture concentrated under reduced pressure and crude product purified by column chromatography to give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-methylsulfone-2-phenyl-isourea)-amide (0.700 g, 92%).
Example 17
Preparation of 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid [3-(N′-methylsulfone-N′′-cyclopropyl-guanidino)-phenyl]-amide




1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-methylsulfone-2-phenyl-isourea)-amide (0.025 g, 0.0432 mmol) was added to a solution of cyclopropyl amine (0.030 mL, 0.432 mmol) in THF (5 mL) and stirred overnight. Reaction mixture concentrated under reduced pressure and crude product purified by column chromatography to give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid [3-(N′-methylsulfone-N′′-cyclopropyl-guanidino)-phenyl]-amide (0.015 g, 65%)
Example 18
Preparation of 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-boronic acid-phenyl)-amide.




1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl chloride (0.100 g, 0.323 mmol) was added to 3-amino-boronic acid monohydrate (0.060 g, 0.388 mmol) in CH2Cl2 (5 ml) containing pyridine (0.078 ml, 0.970 mmol). Reaction mixture stirred 2 hours at 80° C., concentrated under reduced pressure and crude product purified by column chromatography to give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-boronic acid-phenyl)-amide. (0.130 g, 98%).
Example 19
Preparation of 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-thiazol-2-yl-phenyl)-amide




Dichlorobis(triphenylphosphine)palladium (II) (0.002 g, 0.00244 mmol) was added to a degassed (N2) mixture of 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-boronic acid-phenyl)-amide (0.100 g, 0.244 mmol), Na2CO3 (0.052 g, 0.488 mmol), and 2-Bromo-thiazole (0.048 g, 0.292 mmol) in H2O/toluene (1 mL/2 mL). Reaction mixture heated at 80° C. for 12 hours, cooled to room temperature and extracted with EtOAc (3×5 mL). Organic layers were collected, concentrated and crude product purified by column chromatography to give 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-thiazol-2-yl-phenyl)-amide (0.074 g, 67%).
Example 20
Preparation of 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-sulfamide-phenyl)-amide.




Sulfamide (0.010 g, 0.105 mmol) was added to 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-amino-phenyl)-amide (0.020 g, 0.00525 mmol) in 1,4-dioxane (2 mL) and heated at 120° C. overnight. Reaction mixture concentrated under reduced pressure and crude product purified by column chromatography to give 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-sulfamide-phenyl)-amide (0.013 g, 54%).
Example 21
Preparation of 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-dimethylsulfamide-phenyl)-amide.




Dimethylsulfamoyl chloride (0.010 g, 0.105 mmol) was added to 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-amino-phenyl)-amide (0.025 g, 0.0656 mmol) in CH3CN (2 mL) containing pyridine (0.016 mL, 0.196 mmol). Reaction mixture stirred overnight, concentrated under reduced pressure and crude product purified by column chromatography to give 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-dimethylsulfamide-phenyl)-amide (0.019 g, 59%).
Example 22
14C Guanidinium Ion Influx Binding Assay
PN3 stably expressed in a host cell line were maintained in DMEM with 5% fetal bovine serum and 300 μg/ml G-418. The cells were subcultured and grown to confluence in 96-well plates 24–48 h before each experiment. After the growth medium was removed, the cells were washed with warm buffer (25 mM Hepes-Tris, 135 mM choline chloride, 5.4 mM potassium chloride, 0.98 mM magnesium sulfate, 5.5 mM glucose, and 1 mg/ml BSA, pH 7.4) and incubated in buffer on a 36° C. slide warmer for approximately 10 minutes. Various concentrations of the test compounds or standard sodium channel blockers (10 μM) and then deltamethrine (10 μM) were added to each well. After the cells were exposed to deltamethrine for 5 minutes, 5 μM of 14C-guanidinium was added, incubated with the radioligand (30–60 min), washed with ice-cold buffer, and dissolved in 0.1N sodium hydroxide. The radioactivity and the protein concentration of each cell lysate were determined by liquid scintillation counting and the protein assay using Pierce BCA reagent.
Example 23
23.1 Mechanical Allodynia In Vivo Assay
This assay determines the effectiveness of compounds of Formula I in relieving one of the symptoms in an in vivo model of neuropathic pain produced by spinal nerve ligation, namely mechanical allodynia.
Tactile allodynia was induced in rats using the procedures described by Kim and Chung, Pain 50: 355–363 (1992). Briefly, the rats were anesthetized with 2–5% inhaled isoflurane and maintained by 1% isoflurane. Each animal was then placed in a prone position, a 3 cm lateral incision was made, and the left paraspinal muscles separated from the spinous process at the L4–S2 level. The L6 transverse process was then removed in order to visually identify the L4–L6 spinal nerves. The L5 and L6 spinal nerves were then individually isolated and tightly ligated with silk thread. The wound was then closed in layers by silk sutures. These procedures produced rats which developed a significant increase in sensitivity to mechanical stimuli that did not elicit a response in normal rats.
Mechanical sensitivity was assessed using a procedure described by Chaplan et al., J. Neurosci. Methods 53: 55–63 (1994). Briefly, a series of eight Von Frey filaments of varying rigidity strength were applied to the plantar surface of the hind paw ipsilaterial to the ligations with just enough force to bend the filament. The filaments were held in this position for no more than three seconds or until a positive allodynic response was displayed by the rat. A positive allodynic response consisted of lifting the affected paw followed immediately by licking or shaking of the paw. The order and frequency with which the individual filaments were applied were determined by using Dixon up-down method. Testing was initiated with the middle hair of the series with subsequent filaments being applied in consecutive fashion, either ascending or descending, depending on whether a negative or positive response, respectively, was obtained with the initial filament.
23.2 Thermal Hyperalgesia In Vivo Assay
This assay determines the effectiveness of compounds in relieving one of the symptoms of neuropathic pain produced by unilateral mononeuropathy, namely thermal hyperalgesia.
The rats having had surgery as described above were assessed for thermal hyperalgesia sensitivity at least 5–7 days post-surgery. Briefly, the rats were placed beneath inverted plexiglass cages upon an elevated glass platform and a radiant heat source beneath the glass was aimed at the plantar hindpaw. The duration of time before the hindpaw was withdrawn from the floor was measured to the nearest tenth of a second. The cutoff time for the heat stimulus was 40 seconds, and the light was calibrated such that this stimulus duration did not burn or blister the skin. Three latency measurements were taken for each hindpaw ipsilateral to the ligation in each test session, alternating left and right hindpaws, with greater than 1 minute intervals between tests.
23.3 Results
The results show that after oral administration the compounds of the invention produce efficacious anti-allodynic effects at doses less then or equal to 100 mg/kg. The results show that after IV administration the compounds of the invention produce efficacious anti-hyperalgesic effects at doses less than or equal to 30 mg/kg. Overall, the compounds of the present invention were found to be effective in reversing mechanical allodynia-like and thermal hyperalgesia-like symptoms.
Example 24
Example 24 sets forth representative compounds of the invention.












compound #
name
MZ

















1
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
423



carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide


2
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
380



carboxylic acid (pyridin-2-ylmethyl)-amide


3
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
380



carboxylic acid (pyridin-3-ylmethyl)-amide


4
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
380



carboxylic acid (pyridin-4-ylmethyl)-amide


5
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
467



carboxylic acid (2,4,6-trichloro-phenyl)-amide


6
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
447



carboxylic acid 3,4-dichloro-benzylamide


7
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
429



carboxylic acid [3-(4-methyl-piperazin-1-yl)-propyl]-



amide


8
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
461



carboxylic acid [2-(2,4-dichloro-phenyl)-ethyl]-amide


9
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
467



carboxylic acid [2-(3,4-dimethoxy-phenyl)-ethyl]-methyl-



amide


10
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
455



carboxylic acid (biphenyl-3-ylmethyl)-amide


11
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
370



carboxylic acid (5-methyl-isoxazol-3-yl)-amide


12
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
355



carboxylic acid (1H-pyrazol-3-yl)-amide


13
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
380



carboxylic acid (4-cyano-2H-pyrazol-3-yl)-amide


14
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
383



carboxylic acid (2-ethyl-2H-pyrazol-3-yl)-amide


15
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
371



carboxylic acid (5-hydroxy-1H-pyrazol-3-yl)-amide


16
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
356



carboxylic acid isoxazol-3-ylamide


17
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
431



carboxylic acid (5-phenyl-2H-pyrazol-3-yl)-amide


18
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
383



carboxylic acid (2,5-dimethyl-2H-pyrazol-3-yl)-amide


19
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
448



carboxylic acid (4-bromo-5-methyl-isoxazol-3-yl)-amide


20
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
445



carboxylic acid (2-methyl-5-phenyl-2H-pyrazol-3-yl)-



amide


21
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
447



carboxylic acid (5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-



3-yl)-amide


22
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
366



carboxylic acid pyridin-3-ylamide


23
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
366



carboxylic acid pyridin-4-ylamide


24
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
447



carboxylic acid 3-trifluoromethyl-benzylamide


25
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
447



carboxylic acid 4-trifluoromethyl-benzylamide


26
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
508



carboxylic acid [2-(3-chloro-4-fluoro-phenyl)-4-cyano-



2H-pyrazol-3-yl]-amide


27
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
458



carboxylic acid (5-bromo-6-methyl-pyridin-2-yl)-amide


28
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
453



carboxylic acid [2-(3,5-dimethoxy-phenyl)-ethyl]-amide


29
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-
393



(3,5-dimethoxy-phenyl)-ethyl]-amide


30
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
439



carboxylic acid 2,6-dimethoxy-benzylamide


31
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 2,6-
379



dimethoxy-benzylamide


32
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
432



carboxylic acid [2-(1H-indol-3-yl)-ethyl]-amide


33
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(1H-
372



indol-3-yl)-ethyl]-amide


34
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-
375



4-carbonyl]-amino}-propionic acid methyl ester


35
2-[(1-Phenyl-5-propyl-1H-pyrazole-4-carbonyl)-amino]-
315



propionic acid methyl ester


36
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-
417



4-carbonyl]-amino}-propionic acid methyl ester


37
4-Methyl-2-[(1-phenyl-5-propyl-1H-pyrazole-4-
357



carbonyl)-amino]-pentanoic acid methyl ester


38
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-
451



4-carbonyl]-amino}-3-phenyl-propionic acid methyl ester


39
3-Phenyl-2-[(1-phenyl-5-propyl-1H-pyrazole-4-
391



carbonyl)-amino]-propionic acid methyl ester


40
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
451



carboxylic acid (3-fluoro-5-



trifluoromethyl-phenyl)-amide


41
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (3-
391



fluoro-5-trifluoromethyl-phenyl)-amide


42
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole
490



4-carbonyl]-amino}-3-(1H-indol-3-yl)-propionic acid



methyl ester


43
3-(1H-Indol-3-yl)-2-[(1-phenyl-5-propyl-1H-pyrazole-4-
430



carbonyl)-amino]-propionic acid methyl ester


44
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
453



carboxylic acid [2-(3,4-dimethoxy-phenyl)-ethyl]-amide


45
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid
393



[2-(3,4-dimethoxy-phenyl)-ethyl]-amide


46
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
399



carboxylic acid (2-thiophen-2-yl-ethyl)-amide


47
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
339



thiophen-2-yl-ethyl)-amide


48
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
369



carboxylic acid (furan-2-ylmethyl)-amide


49
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (furan-
309



2-ylmethyl)-amide


50
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
394



carboxylic acid (2-pyridin-2-yl-ethyl)-amide


51
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
334



pyridin-2-yl-ethyl)-amide


52
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
448



carboxylic acid (1-benzyl-pyrrolidin-3-yl)-amide


53
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (1-
388



benzyl-pyrrolidin-3-yl)-amide


54
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
385



carboxylic acid (thiophen-2-ylmethyl)-amide


55
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid
325



(thiophen-2-ylmethyl)-amide


56
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
419



carboxylic acid (1H-benzoimidazol-2-ylmethyl)-amide


57
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (1H-
359



benzoimidazol-2-ylmethyl)-amide


58
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
400



carboxylic acid (1-ethyl-pyrrolidin-2-ylmethyl)-amide


59
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (1-
340



ethyl-pyrrolidin-2-ylmethyl)-amide


60
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
394



carboxylic acid (2-pyridin-3-yl-ethyl)-amide


61
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
334



pyridin-3-yl-ethyl)-amide


62
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
409



carboxylic acid (2-phenoxy-ethyl)-amide


63
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
349



phenoxy-ethyl)-amide


64
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
414



carboxylic acid [3-(2-oxo-pyrrolidin-1-yl)-propyl]-amide


65
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [3-(2-
354



oxo-pyrrolidin-1-yl)-propyl]-amide


66
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid
395



(biphenyl-3-ylmethyl)-amide


67
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
515



carboxylic acid 3,5-bis-trifluoromethyl-benzylamide


68
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid
455



3,5-bis-trifluoromethyl-benzylamide


69
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
424



carboxylic acid 4-nitro-benzylamide


70
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 4-nitro-
364



benzylamide


71
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
397



carboxylic acid (3-imidazol-1-yl-propyl)-amide


72
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (3-
337



imidazol-1-yl-propyl)-amide


73
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
373



carboxylic acid (tetrahydro-furan-2-ylmethyl)-amide


74
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid
313



(tetrahydro-furan-2-ylmethyl)-amide


75
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
385



carboxylic acid cyclohexylmethyl-amide


76
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid
325



cyclohexylmethyl-amide


77
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
345



carboxylic acid isobutyl-amide


78
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid
285



isobutyl-amide


79
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
405



carboxylic acid indan-1-ylamide


80
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid indan-
345



1-ylamide


81
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
357



carboxylic acid cyclopentylamide


82
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid
297



cyclopentylamide


83
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
402



carboxylic acid (2-morpholin-4-yl-ethyl)-amide


84
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
342



morpholin-4-yl-ethyl)-amide


85
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
439



carboxylic acid 3,5-dimethoxy-benzylamide


86
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 3,5-
379



dimethoxy-benzylamide


87
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid
363



(benzo[1,3]dioxol-5-ylmethyl)-amide


88
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 3-
387



trifluoromethyl-benzylamide


89
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
360



carboxylic acid (2-dimethylamino-ethyl)-amide


90
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
300



dimethylamino-ethyl)-amide


91
{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
389



carbonyl]-methyl-amino}-acetic acid ethyl ester


92
[Methyl-(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)-
329



amino]-acetic acid ethyl ester


93
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
343



pyrrolidin-1-yl-methanone


94
(1-Phenyl-5-propyl-1H-pyrazol-4-yl)-pyrrolidin-1-yl
283



methanone


95
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
405



(3,4-dihydro-1H-isoquinolin-2-yl)-methanone


96
(3,4-Dihydro-1H-isoquinolin-2-yl)-(1-phenyl-5-propyl-
345



1H-pyrazol-4-yl)-methanone


97
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
407



carboxylic acid benzyl-ethyl-amide


98
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid benzyl-
347



ethyl-amide


99
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
375



thiomorpholin-4-yl-methanone


100
(1-Phenyl-5-propyl-1H-pyrazol-4-yl)-thiomorpholin-4-yl-
315



methanone


101
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
414



carbonyl]-pyrrolidine-2-carboxylic acid dimethylamide


102
1-(1-Phenyl-5-propyl-1H-pyrazole-4-carbonyl)-
354



pyrrolidine-2-carboxylic acid dimethylamide


103
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
514



carboxylic acid (2-methoxy-benzyl)-(2-pyridin-2-yl-



ethyl)-amide


104
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
552



carboxylic acid (3,4-dichloro-benzyl)-(2-pyridin-2-yl-



ethyl)-amide


105
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
502



carboxylic acid (4-fluoro-benzyl)-(2-pyridin-2-yl-ethyl)-



amide


106
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
498



carboxylic acid (4-methyl-benzyl)-(2-pyridin-2-yl-ethyl)-



amide


107
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
552



carboxylic acid (3,4-dichloro-benzyl)-(2-pyridin-3-yl-



ethyl)-amide


108
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
543



carboxylic acid (3,4-dimethoxy-benzyl)-(1-phenyl-ethyl)-



amide


109
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
446



carboxylic acid (2-cyano-ethyl)-phenethyl-amide


110
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
552



carboxylic acid (3,4-dichloro-benzyl)-(2-pyridin-4-yl-



ethyl)-amide


111
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
440



carboxylic acid (5-chloro-benzooxazol-2-yl)-amide


112
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
434



carboxylic acid (3,5-dichloro-pyridin-2-yl)-amide


113
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
400



carboxylic acid (5-chloro-pyridin-2-yl)-amide


114
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
393



carboxylic acid phenethyl-amide


115
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
394



carboxylic acid (2-pyridin-4-yl-ethyl)-amide


116
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
468



carboxylic acid (3-chloro-5-trifluoromethyl-pyridin-2-yl)-



amide


117
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
464



carboxylic acid (3-diethylcarbamoyl-phenyl)-amide


118
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
525



carboxylic acid [4-(5-methyl-isoxazol-3-ylsulfamoyl)-



phenyl]-amide


119
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
399



carboxylic acid (2-chloro-phenyl)-amide


120
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
447



carboxylic acid (1-ethyl-2-methyl-1H-benzoimidazol-5-



yl)-amide


121
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
512



carboxylic acid [4-(6-methyl-benzothiazol-2-yl)-phenyl]-



amide


122
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
471



carboxylic acid (2-methoxy-biphenyl-4-yl)-amide


123
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
405



carboxylic acid (1H-indazol-6-yl)-amide


124
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
365



carboxylic acid phenylamide


125
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (3-
404



diethylcarbamoyl-phenyl)-amide


126
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [4-(5-
465



methyl-isoxazol-3-ylsulfamoyl)-phenyl]-amide


127
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
339



chloro-phenyl)-amide


128
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (1-
387



ethyl-2-methyl-1H-benzoimidazol-5-yl)-amide


129
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [4-(6-
452



methyl-benzothiazol-2-yl)-phenyl]-amide


130
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
411



methoxy-biphenyl-4-yl)-amide


131
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (1H-
345



indazol-6-yl)-amide


132
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid
305



phenylamide


133
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
430



acid (3-diethylcarbamoyl-phenyl)-amide


134
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
491



acid [4-(5-methyl-isoxazol-



3-ylsulfamoyl)-phenyl]-amide


135
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
365



acid (2-chloro-phenyl)-amide


136
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
413



acid (1-ethyl-2-methyl-1H-benzoimidazol-5-yl)-amide


137
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
478



acid [4-(6-methyl-benzothiazol-2-yl)-phenyl]-amide


138
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
437



acid (2-methoxy-biphenyl-4-yl)-amide


139
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
371



acid (1H-indazol-6-yl)-amide


140
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
331



acid phenylamide


141
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
379



carboxylic acid m-tolylamide


142
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
395



carboxylic acid (3-methoxy-phenyl)-amide


143
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
379



carboxylic acid benzylamide


144
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
393



carboxylic acid benzyl-methyl-amide


145
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
409



carboxylic acid 4-methoxy-benzylamide


146
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
424



carboxylic acid 3-nitro-benzylamide


147
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
393



carboxylic acid 3-methyl-benzylamide


148
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-
527



pyrazole-4-carbonyl]-amino}-3-phenyl-



propionic acid benzyl ester


149
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-
451



pyrazole-4-carbonyl]-amino}-3-phenyl-



propionic acid methyl ester


150
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-
493



pyrazole-4-carbonyl]-amino}-3-phenyl-



propionic acid tert-butyl ester


151
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
429



carboxylic acid (2-cyclohexyl-1-hydroxymethyl-ethyl)-



amide


152
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
390



carboxylic acid (3-cyano-phenyl)-amide


153
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
422



carboxylic acid 4-dimethylamino-benzylamide


154
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
443



carboxylic acid (3-methanesulfonyl-phenyl)-amide


155
4-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-
437



pyrazole-4-carbonyl]-amino}-benzoic acid ethyl ester


156
3-Phenyl-2-[(1-phenyl-5-propyl-1H-pyrazole-4-
467



carbonyl)-amino]-propionic acid benzyl ester


157
3-Phenyl-2-[(1-phenyl-5-propyl-1H-pyrazole-4-
391



carbonyl)-amino]-propionic acid methyl ester


158
3-Phenyl-2-[(1-phenyl-5-propyl-1H-pyrazole-4-
433



carbonyl)-amino]-propionic acid tert-butyl ester


159
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
369



cyclohexyl-1-hydroxymethyl-ethyl)-amide


160
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (3-
330



cyano-phenyl)-amide


161
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 4-
362



dimethylamino-benzylamide


162
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (3-
383



methanesulfonyl-phenyl)-amide


163
4-[(1-Phenyl-5-propyl-1H-pyrazole-4-carbonyl)-amino]-
377



benzoic acid ethyl ester


164
3-Phenyl-2-[(1-phenyl-5-trifluoromethyl-1H-pyrazole-4-
493



carbonyl)-amino]-propionic acid benzyl ester


165
3-Phenyl-2-[(1-phenyl-5-trifluoromethyl-1H-pyrazole-4-
417



carbonyl)-amino]-propionic acid methyl ester


166
3-Phenyl-2-[(1-phenyl-5-trifluoromethyl-1H-pyrazole-4-
459



carbonyl)-amino]-propionic acid tert-butyl ester


167
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
395



acid (2-cyclohexyl-1-hydroxymethyl-ethyl)-amide


168
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
356



acid (3-cyano-phenyl)-amide


169
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
388



acid 4-dimethylamino-benzylamide


170
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
409



acid (3-methanesulfonyl-phenyl)-amide


171
4-[(1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-
403



carbonyl)-amino]-benzoic acid ethyl ester


172
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
465



carboxylic acid 2-fluoro-5-trifluoromethyl-benzylamide


173
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
461



carboxylic acid [2-(3-trifluoromethyl-phenyl)-ethyl]-



amide


174
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-
473



pyrazol-4-yl]-(7-trifluoromethyl-3,4-dihydro-



2H-quinolin-1-yl)-methanone


175
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
463



carboxylic acid (3-trifluoromethyl-benzyloxy)-amide


176
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid
291



benzylamide


177
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid tert-
257



butylamide


178
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid
305



phenethyl-amide


179
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid
297



cyclohexylmethyl-amide


180
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid
269



cyclopentylamide


181
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid
367



(biphenyl-3-ylmethyl)-amide


182
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 3,5-
427



bis-trifluoromethyl-benzylamide


183
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 3-
359



trifluoromethyl-benzylamide


184
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid
335



(benzo[1,3]dioxol-5-ylmethyl)-amide


185
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 3,4-
359



dichloro-benzylamide


186
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
461



carboxylic acid methyl-(3-trifluoromethyl-benzyl)-amide


187
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
475



carboxylic acid ethyl-(3-trifluoromethyl-benzyl)-amide


188
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
437



carboxylic acid benzo[1,3]dioxol-5-ylmethyl-methyl-



amide


189
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
451



carboxylic acid benzo[1,3]dioxol-5-ylmethyl-ethyl-amide


190
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
399



carboxylic acid methyl-thiophen-2-ylmethyl-amide


191
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
413



carboxylic acid ethyl-thiophen-2-ylmethyl-amide


192
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
461



carboxylic acid methyl-(4-trifluoromethyl-benzyl)-amide


193
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
475



carboxylic acid ethyl-(4-trifluoromethyl-benzyl)-amide


194
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
494



carboxylic acid benzo[1,3]dioxol-5-ylmethyl-(2-



dimethylamino-ethyl)-amide


195
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
518



carboxylic acid (2-dimethylamino-ethyl)-(3-



trifluoromethyl-benzyl)-amide


196
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
390



carboxylic acid benzylamide


197
1-(6-Ethoxy-pyridazin-3-yl)-5-trifluoromethyl-1H-
391



pyrazole-4-carboxylic acid benzylamide


198
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4-
402



carboxylic acid benzylamide


199
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
390



carboxylic acid benzylamide


200
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
375



carboxylic acid benzylamide


201
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-
413



pyrazole-4-carboxylic acid benzylamide


202
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H-
413



pyrazole-4-carboxylic acid benzylamide


203
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-
345



carboxylic acid benzylamide


204
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
356



carboxylic acid tert-butylamide


205
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H-
347



pyrazole-4-carboxylic acid tert-butylamide


206
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4-
368



carboxylic acid tert-butylamide


207
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
356



carboxylic acid tert-butylamide


208
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
341



carboxylic acid tert-butylamide


209
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-
379



pyrazole-4-carboxylic acid tert-butylamide


210
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H-
379



pyrazole-4-carboxylic acid tert-butylamide


211
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-
311



carboxylic acid tert-butylamide


212
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
404



carboxylic acid phenethyl-amide


213
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H-
395



pyrazole-4-carboxylic acid phenethyl-amide


214
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4-
416



carboxylic acid phenethyl-amide


215
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
404



carboxylic acid phenethyl-amide


216
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
389



carboxylic acid phenethyl-amide


217
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-
427



pyrazole-4-carboxylic acid phenethyl-amide


218
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H-
427



pyrazole-4-carboxylic acid phenethyl-amide


219
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-
359



carboxylic acid phenethyl-amide


220
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
396



carboxylic acid cyclohexylmethyl-amide


221
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H-
387



pyrazole-4-carboxylic acid cyclohexylmethyl-amide


222
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4-
408



carboxylic acid cyclohexylmethyl-amide


223
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
396



carboxylic acid cyclohexylmethyl-amide


224
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
381



carboxylic acid cyclohexylmethyl-amide


225
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-
419



pyrazole-4-carboxylic acid cyclohexylmethyl-amide


226
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H-
419



pyrazole-4-carboxylic acid cyclohexylmethyl-amide


227
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-
351



carboxylic acid cyclohexylmethyl-amide


228
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
368



carboxylic acid cyclopentylamide


229
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H-
359



pyrazole-4-carboxylic acid cyclopentylamide


230
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4-
380



carboxylic acid cyclopentylamide


231
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
368



carboxylic acid cyclopentylamide


232
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
353



carboxylic acid cyclopentylamide


233
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-
391



pyrazole-4-carboxylic acid cyclopentylamide


234
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H-
391



pyrazole-4-carboxylic acid cyclopentylamide


235
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-
323



carboxylic acid cyclopentylamide


236
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
466



carboxylic acid (biphenyl-3-ylmethyl)-amide


237
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H-
457



pyrazole-4-carboxylic acid (biphenyl-3-ylmethyl)-amide


238
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4-
478



carboxylic acid (biphenyl-3-ylmethyl)-amide


239
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
466



carboxylic acid (biphenyl-3-ylmethyl)-amide


240
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
451



carboxylic acid (biphenyl-3-ylmethyl)-amide


241
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-
489



pyrazole-4-carboxylic acid (biphenyl-3-ylmethyl)-amide


242
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H-
489



pyrazole-4-carboxylic acid (biphenyl-3-ylmethyl)-amide


243
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-
421



carboxylic acid (biphenyl-3-ylmethyl)-amide


244
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
526



carboxylic acid 3,5-bis-trifluoromethyl-benzylamide


245
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H-
517



pyrazole-4-carboxylic acid 3,5-bis-trifluoromethyl-



benzylamide


246
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4-
538



carboxylic acid 3,5-bis-trifluoromethyl-benzylamide


247
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
526



carboxylic acid 3,5-bis-trifluoromethyl-benzylamide


248
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
511



carboxylic acid 3,5-bis-trifluoromethyl-benzylamide


249
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-
549



pyrazole-4-carboxylic acid 3,5-bis-trifluoromethyl-



benzylamide


250
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H-
549



pyrazole-4-carboxylic acid 3,5-bis-trifluoromethyl-



benzylamide


251
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
481



acid 3,5-bis-trifluoromethyl-benzylamide


252
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
458



carboxylic acid 3-trifluoromethyl-benzylamide


253
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H-
449



pyrazole-4-carboxylic acid



3-trifluoromethyl-benzylamide


254
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4-
470



carboxylic acid 3-trifluoromethyl-benzylamide


255
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
458



carboxylic acid 3-trifluoromethyl-benzylamide


256
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
443



carboxylic acid 3-trifluoromethyl-benzylamide


257
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-
481



pyrazole-4-carboxylic acid 3-



trifluoromethyl-benzylamide


258
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H-
481



pyrazole-4-carboxylic acid 3-



trifluoromethyl-benzylamide


259
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-
413



carboxylic acid 3-trifluoromethyl-benzylamide


260
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
434



carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide


261
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H-
425



pyrazole-4-carboxylic acid (benzo[1,3]dioxol-5-



ylmethyl)-amide


262
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4-
446



carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide


263
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
434



carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide


264
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
419



carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide


265
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-
457



pyrazole-4-carboxylic acid



(benzo[1,3]dioxol-5-ylmethyl)-amide


266
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H-
457



pyrazole-4-carboxylic acid (benzo[1,3]dioxol-5-



ylmethyl)-amide


267
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
389



acid (benzo[1,3]dioxol-5-ylmethyl)-amide


268
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
458



carboxylic acid 3,4-dichloro-benzylamide


269
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H-
449



pyrazole-4-carboxylic acid 3,4-dichloro-benzylamide


270
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4-
470



carboxylic acid 3,4-dichloro-benzylamide


271
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
458



carboxylic acid 3,4-dichloro-benzylamide


272
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
443



carboxylic acid 3,4-dichloro-benzylamide


273
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-
481



pyrazole-4-carboxylic acid 3,4-dichloro-benzylamide


274
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H-
481



pyrazole-4-carboxylic acid 3,4-dichloro-benzylamide


275
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
413



acid 3,4-dichloro-benzylamide


276
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
367



carboxylic acid pyrazin-2-ylamide


277
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
435



carboxylic acid (4,6-dichloro-pyrimidin-2-yl)-amide


278
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
383



carboxylic acid (3-fluoro-phenyl)-amide


279
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
410



carboxylic acid (3-nitro-phenyl)-amide


280
5,6-Dichloro-3-{[1-(4-chloro-phenyl)-5-
493



trifluoromethyl-1H-pyrazole-4-carbonyl]-



amino}-pyrazine-2-carboxylic acid methyl ester


281
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
385



carboxylic acid (2-cyclopentyl-ethyl)-amide


282
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid
243



benzylamide


283
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid tert-
209



butylamide


284
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid
257



phenethyl-amide


285
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid
249



cyclohexylmethyl-amide


286
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid
221



cyclopentylamide


287
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid
319



(biphenyl-3-ylmethyl)-amide


288
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid 3,5-bis-
379



trifluoromethyl-benzylamide


289
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid 3-
311



trifluoromethyl-benzylamide


290
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid
287



(benzo[1,3]dioxol-5-ylmethyl)-amide


291
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid 3,4-
311



dichloro-benzylamide


292
[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-
327



pyrazol-4-yl]-pyrrolidin-1-yl-methanone


293
[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-
410



pyrazol-4-yl]-(2-pyrrolidin-1-



ylmethyl-pyrrolidin-1-yl)-methanone


294
[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-
419



pyrazol-4-yl]-(4-pyridin-2-yl-piperazin-1-yl)-methanone


295
(4-Benzo[1,3]dioxol-5-ylmethyl-piperazin-
476



1-yl)-[1-(4-fluoro-phenyl)-5-trifluoromethyl-



1H-pyrazol-4-yl]-methanone


296
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
393



carboxylic acid 4-methoxy-benzylamide


297
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
423



carboxylic acid [2-(4-methoxy-phenoxy)-ethyl]-amide


298
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
449



carboxylic acid 3-fluoro-5-trifluoromethyl-benzylamide


299
[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-
356



pyrazol-4-yl]-(4-methyl-piperazin-1-yl)-methanone


300
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
403



carboxylic acid (1,2,3,4-tetrahydro-naphthalen-1-yl)-



amide


301
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
433



carboxylic acid [cyclopropyl-(4-methoxy-phenyl)-



methyl]-amide


302
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
447



carboxylic acid (2,3-dihydro-benzo[d]imidazo[2,1-



b]thiazol-6-yl)-amide


303
2-{[1-(4-Fluoro-phenyl)-5-trifluoromethyl-
511



1H-pyrazole-4-carbonyl]-amino}-3-phenyl-



propionic acid benzyl ester


304
4-{[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-
421



pyrazole-4-carbonyl]-amino}-benzoic acid ethyl ester


305
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
427



carboxylic acid (3-methanesulfonyl-phenyl)-amide


306
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
413



carboxylic acid (2-cyclohexyl-1-hydroxymethyl-ethyl)-



amide


307
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
369



carboxylic acid (thiophen-2-ylmethyl)-amide


308
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
353



carboxylic acid (furan-2-ylmethyl)-amide


309
1-[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-
384



pyrazole-4-carbonyl]-piperidine-3-carboxylic acid amide


310
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
389



carboxylic acid (2-phenyl-cyclopropyl)-amide


311
[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-
357



pyrazol-4-yl]-(3-hydroxy-piperidin-1-yl)-methanone


312
4-Phenyl-1-(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)-
398



piperidine-4-carbonitrile


313
1-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-4-
350



phenyl-piperidine-4-carbonitrile


314
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
457



carboxylic acid (3-methanesulfonyl-



phenyl)-methyl-amide


315
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
461



carboxylic acid [2-(3,4-dichloro-phenyl)-ethyl]-amide


316
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
303



carboxylic acid methylamide


317
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
317



carboxylic acid dimethylamide


318
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
407



carboxylic acid (3-acetyl-phenyl)-amide


319
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
487



carboxylic acid (5-ethanesulfonyl-2-methoxy-phenyl)-



amide


320
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
443



carboxylic acid (4-methanesulfonyl-phenyl)-amide


321
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
453



carboxylic acid (1,1-dioxo-1H-1lambda*6*-



benzo[b]thiophen-6-yl)-amide


322
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
411



carboxylic acid [2-(2-fluoro-phenyl)-ethyl]-amide


323
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
411



carboxylic acid [2-(3-fluoro-phenyl)-ethyl]-amide


324
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
427



carboxylic acid [2-(3-chloro-phenyl)-ethyl]-amide


325
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
427



carboxylic acid [2-(4-chloro-phenyl)-ethyl]-amide


326
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
461



carboxylic acid [2-(2,6-dichloro-phenyl)-ethyl]-amide


327
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
400



carboxylic acid (1-ethyl-pyrrolidin-2-ylmethyl)-amide


328
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
400



carboxylic acid (1-ethyl-pyrrolidin-2-ylmethyl)-amide


329
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic
323



acid [2-(3,4-dimethoxy-phenyl)-ethyl]-amide


330
(5-Chloro-1-methyl-1H-pyrazol-4-yl)-(4-methyl-
242



piperazin-1-yl)-methanone


331
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (1-
257



methyl-hexyl)-amide


332
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
243



(tetrahydro-furan-2-ylmethyl)-amide


333
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (2-
264



pyridin-2-yl-ethyl)-amide


334
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
427



acid [2-(3,4-dimethoxy-phenyl)-ethyl]-amide


335
[1-(4-Chloro-phenyl)-5-propyl-1H-pyrazol-4-yl]-(4-
346



methyl-piperazin-1-yl)-methanone


336
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
361



acid (1-methyl-hexyl)-amide


337
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
347



acid (tetrahydro-furan-2-ylmethyl)-amide


338
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
368



acid (2-pyridin-2-yl-ethyl)-amide


339
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid ethyl-
278



pyridin-4-ylmethyl-amide


340
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
291



benzyl-isopropyl-amide


341
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (1-
332



benzyl-pyrrolidin-3-yl)-methyl-amide


342
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (3-
272



diethylamino-propyl)-amide


343
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid 2,4-
309



dimethoxy-benzylamide


344
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
382



acid ethyl-pyridin-4-ylmethyl-amide


345
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
395



acid benzyl-isopropyl-amide


346
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
436



acid (1-benzyl-pyrrolidin-3-yl)-methyl-amide


347
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
376



acid (3-diethylamino-propyl)-amide


348
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
413



acid 2,4-dimethoxy-benzylamide


349
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
263



benzyl-methyl-amide


350
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (3,4-
271



difluoro-phenyl)-amide


351
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (3-
303



trifluoromethyl-phenyl)-amide


352
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
250



methyl-pyridin-2-yl-amide


353
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (3-
277



phenyl-propyl)-amide


354
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
367



acid benzyl-methyl-amide


355
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
375



acid (3,4-difluoro-phenyl)-amide


356
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
407



acid (3-trifluoromethyl-phenyl)-amide


357
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
354



acid methyl-pyridin-2-yl-amide


358
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
381



acid (3-phenyl-propyl)-amide


359
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (2-
264



pyridin-4-yl-ethyl)-amide


360
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
293



(benzo[1,3]dioxol-5-ylmethyl)-amide


361
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
263



phenethyl-amide


362
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (2-
253



ethyl-2H-pyrazol-3-yl)-amide


363
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic
331



acid [2-(3,4-dichloro-phenyl)-ethyl]-amide


364
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
368



acid (2-pyridin-4-yl-ethyl)-amide


365
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
397



acid (benzo[1,3]dioxol-5-ylmethyl)-amide


366
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
367



acid phenethyl-amide


367
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
357



acid (2-ethyl-2H-pyrazol-3-yl)-amide


368
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
435



acid [2-(3,4-dichloro-phenyl)-ethyl]-amide


369
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(3-
331



trifluoromethyl-phenyl)-ethyl]-amide


370
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (2-
269



thiophen-2-yl-ethyl)-amide


371
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(4-
297



chloro-phenyl)-ethyl]-amide


372
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid 3-
317



trifluoromethyl-benzylamide


373
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (3-
313



methanesulfonyl-phenyl)-amide


374
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
435



acid [2-(3-trifluoromethyl-phenyl)-ethyl]-amide


375
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
373



acid (2-thiophen-2-yl-ethyl)-amide


376
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
401



acid [2-(4-chloro-phenyl)-ethyl]-amide


377
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
421



acid 3-trifluoromethyl-benzylamide


378
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
417



acid (3-methanesulfonyl-phenyl)-amide


379
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
302



[2-(1H-indol-3-yl)-ethyl]-amide


380
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
281



[2-(3-fluoro-phenyl)-ethyl]-amide


381
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(2-
281



fluoro-phenyl)-ethyl]-amide


382
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (1-
270



ethyl-pyrrolidin-2-ylmethyl)-amide


383
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (1-
270



ethyl-pyrrolidin-2-ylmethyl)-amide


384
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
406



acid [2-(1H-indol-3-yl)-ethyl]-amide


385
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
385



acid [2-(3-fluoro-phenyl)-ethyl]-amide


386
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
385



acid [2-(2-fluoro-phenyl)-ethyl]-amide


387
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
374



acid (1-ethyl-pyrrolidin-2-ylmethyl)-amide


388
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
374



acid (1-ethyl-pyrrolidin-2-ylmethyl)-amide


389
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid 2,6-
309



dimethoxy-benzylamide


390
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(3-
297



chloro-phenyl)-ethyl]-amide


391
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
323



[2-(3,5-dimethoxy-phenyl)-ethyl]-amide


392
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (5-
270



chloro-pyridin-2-yl)-amide


393
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (2-
277



phenyl-propyl)-amide


394
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
413



acid 2,6-dimethoxy-benzylamide


395
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
401



acid [2-(3-chloro-phenyl)-ethyl]-amide


396
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
427



acid [2-(3,5-dimethoxy-phenyl)-ethyl]-amide


397
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
374



acid (5-chloro-pyridin-2-yl)-amide


398
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
381



acid (2-phenyl-propyl)-amide


399
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(4-
281



fluoro-phenyl)-ethyl]-amide


400
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
331



[2-(2,4-dichloro-phenyl)-ethyl]-amide


401
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
325



(biphenyl-3-ylmethyl)-amide


402
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
236



pyridin-4-ylamide


403
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (3-
375



benzenesulfonyl-phenyl)-amide


404
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
385



acid [2-(4-fluoro-phenyl)-ethyl]-amide


405
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
435



acid [2-(2,4-dichloro-phenyl)-ethyl]-amide


406
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
429



acid (biphenyl-3-ylmethyl)-amide


407
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
340



acid pyridin-4-ylamide


408
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
479



acid (3-benzenesulfonyl-phenyl)-amide


409
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
425



carboxylic acid [2-(3,4-dihydroxy-phenyl)-ethyl]-amide


410
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
381



carboxylic acid (3-hydroxy-phenyl)-amide


411
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
411



carboxylic acid [2-(4-fluoro-phenyl)-ethyl]-amide


412
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H-
495



pyrazole-4-carboxylic acid [2-(2,4-dichloro-phenyl)-



ethyl]-amide


413
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
461



carboxylic acid (2-fluoro-5-methanesulfonyl-phenyl)-



amide


414
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
427



carboxylic acid [2-(2-chloro-phenyl)-ethyl]-amide


415
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
409



carboxylic acid [2-(4-hydroxy-phenyl)-ethyl]-amide


416
1-(3-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
447



carboxylic acid 3-trifluoromethyl-benzylamide


417
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
454



carboxylic acid (3-methanesulfonyl-phenyl)-amide


418
1-(4-Amino-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
424



carboxylic acid (3-methanesulfonyl-phenyl)-amide


419
1-(2,5-Dichloro-phenyl)-1H-pyrazole-4-carboxylic acid
393



[2-(3-chloro-phenyl)-ethyl]-amide


420
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
438



carboxylic acid [2-(3-chloro-phenyl)-ethyl]-amide


421
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4-
450



carboxylic acid [2-(3-chloro-phenyl)-ethyl]-amide


422
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
438



carboxylic acid [2-(3-chloro-phenyl)-ethyl]-amide


423
1-(4-Amino-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
408



carboxylic acid [2-(3-chloro-phenyl)-ethyl]-amide


424
1-(4-Guanidino-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
466



carboxylic acid (3-methanesulfonyl-phenyl)-amide


425
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
393



acid [2-(2-chloro-phenyl)-ethyl]-amide


426
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
393



acid [2-(3-chloro-phenyl)-ethyl]-amide


427
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic
393



acid [2-(4-chloro-phenyl)-ethyl]-amide


428
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
427



[2-(2,4-dichloro-phenyl)-ethyl]-amide


429
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
427



[2-(3,4-dichloro-phenyl)-ethyl]-amide


430
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
427



[2-(2,6-dichloro-phenyl)-ethyl]-amide


431
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
377



[2-(2-fluoro-phenyl)-ethyl]-amide


432
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
377



[2-(3-fluoro-phenyl)-ethyl]-amide


433
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
377



[2-(4-fluoro-phenyl)-ethyl]-amide


434
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
427



[2-(3-trifluoromethyl-phenyl)-ethyl]-amide


435
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
387



[2-(4-ethyl-phenyl)-ethyl]-amide


436
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
419



[2-(3,5-dimethoxy-phenyl)-ethyl]-amide


437
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
419



[2-(3,4-dimethoxy-phenyl)-ethyl]-amide


438
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
365



(2-thiophen-2-yl-ethyl)-amide


439
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
363



4-fluoro-benzylamide


440
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
379



2-chloro-benzylamide


441
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
379



4-chloro-benzylamide


442
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
359



3-methyl-benzylamide


443
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
359



4-methyl-benzylamide


444
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
413



4-trifluoromethyl-benzylamide


445
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
431



3-fluoro-5-trifluoromethyl-benzylamide


446
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
409



carboxylic acid [2-(3-hydroxy-phenyl)-ethyl]-amide


447
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
375



[2-(3-hydroxy-phenyl)-ethyl]-amide


448
1-(3-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid (3-
375



methanesulfonyl-phenyl)-amide


449
1-(3-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid [2-(3-
359



chloro-phenyl)-ethyl]-amide


450
1-(3-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid [2-
393



(2,6-dichloro-phenyl)-ethyl]-amide


451
1-(4-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid (3-
375



methanesulfonyl-phenyl)-amide


452
1-(4-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid [2-(3-
359



chloro-phenyl)-ethyl]-amide


453
1-(4-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid [2-
393



(2,6-dichloro-phenyl)-ethyl]-amide


454
1-Benzyl-1H-pyrazole-4-carboxylic acid (3-
355



methanesulfonyl-phenyl)-amide


455
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(3-chloro-
339



phenyl)-ethyl]-amide


456
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(2,6-dichloro-phenyl)-
373



ethyl]-amide


457
1-p-Tolyl-1H-pyrazole-4-carboxylic acid (3-
355



methanesulfonyl-phenyl)-amide


458
1-p-Tolyl-1H-pyrazole-4-carboxylic acid [2-(3-chloro-
339



phenyl)-ethyl]-amide


459
1-p-Tolyl-1H-pyrazole-4-carboxylic acid [2-(2,6-dichloro-
373



phenyl)-ethyl]-amide


460
1-(2-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid (3-
375



methanesulfonyl-phenyl)-amide


461
1-(2-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid [2-(3-
359



chloro-phenyl)-ethyl]-amide


462
1-(2-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid [2-
393



(2,6-dichloro-phenyl)-ethyl]-amide


463
1-(3,4-Dichloro-phenyl)-1H-pyrazole-4-carboxylic acid
409



(3-methanesulfonyl-phenyl)-amide


464
1-(3,4-Dichloro-phenyl)-1H-pyrazole-4-carboxylic acid
393



[2-(3-chloro-phenyl)-ethyl]-amide


465
1-(3,4-Dichloro-phenyl)-1H-pyrazole-4-carboxylic acid
427



[2-(2,6-dichloro-phenyl)-ethyl]-amide


466
1-(4-Bromo-phenyl)-1H-pyrazole-4-carboxylic acid (3-
419



methanesulfonyl-phenyl)-amide


467
1-(4-Bromo-phenyl)-1H-pyrazole-4-carboxylic acid [2-(3-
403



chloro-phenyl)-ethyl]-amide


468
1-(4-Bromo-phenyl)-1H-pyrazole-4-carboxylic acid [2-
437



(2,6-dichloro-phenyl)-ethyl]-amide


469
1-(4-Fluoro-phenyl)-1H-pyrazole-4-carboxylic acid (3-
359



methanesulfonyl-phenyl)-amide


470
1-(4-Fluoro-phenyl)-1H-pyrazole-4-carboxylic acid [2-(3-
343



chloro-phenyl)-ethyl]-amide


471
1-(4-Fluoro-phenyl)-1H-pyrazole-4-carboxylic acid [2-
377



(2,6-dichloro-phenyl)-ethyl]-amide


472
1-(4-Methoxy-phenyl)-1H-pyrazole-4-carboxylic acid (3-
371



methanesulfonyl-phenyl)-amide


473
1-(4-Methoxy-phenyl)-1H-pyrazole-4-carboxylic acid [2-
355



(3-chloro-phenyl)-ethyl]-amide


474
1-(4-Methoxy-phenyl)-1H-pyrazole-4-carboxylic acid [2-
389



(2,6-dichloro-phenyl)-ethyl]-amide


475
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
391



[2-(3,4-dihydroxy-phenyl)-ethyl]-amide


476
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
375



[2-(4-hydroxy-phenyl)-ethyl]-amide


477
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
363



carboxylic acid benzylamide


478
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
377



carboxylic acid phenethyl-amide


479
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
411



carboxylic acid [2-(2-chloro-phenyl)-ethyl]-amide


480
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
411



carboxylic acid [2-(3-chloro-phenyl)-ethyl]-amide


481
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
411



carboxylic acid [2-(4-chloro-phenyl)-ethyl]-amide


482
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
445



carboxylic acid [2-(2,4-dichloro-phenyl)-ethyl]-amide


483
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
445



carboxylic acid [2-(3,4-dichloro-phenyl)-ethyl]-amide


484
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic
445



acid [2-(2,6-dichloro-phenyl)-ethyl]-amide


485
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
395



carboxylic acid [2-(2-fluoro-phenyl)-ethyl]-amide


486
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
395



carboxylic acid [2-(3-fluoro-phenyl)-ethyl]-amide


487
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
395



carboxylic acid [2-(4-fluoro-phenyl)-ethyl]-amide


488
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
445



carboxylic acid [2-(3-trifluoromethyl-phenyl)-ethyl]-



amide


489
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
433



carboxylic acid (2-trifluoromethyl-phenyl)-amide


490
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
401



carboxylic acid (2,4-difluoro-phenyl)-amide


491
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
407



carboxylic acid (4-isopropyl-phenyl)-amide


492
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
451



carboxylic acid (2-fluoro-5-trifluoromethyl-phenyl)-amide


493
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
405



carboxylic acid (2-isopropenyl-phenyl)-amide


494
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
393



carboxylic acid (4-ethyl-phenyl)-amide


495
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
451



carboxylic acid (2-fluoro-3-trifluoromethyl-phenyl)-amide


496
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
449



carboxylic acid (2-trifluoromethoxy-phenyl)-amide


497
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
393



carboxylic acid (2,5-dimethyl-phenyl)-amide


498
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
419



carboxylic acid (2,3,4-trifluoro-phenyl)-amide


499
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
383



carboxylic acid (2-fluoro-phenyl)-amide


500
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
421



carboxylic acid (4-tert-butyl-phenyl)-amide


501
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
467



carboxylic acid (2-chloro-5-trifluoromethyl-phenyl)-amide


502
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
433



carboxylic acid (3-trifluoromethyl-phenyl)-amide


503
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
379



carboxylic acid o-tolylamide


504
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
393



carboxylic acid (2,4-dimethyl-phenyl)-amide


505
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
421



carboxylic acid (2-tert-butyl-phenyl)-amide


506
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
393



carboxylic acid (2,6-dimethyl-phenyl)-amide


507
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
409



carboxylic acid (4-ethoxy-phenyl)-amide


508
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
400



carboxylic acid (2-chloro-pyridin-3-yl)-amide


509
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
433



carboxylic acid (2,4-dichloro-phenyl)-amide


510
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
441



carboxylic acid biphenyl-4-ylamide


511
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
413



carboxylic acid (5-chloro-2-methyl-phenyl)-amide


512
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
399



carboxylic acid (4-chloro-phenyl)-amide


513
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
390



carboxylic acid (4-cyano-phenyl)-amide


514
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-



carboxylic acid (3-benzenesulfonyl-phenyl)-amide


515
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
471



carboxylic acid (4-methoxy-biphenyl-3-yl)-amide


516
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
450



carboxylic acid (4-morpholin-4-yl-phenyl)-amide


517
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
433



carboxylic acid (4-trifluoromethyl-phenyl)-amide


518
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
450



carboxylic acid [4-(ethyl-isopropyl-amino)-phenyl]-amide


519
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
413



carboxylic acid (2-chloro-5-methyl-phenyl)-amide


520
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
448



carboxylic acid (2-piperidin-1-yl-phenyl)-amide


521
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
408



carboxylic acid (4-dimethylamino-phenyl)-amide


522
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
409



carboxylic acid (5-methoxy-2-methyl-phenyl)-amide


523
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
447



carboxylic acid (4-methyl-2-oxo-2H-chromen-7-yl)-amide


524
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
429



carboxylic acid (2-chloro-5-methoxy-phenyl)-amide


525
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
416



carboxylic acid quinolin-8-ylamide


526
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
430



carboxylic acid (2-pyrrol-1-yl-phenyl)-amide


527
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
480



carboxylic acid [2-(1H-indol-2-yl)-phenyl]-amide


528
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
404



carboxylic acid (3-cyanomethyl-phenyl)-amide


529
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
541



carboxylic acid [5-chloro-2-(4-chloro-phenylsulfanyl)-



phenyl]-amide


530
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
390



carboxylic acid (2-cyano-phenyl)-amide


531
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
409



carboxylic acid (4-methoxy-phenyl)-methyl-amide


532
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
395



carboxylic acid (4-methoxy-phenyl)-amide


533
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
434



carboxylic acid (5-trifluoromethyl-pyridin-2-yl)-amide


534
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
467



carboxylic acid (2-chloro-4-trifluoromethyl-phenyl)-amide


535
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
397



carboxylic acid (5-fluoro-2-methyl-phenyl)-amide


536
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
386



carboxylic acid (3-methyl-isothiazol-5-yl)-amide


537
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
372



carboxylic acid thiazol-2-ylamide


538
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
432



carboxylic acid (5-phenyl-oxazol-2-yl)-amide


539
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
407



carboxylic acid (1,1-dioxo-tetrahydro-1lambda*6*-



thiophen-3-yl)-amide


540
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
402



carboxylic acid (5-methylsulfanyl-1H-[1,2,4]triazol-3-yl)-



amide


541
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
356



carboxylic acid (1H-[1,2,4]triazol-3-yl)-amide


542
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
441



carboxylic acid (5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-



amide


543
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
370



carboxylic acid (3-methyl-isoxazol-5-yl)-amide


544
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
448



carboxylic acid (4-phenyl-thiazol-2-yl)-amide


545
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
422



carboxylic acid benzothiazol-2-ylamide


546
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
405



carboxylic acid (1H-benzoimidazol-2-yl)-amide


547
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
393



carboxylic acid 3-methoxy-benzylamide


548
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
393



carboxylic acid 2-methoxy-benzylamide


549
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
377



carboxylic acid 3-methyl-benzylamide


550
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
377



carboxylic acid 4-methyl-benzylamide


551
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
397



carboxylic acid 2-chloro-benzylamide


552
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
431



carboxylic acid 3,4-dichloro-benzylamide


553
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
423



carboxylic acid 2,4-dimethoxy-benzylamide


554
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
423



carboxylic acid 2,3-dimethoxy-benzylamide


555
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
397



carboxylic acid 4-chloro-benzylamide


556
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
369



carboxylic acid cyclohexylmethyl-amide


557
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
431



carboxylic acid 2,4-dichloro-benzylamide


558
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
489



carboxylic acid 3-iodo-benzylamide


559
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
381



carboxylic acid 2-fluoro-benzylamide


560
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
431



carboxylic acid 4-trifluoromethyl-benzylamide


561
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
357



carboxylic acid (tetrahydro-furan-2-ylmethyl)-amide


562
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
407



carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide


563
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
449



carboxylic acid 2-fluoro-5-trifluoromethyl-benzylamide


564
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
431



carboxylic acid 3-trifluoromethyl-benzylamide


565
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
499



carboxylic acid 3,5-bis-trifluoromethyl-benzylamide


566
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
423



carboxylic acid 2,6-dimethoxy-benzylamide


567
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
423



carboxylic acid 3,5-dimethoxy-benzylamide


568
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
377



carboxylic acid (1-phenyl-ethyl)-amide


569
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
364



carboxylic acid (pyridin-2-ylmethyl)-amide


570
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
455



carboxylic acid [2-(4-bromo-phenyl)-ethyl]-amide


571
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
407



carboxylic acid [2-(3-methoxy-phenyl)-ethyl]-amide


572
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
437



carboxylic acid [2-(3,5-dimethoxy-phenyl)-ethyl]-amide


573
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
437



carboxylic acid [2-(3,4-dimethoxy-phenyl)-ethyl]-amide


574
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
391



carboxylic acid (2-o-tolyl-ethyl)-amide


575
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
405



carboxylic acid [2-(3,4-dimethyl-phenyl)-ethyl]-amide


576
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
405



carboxylic acid [2-(2,4-dimethyl-phenyl)-ethyl]-amide


577
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
405



carboxylic acid (4-phenyl-butyl)-amide


578
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
393



carboxylic acid [2-(4-hydroxy-phenyl)-ethyl]-amide


579
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
383



carboxylic acid (2-chloro-phenyl)-amide


580
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
363



carboxylic acid o-tolylamide


581
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
363



carboxylic acid m-tolylamide


582
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
379



carboxylic acid (2-methoxy-phenyl)-amide


583
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
367



carboxylic acid (3-fluoro-phenyl)-amide


584
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
385



carboxylic acid (2,4-difluoro-phenyl)-amide


585
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
449



carboxylic acid (3-trifluoromethoxy-phenyl)-amide


586
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
399



(2-trifluoromethyl-phenyl)-amide


587
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
407



acid (2-trifluoromethyl-phenyl)-amide


588
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
373



trifluoromethyl-phenyl)-amide


589
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
366



(2-chloro-pyridin-3-yl)-amide


590
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
374



acid (2-chloro-pyridin-3-yl)-amide


591
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
340



chloro-pyridin-3-yl)-amide


592
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
373



(4-isopropyl-phenyl)-amide


593
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
381



acid (4-isopropyl-phenyl)-amide


594
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4-
347



isopropyl-phenyl)-amide


595
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
365



(4-chloro-phenyl)-amide


596
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
373



acid (4-chloro-phenyl)-amide


597
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4-
339



chloro-phenyl)-amide


598
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
359



(4-ethyl-phenyl)-amide


599
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
367



acid (4-ethyl-phenyl)-amide


600
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4-
333



ethyl-phenyl)-amide


601
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
356



(4-cyano-phenyl)-amide


602
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
364



acid (4-cyano-phenyl)-amide


603
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4-
330



cyano-phenyl)-amide


604
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
415



(2-trifluoromethoxy-phenyl)-amide


605
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
423



acid (2-trifluoromethoxy-phenyl)-amide


606
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
389



trifluoromethoxy-phenyl)-amide


607
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
416



(4-morpholin-4-yl-phenyl)-amide


608
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
424



acid (4-morpholin-4-yl-phenyl)-amide


609
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4-
390



morpholin-4-yl-phenyl)-amide


610
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
349



(2-fluoro-phenyl)-amide


611
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
357



acid (2-fluoro-phenyl)-amide


612
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
323



fluoro-phenyl)-amide


613
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
399



(4-trifluoromethyl-phenyl)-amide


614
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
407



acid (4-trifluoromethyl-phenyl)-amide


615
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4-
373



trifluoromethyl-phenyl)-amide


616
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
399



(3-trifluoromethyl-phenyl)-amide


617
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (3-
373



trifluoromethyl-phenyl)-amide


618
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
414



(2-piperidin-1-yl-phenyl)-amide


619
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
422



acid (2-piperidin-1-yl-phenyl)-amide


620
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-
388



piperidin-1-yl-phenyl)-amide


621
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
345



o-tolylamide


622
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
353



acid o-tolylamide


623
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid o-
319



tolylamide


624
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
382



quinolin-8-ylamide


625
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
390



acid quinolin-8-ylamide


626
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid
356



quinolin-8-ylamide


627
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
375



(4-ethoxy-phenyl)-amide


628
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
383



acid (4-ethoxy-phenyl)-amide


629
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4-
349



ethoxy-phenyl)-amide


630
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
437



[2-(4-bromo-phenyl)-ethyl]-amide


631
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
445



acid [2-(4-bromo-phenyl)-ethyl]-amide


632
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(4-
411



bromo-phenyl)-ethyl]-amide


633
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
387



[2-(3,4-dimethyl-phenyl)-ethyl]-amide


634
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
395



acid [2-(3,4-dimethyl-phenyl)-ethyl]-amide


635
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(3,4-
361



dimethyl-phenyl)-ethyl]-amide


636
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(3-
367



chloro-phenyl)-ethyl]-amide


637
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
389



[2-(2-methoxy-phenyl)-ethyl]-amide


638
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
397



acid [2-(2-methoxy-phenyl)-ethyl]-amide


639
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(2-
363



methoxy-phenyl)-ethyl]-amide


640
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(3-
351



fluoro-phenyl)-ethyl]-amide


641
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(3,4-
401



dichloro-phenyl)-ethyl]-amide


642
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(4-
367



chloro-phenyl)-ethyl]-amide


643
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
435



acid [2-(2,6-dichloro-phenyl)-ethyl]-amide


644
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(2,6-
401



dichloro-phenyl)-ethyl]-amide


645
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
389



[2-(3-methoxy-phenyl)-ethyl]-amide


646
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
397



acid [2-(3-methoxy-phenyl)-ethyl]-amide


647
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(3-
363



methoxy-phenyl)-ethyl]-amide


648
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
373



(2-o-tolyl-ethyl)-amide


649
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
381



acid (2-o-tolyl-ethyl)-amide


650
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-o-
347



tolyl-ethyl)-amide


651
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
375



(2-phenoxy-ethyl)-amide


652
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
383



acid (2-phenoxy-ethyl)-amide


653
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
387



(4-phenyl-butyl)-amide


654
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
395



acid (4-phenyl-butyl)-amide


655
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4-
361



phenyl-butyl)-amide


656
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
385



(1,2,3,4-tetrahydro-naphthalen-1-yl)-amide


657
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
393



acid (1,2,3,4-tetrahydro-naphthalen-1-yl)-amide


658
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid
359



(1,2,3,4-tetrahydro-naphthalen-1-yl)-amide


659
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
387



[2-(2,4-dimethyl-phenyl)-ethyl]-amide


660
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
395



acid [2-(2,4-dimethyl-phenyl)-ethyl]-amide


661
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(2,4-
361



dimethyl-phenyl)-ethyl]-amide


662
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
371



indan-1-ylamide


663
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic
379



acid indan-1-ylamide


664
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
471



carboxylic acid [2-(4-bromo-phenyl)-ethyl]-amide


665
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
423



carboxylic acid [2-(3-methoxy-phenyl)-ethyl]-amide


666
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
407



carboxylic acid (2-o-tolyl-ethyl)-amide


667
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
421



carboxylic acid (4-phenyl-butyl)-amide


668
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
421



carboxylic acid [2-(2,4-dimethyl-phenyl)-ethyl]-amide


669
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
421



carboxylic acid [2-(3,4-dimethyl-phenyl)-ethyl]-amide


670
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
423



carboxylic acid [2-(2-methoxy-phenyl)-ethyl]-amide


671
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
419



carboxylic acid (1,2,3,4-tetrahydro-naphthalen-1-yl)-



amide


672
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
449



carboxylic acid (2,4,6-triethyl-phenyl)-amide


673
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
407



carboxylic acid (2-ethyl-6-methyl-phenyl)-amide


674
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
407



carboxylic acid (2,4,6-trimethyl-phenyl)-amide


675
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
421



carboxylic acid (2,6-diethyl-phenyl)-amide


676
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
501



carboxylic acid (2,5-bis-trifluoromethyl-phenyl)-amide


677
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
449



carboxylic acid (2,6-diisopropyl-phenyl)-amide


678
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
421



carboxylic acid (2-isopropyl-6-methyl-phenyl)-amide


679
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
494



carboxylic acid (2,4,6-triethyl-3-nitro-phenyl)-amide


680
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
401



carboxylic acid (3,4-difluoro-phenyl)-amide


681
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
477



carboxylic acid (2,5-di-tert-butyl-phenyl)-amide


682
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
455



carboxylic acid (3-chloro-2,6-diethyl-phenyl)-amide


683
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
447



carboxylic acid (4-cyclohexyl-phenyl)-amide


684
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
521



carboxylic acid (2,5-dibromo-phenyl)-amide


685
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
407



carboxylic acid (2-isopropyl-phenyl)-amide


686
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 4-
325



chloro-benzylamide


687
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 2-
325



chloro-benzylamide


688
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 2-
309



fluoro-benzylamide


689
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 4-
309



fluoro-benzylamide


690
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (2-
311



chloro-phenyl)-amide


691
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (3-
311



chloro-phenyl)-amide


692
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (4-
311



chloro-phenyl)-amide


693
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
321



carboxylic acid benzylamide


694
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
335



carboxylic acid phenethyl-amide


695
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
365



carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide


696
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
355



carboxylic acid 4-chloro-benzylamide


697
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
355



carboxylic acid 2-chloro-benzylamide


698
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
339



carboxylic acid 2-fluoro-benzylamide


699
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
339



carboxylic acid 4-fluoro-benzylamide


700
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
341



carboxylic acid (2-chloro-phenyl)-amide


701
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
341



carboxylic acid (3-chloro-phenyl)-amide


702
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
341



carboxylic acid (4-chloro-phenyl)-amide


703
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid
277



phenylamide


704
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid
292



(pyridin-3-ylmethyl)-amide


705
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
307



carboxylic acid phenylamide


706
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
322



carboxylic acid (pyridin-3-ylmethyl)-amide


707
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
309



acid benzylamide


708
1-Benzyl-1H-pyrazole-4-carboxylic acid benzylamide
291


709
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
341



acid [2-(2-fluoro-phenyl)-ethyl]-amide


710
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(2-fluoro-
323



phenyl)-ethyl]-amide


711
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(2-fluoro-
323



phenyl)-ethyl]-amide


712
1-Benzyl-1H-pyrazole-4-carboxylic acid phenethyl-amide
305


713
1-Benzyl-1H-pyrazole-4-carboxylic acid phenethyl-amide
341


714
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(3-fluoro
323



phenyl)-ethyl]-amide


715
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
353



acid (benzo[1,3]dioxol-5-ylmethyl)-amide


716
1-Benzyl-1H-pyrazole-4-carboxylic acid
335



(benzo[1,3]dioxol-5-ylmethyl)-amide


717
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
341



acid [2-(4-fluoro-phenyl)-ethyl]-amide


718
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(4-fluoro-
323



phenyl)-ethyl]-amide


719
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
343



acid 4-chloro-benzylamide


720
1-Benzyl-1H-pyrazole-4-carboxylic acid 4-chloro-
325



benzylamide


721
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
357



acid [2-(3-chloro-phenyl)-ethyl]-amide


722
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
343



acid 2-chloro-benzylamide


723
1-Benzyl-1H-pyrazole-4-carboxylic acid 2-chloro-
325



benzylamide


724
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
357



acid [2-(4-chloro-phenyl)-ethyl]-amide


725
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(4-chloro-
339



phenyl)-ethyl]-amide


726
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
327



acid 2-fluoro-benzylamide


727
1-Benzyl-1H-pyrazole-4-carboxylic acid 2-fluoro-
309



benzylamide


728
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
353



acid [2-(2-methoxy-phenyl)-ethyl]-amide


729
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(2-methoxy-
335



phenyl)-ethyl]-amide


730
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
327



acid 4-fluoro-benzylamide


731
1-Benzyl-1H-pyrazole-4-carboxylic acid 4-fluoro-
309



benzylamide


732
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
353



acid [2-(3-methoxy-phenyl)-ethyl]-amide


733
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(3-methoxy-
335



phenyl)-ethyl]-amide


734
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
310



acid (pyridin-3-ylmethyl)-amide


735
1-Benzyl-1H-pyrazole-4-carboxylic acid (pyridin-3-
292



ylmethyl)-amide


736
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
391



acid [2-(3-trifluoromethyl-phenyl)-ethyl]-amide


737
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(3-
373



trifluoromethyl-phenyl)-ethyl]-amide


738
N-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
395



yl]-3-methoxy-benzamide


739
N-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
443



yl]-3-methanesulfonyl-benzamide


740
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (3-
355



methanesulfonyl-phenyl)-amide


741
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
385



carboxylic acid (3-methanesulfonyl-phenyl)-amide


742
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic
373



acid (3-methanesulfonyl-phenyl)-amide


743
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
433



carboxylic acid (5,6-dimethyl-1H-benzoimidazol-2-yl)-



amide


744
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
419



carboxylic acid (1-methyl-1H-benzoimidazol-2-yl)-amide


745
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
419



carboxylic acid (1H-benzoimidazol-2-yl)-methyl-amide


746
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (4-tert-
333



butyl-phenyl)-amide


747
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [2-
373



(2,4-dichloro-phenyl)-ethyl]-amide


748
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (4-
333



phenyl-butyl)-amide


749
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [2-
333



(2,4-dimethyl-phenyl)-ethyl]-amide


750
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [2-(2-
339



chloro-phenyl)-ethyl]-amide


751
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (4-
319



isopropyl-phenyl)-amide


752
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (2-o-
319



tolyl-ethyl)-amide


753
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [2-(4-
339



chloro-phenyl)-ethyl]-amide


754
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
403



carboxylic acid [2-(2,4-dichloro-phenyl)-ethyl]-amide


755
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
363



carboxylic acid (4-phenyl-butyl)-amide


756
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
363



carboxylic acid [2-(2,4-dimethyl-phenyl)-ethyl]-amide


757
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
369



carboxylic acid [2-(2-chloro-phenyl)-ethyl]-amide


758
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
349



carboxylic acid (4-isopropyl-phenyl)-amide


759
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
349



carboxylic acid (2-o-tolyl-ethyl)-amide


760
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
369



carboxylic acid [2-(4-chloro-phenyl)-ethyl]-amide


761
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (2-
342



pyrrol-1-yl-phenyl)-amide


762
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (2-
361



trifluoromethoxy-phenyl)-amide


763
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid
328



quinolin-8-ylamide


764
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
363



carboxylic acid (4-tert-butyl-phenyl)-amide


765
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
372



carboxylic acid (2-pyrrol-1-yl-phenyl)-amide


766
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
391



carboxylic acid (2-trifluoromethoxy-phenyl)-amide


767
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
358



carboxylic acid quinolin-8-ylamide


768
N-[5-(4-Chloro-phenyl)-2-methyl-2H-pyrazol-3-yl]-
311



benzamide


769
N-(2-Methyl-5-thiophen-2-yl-2H-pyrazol-3-yl)-benzamide
283


770
N-(5-Cyclopropyl-2-methyl-2H-pyrazol-3-yl)-benzamide
241


771
N-(2-Methyl-5-phenyl-2H-pyrazol-3-yl)-benzamide
277


772
N-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
365



yl]-benzamide


773
N-[5-(4-Chloro-phenyl)-2-methyl-2H-pyrazol-3-yl]-3-
329



fluoro-benzamide


774
N-(5-Cyclopropyl-2-methyl-2H-pyrazol-3-yl)-3-fluoro-
259



benzamide


775
N-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
383



yl]-3-fluoro-benzamide


776
N-[5-(4-Chloro-phenyl)-2-methyl-2H-pyrazol-3-yl]-2-
341



methoxy-benzamide


777
2-Methoxy-N-(2-methyl-5-thiophen-2-yl-2H-pyrazol-3-
313



yl)-benzamide


778
N-(5-Cyclopropyl-2-methyl-2H-pyrazol-3-yl)-2-methoxy-
271



benzamide


779
2-Methoxy-N-(2-methyl-5-phenyl-2H-pyrazol-3-yl)-
307



benzamide


780
N-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
395



yl]-2-methoxy-benzamide


781
N-[5-(4-Chloro-phenyl)-2-methyl-2H-pyrazol-3-yl]-3-
389



methanesulfonyl-benzamide


782
N-(5-Cyclopropyl-2-methyl-2H-pyrazol-3-yl)-3-
319



methanesulfonyl-benzamide


783
3-Methanesulfonyl-N-(2-methyl-5-phenyl-2H-pyrazol-3-
355



yl)-benzamide


784
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
458



yl]-3-(3-methanesulfonyl-phenyl)-urea


785
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
411



carbamic acid 2-methoxy-phenyl ester


786
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
487



carboxylic acid (1-methyl-5-trifluoromethyl-1H-



benzoimidazol-2-yl)-amide


787
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
437



carboxylic acid (5-fluoro-1-methyl-1H-benzoimidazol-2-



yl)-amide


788
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
433



carboxylic acid (1,6-dimethyl-1H-benzoimidazol-2-yl)-



amide


789
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
487



carboxylic acid (5,6-dichloro-1-methyl-1H-



benzoimidazol-2-yl)-amide


792
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
475



carboxylic acid [2-(2,4-dichloro-phenyl)-ethyl]-methyl-



amide


793
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
414



carboxylic acid (1-ethyl-pyrrolidin-2-ylmethyl)-methyl-



amide


794
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
425



carboxylic acid [2-(4-fluoro-phenyl)-ethyl]-methyl-amide


795
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
475



carboxylic acid [2-(2,6-dichloro-phenyl)-ethyl]-methyl-



amide


796
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
441



carboxylic acid [2-(2-chloro-phenyl)-ethyl]-methyl-amide


797
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
425



carboxylic acid [2-(2-fluoro-phenyl)-ethyl]-methyl-amide


798
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
425



carboxylic acid [2-(3-fluoro-phenyl)-ethyl]-methyl-amide


799
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
441



carboxylic acid [2-(3-chloro-phenyl)-ethyl]-methyl-amide


800
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
501



carboxylic acid (5-ethanesulfonyl-2-methoxy-phenyl)-



methyl-amide


801
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
441



carboxylic acid [2-(4-chloro-phenyl)-ethyl]-methyl-amide


802
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
475



carboxylic acid (2-fluoro-5-methanesulfonyl-phenyl)-



methyl-amide


803
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
463



carboxylic acid methyl-(3-trifluoromethoxy-phenyl)-



amide


804
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
437



carboxylic acid [2-(4-methoxy-phenyl)-ethyl]-methyl-



amide


805
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
483



carboxylic acid benzyl-(1-phenyl-ethyl)-amide


806
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
407



carboxylic acid methyl-phenethyl-amide


807
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
471



carboxylic acid bis-pyridin-3-ylmethyl-amide


808
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
471



carboxylic acid bis-pyridin-2-ylmethyl-amide


809
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
433



carboxylic acid (2-cyano-ethyl)-pyridin-3-ylmethyl-amide


810
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
435



(4-pyridin-2-yl-piperazin-1-yl)-methanone


811
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
435



carboxylic acid isopropyl-phenethyl-amide


812
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
483



carboxylic acid benzyl-(1-phenyl-ethyl)-amide


813
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
408



carboxylic acid ethyl-pyridin-4-ylmethyl-amide


814
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
341



(2,5-dihydro-pyrrol-1-yl)-methanone


815
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
361



thiazolidin-3-yl-methanone


816
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
439



carboxylic acid ethyl-(5-nitro-pyridin-2-yl)-amide


817
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
416



carboxylic acid quinolin-6-ylamide


818
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
466



carboxylic acid (4-nitro-benzyl)-propyl-amide


819
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
446



[3-(4-methoxy-phenyl)-pyrazol-l-yl]-methanone


820
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
426



(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone


821
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
414



yl]-3-(3-fluoro-phenyl)-thiourea


822
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
432



yl]-3-(2,5-difluoro-phenyl)-thiourea


823
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
448



yl]-3-(3,4-dichloro-phenyl)-urea


824
1-[1-(4-Chloro-cyclohexa-2,4-dienyl)-5-trifluoromethyl-
464



1H-pyrazol-4-yl]-3-(4-trifluoromethyl-phenyl)-thiourea


825
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
464



yl]-3-(2,4-dichloro-phenyl)-thiourea


826
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
411



carbamic acid 4-methoxy-phenyl ester


827
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
381



carbamic acid phenyl ester


828
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
361



carbamic acid isobutyl ester


829
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
464



yl]-3-(2,6-diisopropyl-phenyl)-urea


830
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
347



carbamic acid propyl ester


832
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
410



carboxylic acid (3-methanesulfonyl-phenyl)-amide


833
5-Trifluoromethyl-1-(5-trifluoromethyl-pyridin-2-yl)-1H-
482



pyrazole-4-carboxylic acid 4-trifluoromethyl-benzylamide


834
5-Trifluoromethyl-1-(5-trifluoromethyl-pyridin-2-yl)-1H-
446



pyrazole-4-carboxylic acid [2-(2-fluoro-phenyl)-ethyl]-



amide


835
5-Trifluoromethyl-1-(5-trifluoromethyl-pyridin-2-yl)-1H-
440



pyrazole-4-carboxylic acid (1H-benzoimidazol-2-yl)-



amide


836
5-Trifluoromethyl-1-(5-trifluoromethyl-pyridin-2-yl)-1H-
401



pyrazole-4-carboxylic acid pyridin-4-ylamide


837
5-Trifluoromethyl-1-(5-trifluoromethyl-pyridin-2-yl)-1H-
478



pyrazole-4-carboxylic acid (3-methanesulfonyl-phenyl)-



amide


838
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
448



4-carboxylic acid 4-trifluoromethyl-benzylamide


839
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
412



4-carboxylic acid [2-(2-fluoro-phenyl)-ethyl]-amide


840
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
406



4-carboxylic acid (1H-benzoimidazol-2-yl)-amide


841
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
367



4-carboxylic acid pyridin-4-ylamide


842
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
444



4-carboxylic acid (3-methanesulfonyl-phenyl)-amide


843
1-(6-Hydroxy-pyridazin-3-yl)-5-trifluoromethyl-1H-
427



pyrazole-4-carboxylic acid (3-methanesulfonyl-phenyl)-



amide


844
1-(6-Hydroxy-pyridazin-3-yl)-5-trifluoromethyl-1H-
389



pyrazole-4-carboxylic acid (1H-benzoimidazol-2-yl)-



amide


845
1-(6-Hydroxy-pyridazin-3-yl)-5-trifluoromethyl-1H-
395



pyrazole-4-carboxylic acid [2-(2-fluoro-phenyl)-ethyl]-



amide


846
1-(6-Hydroxy-pyridazin-3-yl)-5-trifluoromethyl-1H-
431



pyrazole-4-carboxylic acid 4-trifluoromethyl-benzylamide


847
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
408



carboxylic acid methyl-(2-pyridin-2-yl-ethyl)-amide


848
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
394



carboxylic acid methyl-pyridin-3-ylmethyl-amide


849
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
416



carboxylic acid quinolin-3-ylamide


850
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
533



carboxylic acid benzyl-(3-methanesulfonyl-phenyl)-amide


851
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
471



carboxylic acid ethyl-(3-methanesulfonyl-phenyl)-amide


852
[[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
529



carbonyl]-(3-methanesulfonyl-phenyl)-amino]-acetic acid



ethyl ester


853
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
482



carboxylic acid cyanomethyl-(3-methanesulfonyl-phenyl)-



amide


854
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
583



carboxylic acid (3-methanesulfonyl-phenyl)-naphthalen-2-



ylmethyl-amide


855
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
534



carboxylic acid (3-methanesulfonyl-phenyl)-pyridin-3-



ylmethyl-amide


856
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
534



carboxylic acid (3-methanesulfonyl-phenyl)-pyridin-2-



ylmethyl-amide


857
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
567



carboxylic acid (4-chloro-benzyl)-(3-methanesulfonyl-



phenyl)-amide


858
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
534



carboxylic acid (3-methanesulfonyl-phenyl)-pyridin-4-



ylmethyl-amide


859
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
483



carboxylic acid allyl-(3-methanesulfonyl-phenyl)-amide


860
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
552



carboxylic acid (3,5-dimethyl-isoxazol-4-ylmethyl)-(3-



methanesulfonyl-phenyl)-amide


861
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
551



carboxylic acid benzyl-[2-(2,6-dichloro-phenyl)-ethyl]-



amide


862
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
601



carboxylic acid [2-(2,6-dichloro-phenyl)-ethyl]-



naphthalen-2-ylmethyl-amide


863
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
552



carboxylic acid [2-(2,6-dichloro-phenyl)-ethyl]-pyridin-3-



ylmethyl-amide


864
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
552



carboxylic acid [2-(2,6-dichloro-phenyl)-ethyl]-pyridin-2-



ylmethyl-amide


865
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
585



carboxylic acid (4-chloro-benzyl)-[2-(2,6-dichloro-



phenyl)-ethyl]-amide


866
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
552



carboxylic acid [2-(2,6-dichloro-phenyl)-ethyl]-pyridin-4-



ylmethyl-amide


867
1-Benzyl-3-[1-(4-chloro-phenyl)-5-trifluoromethyl-1H-
394



pyrazol-4-yl]-urea


868
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
408



yl]-3-phenethyl-urea


869
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
426



yl]-3-[2-(4-fluoro-phenyl)-ethyl]-urea


870
Morpholine-4-carboxylic acid [1-(4-chloro-phenyl)-5-
374



trifluoromethyl-1H-pyrazol-4-yl]-amide


871
1-Butyl-3-[1-(4-chloro-phenyl)-5-trifluoromethyl-1H-
360



pyrazol-4-yl]-urea


872
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
422



yl]-3-(2-m-tolyl-ethyl)-urea


873
1-[2-(4-Chloro-phenyl)-ethyl]-3-[1-(4-chloro-phenyl)-5-
442



trifluoromethyl-1H-pyrazol-4-yl]-urea


874
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
422



yl]-3-(3-phenyl-propyl)-urea


875
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
372



yl]-3-cyclopentyl-urea


876
1-Benzo[1,3]dioxol-5-ylmethyl-3-[1-(4-chloro-phenyl)-5-
438



trifluoromethyl-1H-pyrazol-4-yl]-urea


877
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
409



yl]-1-methyl-1-pyridin-3-ylmethyl-urea


878
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
423



yl]-1-methyl-1-(2-pyridin-2-yl-ethyl)-urea


879
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
414



carboxylic acid 3-trifluoromethyl-benzylamide


880
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
378



carboxylic acid [2-(2-fluoro-phenyl)-ethyl]-amide


881
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
372



carboxylic acid (1H-benzoimidazol-2-yl)-amide


882
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
333



carboxylic acid pyridin-4-ylamide


883
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
428



carboxylic acid [2-(2,6-dichloro-phenyl)-ethyl]-amide


884
1-(3-Chloro-phenyl)-3-[1-(4-chloro-phenyl)-5-
414



trifluoromethyl-1H-pyrazol-4-yl]-urea


885
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
448



yl]-3-(4-trifluoromethyl-phenyl)-urea


886
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
371



yl]-3-isoxazol-3-yl-urea


887
1-(2-tert-Butyl-phenyl)-3-[1-(4-chloro-phenyl)-5-
436



trifluoromethyl-1H-pyrazol-4-yl]-urea


888
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
380



yl]-3-phenyl-urea


889
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
445



yl]-3-(2-pyrrol-1-yl-phenyl)-urea


890
3-(2-Chloro-phenyl)-5-methyl-isoxazole-4-carboxylic acid
480



[1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-



amide


891
1,3-Bis-[1-(4-chloro-phenyl)-5-trifluoromethyl-1H-
548



pyrazol-4-yl]-urea


892
4-Acetyl-[1,4]diazepane-1-carboxylic acid [1-(4-chloro-
429



phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide


893
1-Allyl-3-[1-(4-chloro-phenyl)-5-trifluoromethyl-1H-
344



pyrazol-4-yl]-urea


894
1-(2-Amino-benzyl)-3-[1-(4-chloro-phenyl)-5-
409



trifluoromethyl-1H-pyrazol-4-yl]-urea


895
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
445



yl]-3-(4-diethylamino-1-methyl-butyl)-urea


896
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
392



yl]-3-[2-(2-hydroxy-ethoxy)-ethyl]-urea


897
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
465



yl]-3-[2-(ethyl-m-tolyl-amino)-ethyl]-urea


898
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
415



yl]-3-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-urea


899
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
417



yl]-3-(2-morpholin-4-yl-ethyl)-urea


900
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
415



yl]-3-(2-piperidin-1-yl-ethyl)-urea


901
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
409



yl]-3-(2-pyridin-2-yl-ethyl)-urea


902
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
401



yl]-3-(2-pyrrolidin-1-yl-ethyl)-urea


903
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
420



yl]-3-(1H-indazol-6-yl)-urea


904
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
395



yl]-3-pyridin-3-ylmethyl-urea


905
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
395



yl]-3-pyridin-4-ylmethyl-urea


906
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
424



yl]-3-(2-hydroxy-2-phenyl-ethyl)-urea


907
1-[2-(4-Amino-phenyl)-ethyl]-3-[1-(4-chloro-phenyl)-5-
423



trifluoromethyl-1H-pyrazol-4-yl]-urea


908
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
446



yl]-3-(5-phenyl-2H-pyrazol-3-yl)-urea


909
(3-{3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-
461



4-yl]-ureido}-propyl)-carbamic acid tert-butyl ester


910
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
412



yl]-3-(3-imidazol-1-yl-propyl)-urea


911
1-(1-Benzyl-pyrrolidin-3-yl)-3-[1-(4-chloro-phenyl)-5-
463



trifluoromethyl-1H-pyrazol-4-yl]-urea


912
4-Benzyl-piperazine-1-carboxylic acid [1-(4-chloro-
463



phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide


913
4-(2-Chloro-phenyl)-piperazine-1-carboxylic acid [1-(4-
483



chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide


914
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
392



yl]-1,1-bis-(2-hydroxy-ethyl)-urea


915
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
403



yl]-3-(2-diethylamino-ethyl)-urea


916
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
417



yl]-3-(3-diethylamino-propyl)-urea


917
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
454



yl]-3-(2,3-dimethoxy-benzyl)-urea


918
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
454



yl]-3-(2,4-dimethoxy-benzyl)-urea


919
2,6-Dimethyl-morpholine-4-carboxylic acid [1-(4-chloro-
402



phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide


920
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
486



yl]-1,1-bis-pyridin-2-ylmethyl-urea


921
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
486



yl]-1,1-bis-pyridin-3-ylmethyl-urea


922
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
376



yl]-1-ethyl-1-(2-hydroxy-ethyl)-urea


923
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
423



yl]-1-ethyl-1-pyridin-4-ylmethyl-urea


924
v4-(2-Hydroxy-ethyl)-piperazine-1-carboxylic acid [1-(4-
417



chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide


925
4-Methyl-[1,4]diazepane-1-carboxylic acid [1-(4-chloro-
401



phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide


926
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
415



yl]-1-methyl-1-(1-methyl-piperidin-4-yl)-urea


927
4-Methyl-piperazine-1-carboxylic acid [1-(4-chloro-
387



phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide


928
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
378



yl]-3-(2-methylsulfanyl-ethyl)-urea


929
4-Pyrimidin-2-yl-piperazine-1-carboxylic acid [1-(4-
451



chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide


930
4-Benzo[1,3]dioxol-5-ylmethyl-piperazine-1-carboxylic
507



acid [1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-



yl]-amide


931
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
448



yl]-1-(2-cyano-ethyl)-1-pyridin-3-ylmethyl-urea


932
3-Hydroxy-pyrrolidine-1-carboxylic acid [1-(4-chloro-
374



phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide


933
4-Pyrrolidin-1-yl-piperidine-1-carboxylic acid [1-(4-
441



chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide


934
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
388



yl]-3-(tetrahydro-furan-2-ylmethyl)-urea


935
Thiazolidine-3-carboxylic acid [1-(4-chloro-phenyl)-5-
376



trifluoromethyl-1H-pyrazol-4-yl]-amide


936
Thiomorpholine-4-carboxylic acid [1-(4-chloro-phenyl)-5-
390



trifluoromethyl-1H-pyrazol-4-yl]-amide


937
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
414



yl]-3-(2-thiophen-2-yl-ethyl)-urea


938
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
400



yl]-3-thiophen-2-ylmethyl-urea


939
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [1-(4-
430



trifluoromethoxy-phenyl)-pyrrolidin-3-yl]-amide


940
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [1-(4-
430



trifluoromethoxy-phenyl)-pyrrolidin-3-yl]-amide


941
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [1-(3-
430



trifluoromethoxy-phenyl)-pyrrolidin-3-yl]-amide


942
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [1-(3-
430



trifluoromethoxy-phenyl)-pyrrolidin-3-yl]-amide


943
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [1-(3-
414



trifluoromethyl-phenyl)-pyrrolidin-3-yl]-amide


944
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [1-(3-
414



trifluoromethyl-phenyl)-pyrrolidin-3-yl]-amide


945
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
440



4-carboxylic acid 2,4-dimethoxy-benzylamide


946
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
424



4-carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide


947
1-(6-Chloro-pyridin-2-yl)-5-trifluorormethyl-1H-pyrazole-
384



4-carboxylic acid (3-fluoro-phenyl)-amide


948
[1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazol-
406



4-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone


949
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
396



4-carboxylic acid (3-methoxy-phenyl)-amide


950
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
406



4-carboxylic acid (2-isopropenyl-phenyl)-amide


951
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
381



4-carboxylic acid (pyridin-3-ylmethyl)-amide


952
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
462



4-carboxylic acid [2-(2,6-dichloro-phenyl)-ethyl]-amide


953
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
451



4-carboxylic acid [2-(ethyl-m-tolyl-amino)-ethyl]-amide


954
[4-(2-Chloro-phenyl)-piperazin-1-yl]-[1-(6-chloro-
469



pyridin-2-yl)-5-trifluoromethyl-1H-pyrazol-4-yl]-



methanone


955
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
449



4-carboxylic acid (1-benzyl-pyrrolidin-3-yl)-amide


956
(4-Benzyl-piperazin-1-yl)-[1-(6-chloro-pyridin-2-yl)-5-
449



trifluoromethyl-1H-pyrazol-4-yl]-methanone


957
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
407



carboxylic acid 2,4-dimethoxy-benzylamide


958
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
391



carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide


959
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
351



carboxylic acid (3-fluoro-phenyl)-amide


960
(3,4-Dihydro-2H-quinolin-1-yl)-(1-pyrimidin-2-yl-5-
373



trifluoromethyl-1H-pyrazol-4-yl)-methanone


961
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
363



carboxylic acid (3-methoxy-phenyl)-amide


962
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
373



carboxylic acid (2-isopropenyl-phenyl)-amide


963
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
348



carboxylic acid (pyridin-3-ylmethyl)-amide


964
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
429



carboxylic acid [2-(2,6-dichloro-phenyl)-ethyl]-amide


965
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
418



carboxylic acid [2-(ethyl-m-tolyl-amino)-ethyl]-amide


966
[4-(2-Chloro-phenyl)-piperazin-1-yl]-(1-pyrimidin-2-yl-5-
436



trifluoromethyl-1H-pyrazol-4-yl)-methanone


967
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
416



carboxylic acid (1-benzyl-pyrrolidin-3-yl)-amide


968
(4-Benzyl-piperazin-1-yl)-(1-pyrimidin-2-yl-5-
416



trifluoromethyl-1H-pyrazol-4-yl)-methanone


969
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
489



pyrazole-4-carboxylic acid 2,4-dimethoxy-benzylamide


970
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
473



pyrazole-4-carboxylic acid (benzo[1,3]dioxol-5-



ylmethyl)-amide


971
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
433



pyrazole-4-carboxylic acid (3-fluoro-phenyl)-amide


972
(3,4-Dihydro-2H-quinolin-1-yl)-[1-(4-trifluoromethoxy-
455



phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-methanone


973
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
445



pyrazole-4-carboxylic acid (3-methoxy-phenyl)-amide


974
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
455



pyrazole-4-carboxylic acid (2-isopropenyl-phenyl)-amide


975
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
430



pyrazole-4-carboxylic acid (pyridin-3-ylmethyl)-amide


976
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
511



pyrazole-4-carboxylic acid [2-(2,6-dichloro-phenyl)-



ethyl]-amide


977
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
500



pyrazole-4-carboxylic acid [2-(ethyl-m-tolyl-amino)-



ethyl]-amide


978
[4-(2-Chloro-phenyl)-piperazin-1-yl]-[1-(4-
518



trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-pyrazol-4-



yl]-methanone


979
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
498



pyrazole-4-carboxylic acid (1-benzyl-pyrrolidin-3-yl)-



amide


980
(4-Benzyl-piperazin-1-yl)-[1-(4-trifluoromethoxy-phenyl)-
498



5-trifluoromethyl-1H-pyrazol-4-yl]-methanone


981
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
406



carboxylic acid 2,4-dimethoxy-benzylamide


982
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
390



carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide


983
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
350



carboxylic acid (3-fluoro-phenyl)-amide


984
(3,4-Dihydro-2H-quinolin-1-yl)-(1-pyridin-2-yl-5-
372



trifluoromethyl-1H-pyrazol-4-yl)-methanone


985
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
362



carboxylic acid (3-methoxy-phenyl)-amide


986
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
372



carboxylic acid (2-isopropenyl-phenyl)-amide


987
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
347



carboxylic acid (pyridin-3-ylmethyl)-amide


988
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
417



carboxylic acid [2-(ethyl-m-tolyl-amino)-ethyl]-amide


989
[4-(2-Chloro-phenyl)-piperazin-1-yl]-(1-pyridin-2-yl-5-
435



trifluoromethyl-1H-pyrazol-4-yl)-methanone


990
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
415



carboxylic acid (1-benzyl-pyrrolidin-3-yl)-amide


991
(4-Benzyl-piperazin-1-yl)-(1-pyridin-2-yl-5-
415



trifluoromethyl-1H-pyrazol-4-yl)-methanone


992
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
450



4-carboxylic acid (2-trifluoromethoxy-phenyl)-amide


993
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
422



4-carboxylic acid (4-tert-butyl-phenyl)-amide


994
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
472



4-carboxylic acid bis-pyridin-2-ylmethyl-amide


995
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
428



4-carboxylic acid [2-(4-chloro-phenyl)-ethyl]-amide


996
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
412



4-carboxylic acid [2-(4-fluoro-phenyl)-ethyl]-amide


997
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
398



4-carboxylic acid (4-fluoro-phenyl)-methyl-amide


998
4-{[1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-
438



pyrazole-4-carbonyl]-amino}-benzoic acid ethyl ester


999
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
431



4-carboxylic acid (2-pyrrol-1-yl-phenyl)-amide


1000
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
401



4-carboxylic acid (5-chloro-pyridin-2-yl)-amide


1001
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole-
417



4-carboxylic acid isoquinolin-1-ylamide


1002
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
417



carboxylic acid (2-trifluoromethoxy-phenyl)-amide


1003
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
389



carboxylic acid (4-tert-butyl-phenyl)-amide


1004
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
439



carboxylic acid bis-pyridin-2-ylmethyl-amide


1005
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
395



carboxylic acid [2-(4-chloro-phenyl)-ethyl]-amide


1006
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
379



carboxylic acid [2-(4-fluoro-phenyl)-ethyl]-amide


1007
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
365



carboxylic acid (4-fluoro-phenyl)-methyl-amide


1008
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
411



carboxylic acid (3-methanesulfonyl-phenyl)-amide


1009
4-[(1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
405



carbonyl)-amino]-benzoic acid ethyl ester


1010
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
398



carboxylic acid (2-pyrrol-1-yl-phenyl)-amide


1011
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
368



carboxylic acid (5-chloro-pyridin-2-yl)-amide


1012
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
384



carboxylic acid isoquinolin-1-ylamide


1013
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
499



pyrazole-4-carboxylic acid (2-trifluoromethoxy-phenyl)-



amide


1014
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
471



pyrazole-4-carboxylic acid (4-tert-butyl-phenyl)-amide


1015
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
521



pyrazole-4-carboxylic acid bis-pyridin-2-ylmethyl-amide


1016
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
477



pyrazole-4-carboxylic acid [2-(4-chloro-phenyl)-ethyl]-



amide


1017
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
461



pyrazole-4-carboxylic acid [2-(4-fluoro-phenyl)-ethyl]-



amide


1018
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
447



pyrazole-4-carboxylic acid (4-fluoro-phenyl)-methyl-



amide


1019
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
493



pyrazole-4-carboxylic acid (3-methanesulfonyl-phenyl)-



amide


1020
4-{[1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
487



pyrazole-4-carbonyl]-amino}-benzoic acid ethyl ester


1021
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
480



pyrazole-4-carboxylic acid (2-pyrrol-1-yl-phenyl)-amide


1022
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
450



pyrazole-4-carboxylic acid (5-chloro-pyridin-2-yl)-amide


1023
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
466



pyrazole-4-carboxylic acid isoquinolin-1-ylamide


1024
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
416



carboxylic acid (2-trifluoromethoxy-phenyl)-amide


1025
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
388



carboxylic acid (4-tert-butyl-phenyl)-amide


1026
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
438



carboxylic acid bis-pyridin-2-ylmethyl-amide


1027
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
394



carboxylic acid [2-(4-chloro-phenyl)-ethyl]-amide


1028
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
378



carboxylic acid [2-(4-fluoro-phenyl)-ethyl]-amide


1029
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
364



carboxylic acid (4-fluoro-phenyl)-methyl-amide


1030
4-[(1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
404



carbonyl)-amino]-benzoic acid ethyl ester


1031
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
397



carboxylic acid (2-pyrrol-1-yl-phenyl)-amide


1032
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
367



carboxylic acid (5-chloro-pyridin-2-yl)-amide


1033
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4-
383



carboxylic acid isoquinolin-1-ylamide


1034
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
450



carboxylic acid [2-(ethyl-m-tolyl-amino)-ethyl]-amide


1035
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
448



carboxylic acid (1-benzyl-pyrrolidin-3-yl)-amide


1036
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
448



carboxylic acid (1-benzyl-pyrrolidin-3-yl)-amide


1037
1-(1-Benzyl-pyrrolidin-3-yl)-3-[1-(4-chloro-phenyl)-5-
463



trifluoromethyl-1H-pyrazol-4-yl]-urea


1038
1-(1-Benzyl-pyrrolidin-3-yl)-3-[1-(4-chloro-phenyl)-5-
463



trifluoromethyl-1H-pyrazol-4-yl]-urea


1039
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
462



carboxylic acid (1-benzyl-piperidin-4-yl)-amide


1040
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
372



carboxylic acid piperidin-4-ylamide


1041
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
451



carboxylic acid (1-sulfamoyl-piperidin-4-yl)-amide


1042
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
479



carboxylic acid (1-dimethylsulfamoyl-piperidin-4-yl)-



amide


1044
4-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-
444



4-carbonyl]-amino}-piperidine-1-carboxylic acid ethyl



ester


1045
{1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-
472



4-carbonyl]-piperidin-4-yl}-carbamic acid tert-butyl ester


1046
(4-Amino-piperidin-1-yl)-[1-(4-chloro-phenyl)-5-
372



trifluoromethyl-1H-pyrazol-4-yl]-methanone


1049
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
399



carboxylic acid (3-chloro-phenyl)-amide


1050
3-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-
437



4-carbonyl]-amino}-benzoic acid ethyl ester


1052
3-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-
409



4-carbonyl]-amino}-benzoic acid


1053
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
460



carboxylic acid [3-(3,5-dimethyl-isoxazol-4-yl)-phenyl]-



amide


1054
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
444



carboxylic acid (3-sulfamoyl-phenyl)-amide


1055
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
472



carboxylic acid (3-dimethylsulfamoyl-phenyl)-amide


1056
(4-Benzylamino-piperidin-1-yl)-[1-(4-chloro-phenyl)-5-
462



trifluoromethyl-1H-pyrazol-4-yl]-methanone


1057
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
480



[4-(4-fluoro-benzylamino)-piperidin-1-yl]-methanone


1058
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
492



[4-(4-methoxy-benzylamino)-piperidin-1-yl]-methanone


1059
[4-(4-Chloro-benzylamino)-piperidin-1-yl]-[1-(4-chloro-
496



phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-methanone


1060
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
480



carboxylic acid [1-(4-fluoro-benzyl)-piperidin-4-yl]-amide


1061
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
496



carboxylic acid [1-(3-chloro-benzyl)-piperidin-4-yl]-



amide


1062
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
480



carboxylic acid [1-(2-fluoro-benzyl)-piperidin-4-yl]-amide


1063
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
546



carboxylic acid [1-(4-trifluoromethoxy-benzyl)-piperidin-



4-yl]-amide


1064
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
554



carbonyl]-piperidine-2-carboxylic acid (3-



methanesulfonyl-phenyl)-amide


1065
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
373



(4-hydroxy-piperidin-1-yl)-methanone


1066
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
491



[2-(5-fluoro-1H-benzoimidazol-2-yl)-piperidin-1-yl]-



methanone


1067
[2-(1H-Benzoimidazol-2-yl)-piperidin-1-yl]-[1-(4-chloro-
473



phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-methanone


1068
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
427



carboxylic acid (3-methanesulfonyl-phenyl)-amide


1069
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
445



carboxylic acid (3-methanesulfonyl-phenyl)-amide


1070
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
377



carboxylic acid phenethyl-amide


1071
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
395



carboxylic acid phenethyl-amide


1072
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
377



carboxylic acid benzyl-methyl-amide


1073
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
395



carboxylic acid benzyl-methyl-amide


1074
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
431



carboxylic acid 3-trifluoromethyl-benzylamide


1075
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
449



carboxylic acid 3-trifluoromethyl-benzylamide


1076
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
504



carbonyl]-piperidine-2-carboxylic acid phenethyl-amide


1077
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
504



carbonyl]-piperidine-2-carboxylic acid benzyl-methyl-



amide


1078
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
558



carbonyl]-piperidine-2-carboxylic acid 3-trifluoromethyl-



benzylamide


1079
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
446



carboxylic acid (1-benzyl-pyrrolidin-3-yl)-methyl-amide


1080
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
464



carboxylic acid (1-benzyl-pyrrolidin-3-yl)-methyl-amide


1081
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
512



pyrazole-4-carboxylic acid (1-benzyl-pyrrolidin-3-yl)-



methyl-amide


1082
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
450



carboxylic acid (5-diisopropylamino-pyrimidin-2-yl)-



amide


1083
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
468



carboxylic acid (5-diisopropylamino-pyrimidin-2-yl)-



amide


1084
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
516



pyrazole-4-carboxylic acid (5-diisopropylamino-



pyrimidin-2-yl)-amide


1085
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
428



carboxylic acid (3-sulfamoyl-phenyl)-amide


1086
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
446



carboxylic acid (3-sulfamoyl-phenyl)-amide


1087
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
494



pyrazole-4-carboxylic acid (3-sulfamoyl-phenyl)-amide


1088
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
443



carboxylic acid (2-chloro-pyrimidin-5-yl)-amide


1089
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
448



carboxylic acid (3-thiazol-2-yl-phenyl)-amide


1090
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
461



carboxylic acid [3-(3-methyl-5-oxo-4,5-dihydro-pyrazol-



1-yl)-phenyl]-amide


1091
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
482



carboxylic acid (3-benzooxazol-2-yl-phenyl)-amide


1092
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
408



carboxylic acid (3-carbamoyl-phenyl)-amide


1093
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
408



carboxylic acid (3-dimethylamino-phenyl)-amide


1094
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
473



carboxylic acid [3-(2-hydroxy-ethanesulfonyl)-phenyl]-



amide


1095
4-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-
472



4-carbonyl]-amino}-piperidine-1-carboxylic acid tert-



butyl ester


1096
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
429



carboxylic acid (2-methyl-5-phenyl-2H-pyrazol-3-yl)-



amide


1097
(4-Benzyl-piperazin-1-yl)-[1-(3-fluoro-phenyl)-5-
432



trifluoromethyl-1H-pyrazol-4-yl]-methanone


1098
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
350



carboxylic acid pyridin-4-ylamide


1099
Biphenyl-3-carboxylic acid (2-methyl-5-phenyl-2H-
353



pyrazol-3-yl)-amide


1100
Biphenyl-4-carboxylic acid (2-methyl-5-phenyl-2H-
353



pyrazol-3-yl)-amide


1101
4′-Chloro-biphenyl-3-carboxylic acid (2-methyl-5-phenyl-
387



2H-pyrazol-3-yl)-amide


1102
3-{[1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
456



carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl



ester


1103
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
447



carboxylic acid (2-methyl-5-phenyl-2H-pyrazol-3-yl)-



amide


1104
(4-Benzyl-piperazin-1-yl)-[1-(3,4-difluoro-phenyl)-5-
450



trifluoromethyl-1H-pyrazol-4-yl]-methanone


1105
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
368



carboxylic acid pyridin-4-ylamide


1106
3-{[1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-
474



pyrazole-4-carbonyl]-amino}-piperidine-1-carboxylic acid



tert-butyl ester


1107
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
514



carboxylic acid [3-(morpholine-4-sulfonyl)-phenyl]-amide


1108
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
495



pyrazole-4-carboxylic acid (2-methyl-5-phenyl-2H-



pyrazol-3-yl)-amide


1109
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
416



pyrazole-4-carboxylic acid pyridin-4-ylamide


1110
3-{[1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-
522



pyrazole-4-carbonyl]-amino}-piperidine-1-carboxylic acid



tert-butyl ester


1111
Methanesulfonic acid 1-[1-(4-chloro-phenyl)-5-
451



trifluoromethyl-1H-pyrazole-4-carbonyl]-piperidin-4-yl



ester


1112
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
458



carboxylic acid (3-methylsulfamoyl-phenyl)-amide


1113
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
442



carboxylic acid (3-pyridin-2-yl-phenyl)-amide


1114
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
442



carboxylic acid (3-pyridin-3-yl-phenyl)-amide


1115
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
442



carboxylic acid (3-pyridin-4-yl-phenyl)-amide


1116
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
428



carboxylic acid (3-sulfamoyl-phenyl)-amide


1117
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
497



carboxylic acid (3-trifluoromethanesulfonyl-phenyl)-



amide


1118
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
458



carboxylic acid (3-methanesulfonylamino-phenyl)-amide


1119
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
433



carboxylic acid [3-(2H-tetrazol-5-yl)-phenyl]-amide


1120
[(3-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-



4-carbonyl]-amino}-phenyl)-imino-methyl]-carbamic acid



tert-butyl ester


1121
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-



carboxylic acid (3-carbamimidoyl-phenyl)-amide


1122
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
380



carboxylic acid (3-amino-phenyl)-amide


1123
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-



carboxylic acid (3-ureido-phenyl)-amide


1127
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
444



carboxylic acid (4-sulfamoyl-phenyl)-amide


1130
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
422



carboxylic acid (3-acetylamino-phenyl)-amide


1131
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
484



carboxylic acid (3-cyclopropylsulfamoyl-phenyl)-amide


1132
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
449



(4-pyridin-2-ylmethyl-piperazin-1-yl)-methanone


1133
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
449



(4-pyridin-3-ylmethyl-piperazin-1-yl)-methanone


1134
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
449



(4-pyridin-4-ylmethyl-piperazin-1-yl)-methanone


1135
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-
469



[4-(1-methyl-piperidin-3-ylmethyl)-piperazin-1-yl]-



methanone


1136
2-Phenyl-2H-pyrazole-3-carboxylic acid pyridin-4-
264



ylamide


1137
(4-Benzyl-piperazin-1-yl)-(2-phenyl-2H-pyrazol-3-yl)-
346



methanone


1138
2-Phenyl-2H-pyrazole-3-carboxylic acid (3-
341



methanesulfonyl-phenyl)-amide


1139
2-Phenyl-2H-pyrazole-3-carboxylic acid (1H-
303



benzoimidazol-2-yl)-amide


1140
2-Phenyl-2H-pyrazole-3-carboxylic acid 3-
345



trifluoromethyl-benzylamide


1141
2-Phenyl-2H-pyrazole-3-carboxylic acid (2-methyl-5-
343



phenyl-2H-pyrazol-3-yl)-amide


1142
2-Phenyl-2H-pyrazole-3-carboxylic acid (3-sulfamoyl-
342



phenyl)-amide


1143
2-Phenyl-2H-pyrazole-3-carboxylic acid (1-benzyl-
360



piperidin-4-yl)-amide


1144
2-Phenyl-2H-pyrazole-3-carboxylic acid (1-benzyl-
346



pyrrolidin-3-yl)-amide


1145
2-Phenyl-2H-pyrazole-3-carboxylic acid (1-benzyl-
346



pyrrolidin-3-yl)-amide


1146
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
411



carboxylic acid (3-methylsulfanyl-phenyl)-amide


1147
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
427



carboxylic acid (3-methanesulfinyl-phenyl)-amide


1148
3-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole
445



4-carbonyl]-amino}-benzenesulfonic acid


1151
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
577



carboxylic acid {3-[(methanesulfonylimino-phenoxy-



methyl)-amino]-phenyl}-amide


1152
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
500



carboxylic acid {3-[(amino-methanesulfonylimino-



methyl)-amino]-phenyl}-amide


1153
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
514



carboxylic acid {3-[(methanesulfonylimino-methylamino-



methyl)-amino]-phenyl}-amide


1154
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
540



carboxylic acid {3-[(cyclopropylamino-



methanesulfonylimino-methyl)-amino]-phenyl}-amide


1155
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
528



carboxylic acid {3-[(dimethylamino-



methanesulfonylimino-methyl)-amino]-phenyl}-amide


1156
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
556



carboxylic acid (3-{[(isopropyl-methyl-amino)-



methanesulfonylimino-methyl]-amino}-phenyl)-amide


1157
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
594



carboxylic acid [3-(2,4-dimethoxy-benzylsulfamoyl)-



phenyl]-amide


1158
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
555



carboxylic acid [3-(2-piperidin-1-yl-ethylsulfamoyl)-



phenyl]-amide


1159
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
557



carboxylic acid [3-(3-diethylamino-propylsulfamoyl)-



phenyl]-amide


1160
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
594



carboxylic acid [3-(2,3-dimethoxy-benzylsulfamoyl)-



phenyl]-amide


1161
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
569



carboxylic acid {3-[3-(2-oxo-pyrrolidin-1-yl)-



propylsulfamoyl]-phenyl}-amide


1162
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
605



carboxylic acid {3-[2-(ethyl-m-tolyl-amino)-



ethylsulfamoyl]-phenyl}-amide


1163
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
514



carboxylic acid [3-(3-hydroxy-pyrrolidine-1-sulfonyl)-



phenyl]-amide


1164
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
500



carboxylic acid (3-butylsulfamoyl-phenyl)-amide


1165
[3-(3-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-
601



pyrazole-4-carbonyl]-amino}-benzenesulfonylamino)-



propyl]-carbamic acid tert-butyl ester


1166
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
514



carboxylic acid [3-(3-hydroxy-pyrrolidine-1-sulfonyl)-



phenyl]-amide


1167
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
502



carboxylic acid [3-(2-hydroxy-propylsulfamoyl)-phenyl]-



amide


1168
(4-Benzyl-piperazin-1-yl)-[1-(4-chloro-phenyl)-5-
448



trifluoromethyl-1H-pyrazol-4-yl]-methanone


1169
(4-Benzyl-4-hydroxy-piperidin-1-yl)-[1-(4-chloro-
463



phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-methanone


1170
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
555



carboxylic acid {3-[(1-ethyl-pyrrolidin-2-ylmethyl)-



sulfamoyl]-phenyl}-amide


1171
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
543



carboxylic acid [3-(2-diethylamino-ethylsulfamoyl)-



phenyl]-amide


1172
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
563



carboxylic acid {3-[2-(4-amino-phenyl)-ethylsulfamoyl]-



phenyl}-amide


1173
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
541



carboxylic acid [3-(2-pyrrolidin-1-yl-ethylsulfamoyl)-



phenyl]-amide


1174
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
535



carboxylic acid {3-[(pyridin-3-ylmethyl)-sulfamoyl]-



phenyl}-amide


1175
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
515



carboxylic acid [3-(2-dimethylamino-ethylsulfamoyl)-



phenyl]-amide


1176
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
530



carboxylic acid [3-(thiomorpholine-4-sulfonyl)-phenyl]-



amide


1177
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
541



carboxylic acid [3-(4-methyl-[1,4]diazepane-1-sulfonyl)-



phenyl]-amide


1178
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
527



carboxylic acid [3-(4-methyl-piperazine-1-sulfonyl)-



phenyl]-amide


1179
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
582



carboxylic acid {3-[2-(3-chloro-phenyl)-ethylsulfamoyl]-



phenyl}-amide


1180
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
563



carboxylic acid {3-[methyl-(2-pyridin-2-yl-ethyl)-



sulfamoyl]-phenyl}-amide


1181
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
472



carboxylic acid (3-ethylsulfamoyl-phenyl)-amide


1182
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
502



carboxylic acid {3-[(2-hydroxy-ethyl)-methyl-sulfamoyl]-



phenyl}-amide


1183
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
500



carboxylic acid (3-diethylsulfamoyl-phenyl)-amide


1184
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
500



carboxylic acid (6-methanesulfonyl-benzothiazol-2-yl)-



amide


1185
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
458



carboxylic acid (2-methyl-3-sulfamoyl-phenyl)-amide


1186
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
458



carboxylic acid (2-sulfamoylmethyl-phenyl)-amide


1187
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
478



carboxylic acid (2-chloro-5-sulfamoyl-phenyl)-amide


1188
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
465



carboxylic acid (4-methyl-5-sulfamoyl-thiazol-2-yl)-



amide









It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to included within the spirit and purview of this application and are considered within the scope of the appended claims. All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety for all purposes.

## Claims

1. A compound having the formula:




or a pharmaceutically acceptable salt thereof, wherein
R1 and R3 are each members independently selected from hydrogen, (C1–C4)alkyl, (C1–C4)haloalkyl, (C1–C6)heteroalkyl, amino, halo, cyano, nitro, and hydroxy;
R2 is a member selected from aryl and aryl(C1–C4)alkyl;
Y is




 wherein
X is O;
R4 is a member selected from hydrogen, (C1–C10)alkyl, (C3–C7)cycloalkyl, (C1–C8)heteroalkyl, aryl, heteroaryl, aryl(C1–C4)alkyl, heteroaryl(C1–C4)alkyl and (C3–C8)heterocycloalkyl; and
R5 is a member selected from heteroaryl, heteroaryl(C1–C4)alkyl and (C3–C8)heterocycloalkyl.

2. The compound of claim 1 having the formula:

3. The compound of claim 2 wherein
R1 and R3 are each members independently selected from hydrogen, (C1–C4)alkyl, (C1–C4)haloalkyl and (C1–C5)heteroalkyl.

4. The compound of claim 3 wherein R2 is aryl.

5. The compound of claim 4 wherein R3 is hydrogen.

6. The compound according to claim 5 wherein R1 is a member selected from hydrogen, (C1–C4)alkyl, and (C1–C4)haloalkyl.

7. The compound according to claim 2 wherein R4 is a member selected from heteroaryl and heterocycloalkyl.

8. A compound having the formula:




or a pharmaceutically acceptable salt thereof, wherein
R1 and R3 are each members independently selected from hydrogen, (C1–C4)alkyl, (C1–C4)haloalkyl, (C1–C6)heteroalkyl, amino, halo, cyano, nitro, and hydroxy;
R2 is a member selected from aryl and aryl(C1–C4)alkyl;
Y is




 wherein
X is O;
R4 has a formula which is a member selected from:




 and heteroaryl(C1–C4)alkyl
 wherein
k is an integer from 1 to 3;
M is a member selected from NR10, O and S
wherein
R10 is a member selected from hydrogen, (C1–C6)alkyl, (C1–C8) heteroalkyl aryl, heteroaryl and (C3–C8)cycloalkyl;

A, B, D, and G are independently members selected from N, N-oxide and CR11 with the proviso that at most three of A, B, D, and G is N;
and at most one of A, B, D, and G is N-oxide

wherein
R11 is a member selected from hydrogen, halo, amino, hydroxy, cyano, nitro, (C1–C4)alkyl, (C3–C7)cycloalkyl, (C1–C7)heteroalkyl, aryl, heteroaryl, (C3–C8)heterocycloalkyl, alkoxy, acyl, —C(NR12)R13, —SO2R15, —SO2NR13R14, —NR12SOR15, —NR12SO2NR13R14, —NR12C(N—CN)NR13R14, —NR12C(N—SO2R15)NR13R14, —NR12C(N—COR15)N13R14, —CONR13R14, —NR12(C═CH—NO2)NR13R14, —NR12CONR13R14, —NR12CO—OR15, —OCONR13R14 and R11 and R2a taken together with the carbon atoms to which they are attached optionally form a 4- to 8-membered heterocycloalkyl group with the proviso that A is CR11 
wherein
R11a is a member selected from (C1–C6)alkyl, (C3–C7)cycloalkyl, (C3–C8)heterocycloalkyl, aryl and heteroaryl;
R12, R13 and R14 are members independently selected from hydrogen, (C1–C8)alkyl, (C3–C7)cycloalkyl, (C1–C8)heteroalkyl, aryl, heteroaryl, (C3–C8)heterocycloalkyl, aryl(C1–C4)alkyl, heteroaryl(C1–C4)alkyl, amino(C1–C4)alkyl and when R13 and R14 are attached to the same nitrogen atom, they are optionally combined to form a 5-, 6- or 7-membered ring;
R15 is a member selected from (C1–C8)alkyl, (C3–C8)cycloalkyl, (C1–C8)heteroalkyl, aryl, heteroaryl and (C3–C8)heterocycloalkyl;


R5 is a member selected from hydrogen and (C1–C4)alkyl; and R5 and R11 taken together with the atoms to which that are attached optionally form a 4- to 8-membered heterocycloalkyl ring with the proviso that A is CR11.

9. The compound of claim 8 wherein R1 and R3 are each members independently selected from hydrogen, (C1–C4)alkyl, (C1–C4)haloalkyl and (C1–C5)heteroalkyl.

10. The compound of claim 9 wherein R2 is aryl.

11. The compound of claim 9 wherein one only of A, B, G, or D is an N or N-oxide.

12. A compound having the formula:




or a pharmaceutically acceptable salt thereof, wherein
R1 and R3 are each members independently selected from hydrogen, (C1–C4)alkyl, (C1–C4)haloalkyl, (C1–C6)heteroalkyl, amino, halo, cyano, nitro, and hydroxy;
R2 is a member selected from aryl and aryl(C1–C4)alkyl, and heteroaryl(C1–C4)alkyl;
Y is a member selected from:





R4 has a formula which is a member selected from:






 wherein
W is a member selected from S, SO and SO2;
n is an integer from 0 to 4;
R2a and R2b are members independently selected from hydrogen and (C1–C4)alkyl, and R2a and R2b taken together with the carbon atom to which they are attached optionally form a 3- to 8-membered carbocyclic or heterocycloalkyl ring;
R15 is a member selected from (C1–C4)alkyl, (C1–C6)alkenyl, (C3–C7)cycloalkyl, aryl, heteroaryl, (C1–C8)heteroalkyl, NR16R17 
wherein
R16 and R17 are members independently selected from hydrogen, (C1–C4)alkyl, (C1–C7)cycloalkyl, (C1–C8)heteroalkyl, (C3–C8)heterocycloalkyl, aryl, heteroaryl, aryl(C1–C4)alkyl, heteroaryl(C1–C4)alkyl, amino(C1–C4)alkyl, with the proviso that when R15 is amino W is SO2;

T1, T2, T3 and T4 are each members independently selected from hydrogen, halo, amino, cyano, nitro, (C1–C4)alkyl, (C3–C8)cycloalkyl, (C1–C4)haloalkyl, alkoxy, fluoro(C1–C4)alkoxy, (C1–C7)cycloalkyl, (C1–C7)heteroalkyl, aryl and heteroaryl, and T1 and T2 taken together with the carbon atoms to which they are attached optionally form a 4- to 8-membered carbocyclic or heterocycloalkyl ring; T2 and T3 taken together with the carbon atoms to which they are attached optionally form a 4- to 8-membered carbocyclic or heterocycloalkyl ring; T3 and R15 taken together with the atoms to which they are attached optionally form a 4- to 8-membered carbocyclic or heterocycloalkyl ring; and T4 and R15 taken together with the atoms to which they are attached optionally form a 4-to 8-membered carbocyclic or heterocycloalkyl ring; and
R5 is a member selected from hydrogen and (C1–C4)alkyl; R5 and T1 taken together with the atoms to which they are attached optionally form a 4- to 8-membered heterocycloalkyl ring, and R5 and T4 taken together with the atoms to which they are attached optionally form a 4- to 8-membered heterocycloalkyl ring.

13. The compound of claim 12 wherein R1 and R3 are each members independently selected from hydrogen, (C1–C4)alkyl, (C1–C4)haloalkyl and (C1–C5)heteroalkyl.

14. The compound of claim 12 wherein R2 is aryl.

15. The compound of claim 13 wherein W is SO2; and R11 is selected from substituted or unsubstituted (C1–C4)alkyl and NR16R17; and n is 0.

16. A method of treating pain through inhibition of a voltage-dependent sodium channel, said method comprising administering to a subject in need of such treatment, an effective amount of a compound having the formula:




or a pharmaceutically acceptable salt thereof, wherein
R1 and R3 are each members independently selected from hydrogen, (C1–C4)alkyl, (C1–C4)haloalkyl, (C1–C6)heteroalkyl, amino, halo, cyano, nitro, and hydroxy;
R2 is a member selected from aryl, and aryl(C1–C4)alkyl;
Y is




 wherein
X is O;
R4 is a member selected from hydrogen, (C1–C10)alkyl, (C3–C7)cycloalkyl, (C1–C8)heteroalkyl, aryl, heteroaryl, aryl(C1–C4)alkyl, heteroaryl(C 1–C4)alkyl and (C3–C8)heterocycloalkyl; and
R5 is a member selected from heteroaryl, heteroaryl(C1–C4)alkyl and (C3–C8)heterocycloalkyl.

17. The method according to claim 16, said compound having the formula:

18. The method according to claim 16, wherein said pain is selected from inflammatory pain, neuropathic pain and combinations thereof.

19. A composition comprising a pharmaceutically acceptable excipient and a compound having the formula:




or a pharmaceutically acceptable salt thereof wherein
R1 and R3 are each members independently selected from hydrogen, (C1–C4)alkyl, (C1–C4)haloalkyl, (C1–C6)heteroalkyl, amino, halo, cyano, nitro, and hydroxy;
R2 is a member selected from aryl and aryl(C1–C4)alkyl;
Y is




 wherein
X is O;
R4 is a member selected from hydrogen, (C1–C10)alkyl, (C3–C7)cycloalkyl, (C1–C8)heteroalkyl, aryl, heteroaryl, aryl(C1–C4)alkyl, heteroaryl(C1–C4)alkyl and (C3–C8)heterocycloalkyl; and
R5 is a member selected from heteroaryl, heteroaryl(C1–C4)alkyl and (C3–C8)heterocycloalkyl.

20. The composition of claim 19, wherein the compound has the formula:

21. The composition of claim 20, wherein R1 and R3 are each members independently selected from hydrogen, (C1–C4)alkyl, (C1–C4)haloalkyl and (C1–C5)heteroalkyl.

22. The composition of claim 21 wherein R2 is aryl.

23. The composition of claim 22, wherein R3 is hydrogen and R1 is a member selected from hydrogen, (C1–C4)alkyl, and (C1–C4)haloalkyl.

24. The composition of claim 20 wherein R4 is a member selected from heteroaryl and heterocycloalkyl.

25. A composition comprising a pharmaceutically acceptable excipient and a compound of claim 8.

26. The composition of claim 25 wherein R1 and R3 are each members independently selected from hydrogen, (C1–C4)alkyl, (C1–C4)haloalkyl and (C1–C5)heteroalkyl.

27. The composition of claim 26, wherein R2 is aryl.

28. The composition of claim 25, wherein one only of A, B, G or D is an N or N-oxide.

29. A composition comprising a pharmaceutically acceptable excipient and a compound of claim 12.

30. The composition of claim 29 wherein R1 and R3 are each members independently selected from hydrogen, (C1–C4)alkyl, (C1–C4)haloalkyl and (C1–C5)heteroalkyl.

31. The composition of claim 29 wherein R2 aryl.

32. The composition of claim 30 wherein W is SO2; and R11 is selected from substituted or unsubstituted (C1–C4)alkyl and NR16R17; and n is 0.

33. The composition of claim 19, wherein the compound is formulated for oral administration.

34. The composition of claim 25, wherein the compound is formulated for oral administration.

35. The composition of claim 29, wherein the compound is formulated for oral administration.

36. The method of claim 16, wherein the subject is human.

37. A method of treating pain in a human subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of claim 1.

38. A method of treating pain in a human subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of claim 8.

39. A method of treating pain in a human subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of claim 10.

40. A method of treating pain in a human subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of claim 12.

41. A method of treating pain in a human subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of claim 14.