PYRAZOLE INHIBITORS OF CYTOKINE PRODUCTION

Abstract: Compounds having formula (I) are useful for treating diseases that are prevented by or ameliorated with Interleukin-2, Interleukin-4, or Interleukin-5 production inhibitors.

Description: PYRAZOLE INHIBITORS OF CYTOKINE PRODUCTION Technical Field The present invention relates to organic compounds and compositions that are cytokine synthesis inhibitors, processes for making such compounds, synthetic intermediates employed in these processes, and methods for inhibiting cytokine production in a mammal. Background of The Invention Therapeutic control of the immune system is the goal of many approaches toward the treatment of autoimmune diseases that differ in organ specific involvement, pathogenic cofactors, response to treatment and prognosis. They range from diseases with "spontaneous" onset such as rheumatoid arthritis to rejection reactions after allograft organ transplantation. Interleukin 2 (IL-2), a lymphokine produced by activated T-cells, is a key regulator of immune and inflammatory responses. It promotes T cell proliferation in vitro and differentiation of B cells, activated macrophages, NK cells and LAK cells. The central importance of IL-2 in initiating adaptive immune responses such as the rejection of tissue grafts is well-illustrated by drugs that are most commonly used to suppress undesirable effects such as the rejection of tissue grafts. The drugs cyclosporin A and FK506 inhibit IL-2 production by disrupting signalling initiated through the T-cell receptor. The drug rapamycin also inhibits signalling through the T cell receptor. Cyclosporin A and rapamycin act synergistically to inhibit immune responses by preventing the IL-2 driven clonal expansion of T cells (Brazelton and Morris, Current Opinion in Immunology 8,, 710 (1996)). Compounds of this invention, due to their ability to inhibit IL-2 production, can be anticipated to demonstrate therapeutic efficacy in disease states where IL-2 is a key orchestrator of the immune response such as rheumatoid arthritis, atopic dermatitis, psoriasis and the rejection of tissue grafts. Increased local elaboration of the Th2-type cytokines Interleukin-5 (IL-5) and Interleukin-4 (IL-4) has clearly been implicated in the pathogenesis of atopic asthma (Am. J.Respir. Crit. Care Med. 154. 1497 (1996)). IL-5 has selective biologic effects on eosinophils and their precursors and may regulate selective accumulation of these cells in the asthmatic bronchial mucosa. IL-4 is an essential co-factor for IgE switching in B-lymphocytes and is therefore likely to be involved in situations where there is inappropriate IgE synthesis. Compounds of this invention inhibit the production of both IL-4 and IL-5 and can be expected to exhibit efficacy in atopic diseases where the aforementioned cytokines play a prominent role in disease pathophysiology. Summary of The Invention In its principle i embodiment, the present invention provides a compound represented by Formula I X 1T N— Q— E R N ' R5 I, or a pharmaceutically acceptable salt or prodrug thereof, where R l and R3 are : independently selected from (1) hydrogen, (2) aryl, (3) perfluoroalkyl of one to fifteen carbons, (4) halo, (5) -CN, (6) -NO 2 , (7) -OH, (8) -OG where G is a hydroxyl protecting group, (9) -CO2R6 where R6 is selected from (a) hydrogen, (b) cycloalkyl of three to twelve carbons, (c) aryl, (d) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, (ii) alkoxy of one to fifteen carbons, (iii) thioalkoxy of one to fifteen carbons, (iv) halo, (v) -NO 2 , and -2- (vi) -N 3 , (e) a carboxy protecting group, (f) alkyl of one to fifteen carbons, (g) alkyl of one to fifteen carbons substituted with 1, 2, or 3, or 4 substituents independently selected from (i) alkoxy of one to fifteen carbons, (ii) thioalkoxy of one to fifteen carbons, (iii) aryl, (iv) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from alkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, -NO2, and -N 3 , (v) cycloalkyl of three to twelve carbons, and (vi) halo, (h) alkenyl of three to fifteen carbons, provided that a carbon of a carbon-carbon double bond is not attached directly to oxygen, (i) alkynyl of three to fifteen carbons, provided that a carbon of a carbon-carbon triple bond is not attached directly to oxygen, and (j) cycloalkyl of three to twelve carbons, (10) -L1NR7R8 where Li is selected from (a) a covalent bond, (b) -X'C(X)- where X and X' are independently O or S, (c) -C(X)-, and (d) -NRδ- and R7 and Rs are independently selected from (a) hydrogen, (b) alkanoyl where the alkyl part is one to fifteen carbons, (c) alkoxycarbonyl where the alkyl part is one to fifteen carbons, (d) alkoxycarbonyl where the alkyl part is one to fifteen carbons and is substituted with 1 or 2 substituents selected from the group consisting of aryl, (e) cycloalkyl of three to twelve carbons, (f) aryl, (g) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, (ii) alkoxy of one to fifteen carbons, (iii) thioalkoxy of one to fifteen carbons, (iv) halo, (v) -NO 2 , and (vi) -N 3 , (h) -OR 6 , provided that only one of R 7 or Rs is -OR6, (i) a nitrogen protecting group, (j) alkyl of one to fifteen carbons, (k) alkyl of one to fifteen carbons substituted with 1, 2, or 3, or 4 substituents independently selected from (i) alkoxy of one to fifteen carbons, (ii) thioalkoxy of one to fifteen carbons, (iii) aryl, (iv) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from alkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, -NO 2 , and -N 3 , (v) cycloalkyl of three to fifteen carbons, (vi) halo, (vii) -CO 2 R6, and (viii) -OH, -4- (1) alkenyl of three to fifteen carbons, provided that a carbon of a carbon-carbon double bond is not attached directly to nitrogen, (m) alkynyl of three to fifteen carbons, provided that a carbon of a carbon-carbon triple bond is not attached directly to nitrogen, (n) -SO 2 -alkyl, and (o) cycloalkyl of three to twelve carbons, or R 7 and Rs together with the nitrogen atom to which they are attached form a ring selected from (i) aziridine, (ii) azetidine, (iii) pyrrolidine, (iv) piperidine, (v) piperazine, (vi) morpholine, (vii) thiomorpholine, and (viii) thiomorpholine sulfone where (i)-(viii) can be optionally substituted with 1 , 2, or 3 substituents selected from the group consisting of alkyl of one to fifteen carbons, (11) -L 2 Rα. where L 2 is selected from (a) -Li-, (b) -O-, and (c) -S(O) t - where t is 0, 1 , or 2 and R9 is selected from (a) cycloalkyl of three to twelve carbons, (b) aryl (c) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, (ii) alkoxy of one to fifteen carbons, (iii) thioalkoxy of one to fifteen carbons, (iv) halo, -5- (v) -NO 2 , and (vi) -N 3 , (d) alkyl of one to fifteen carbons, (e) heterocycle, (f) alkenyl of two to fifteen carbons, and (e) alkyl of one to fifteen carbons substituted with 1, 2, or 3, or 4 substituents independently selected from (i) alkenyl of two to fifteen carbons, (ii) alkoxy of one to fifteen carbons, (iii) -CN, (iv) -CO 2 R 6 , (v) -OH, provided that no two -OH groups are attached to the same carbon, (vi) thioalkoxy of one to fifteen carbons, (vii) alkynyl of two to fifteen carbons, (viii) aryl, (ix) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from alkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, -NO 2 , and -N 3 , (x) cycloalkyl of three to twelve carbons, and (xi) halo, (xii) -NR 7 R 8 , (xiii) heterocycle, and (xiv) heterocycle substituted with 1, 2, or 3, or 4 substituents independently selected from alkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, -6- halo, -NO 2 , and -N 3 , (12) alkyl of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 halo substituents, (13) alkyl of one to fifteen carbons, (14) alkenyl of two to fifteen carbons, (15) alkynyl of two to fifteen carbons where (13)-(15) can be optionally substituted with (a) (=X), (b) alkanoyloxy where the alkyl part is one to fifteen carbons, (c) alkoxy of one to fifteen carbons, (d) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo, (e) thioalkoxy of one to fifteen carbons, (f) perfluoroalkoxy of one to fifteen carbons, (g) -N 3 , (h) -NO 2 , (i) -CN, (j) "OH, (k) -OG (1) cycloalkyl of three to twelve carbons, (m) halo, (n) -CO 2 R 6 , (o) -LιNR 7 R 8 , and (p) -L 2 R 9 , (16) -L 2 -heterocycle, and (17) -L 2 -heterocycle where the heterocycle is substituted with 1, 2, 3 or 4 substituents independently selected from (a) alkyl of one to fifteen carbons, (b) perfluoroalkyl of one to fifteen carbons, (c) alkoxy of one to fifteen carbons, (d) thioalkoxy of one to fifteen carbons, (e) halo, and ( ) -NO 2 , (18) -NRχC(O)NRγRz where Rx, Ry and Rz are independently selected from (a) hydrogen and (b) alkyl of one to fifteen carbons, (19) -C(=NRχ)NRγR z , (20) -NRχC(=NRχ')NRγRz where Rx, Ry and Rz are defined previously and Rχ > is selected from (a) hydrogen and (b) alkyl of one to fifteen carbons, (21 ) -NRχC(O)OR y, where Rw is selected from (a) alkyl of one to fifteen carbons and (b) alkenyl of three to fifteen carbons, provided that a carbon of a carbon-carbon double bond is not attached directly to oxygen, and (22) -OC(O)NR 7 R 8 ; Z is nitrogen or carbon; R 2 is absent or is selected from (1) hydrogen, (2) -CO 2 R 6 , (3) alkyl of one to fifteen carbons, (4) -C(O)R6' where R6 1 is selected from (a) alkyl of one to fifteen carbons, (b) aryl, and (c) heterocycle, (5) -C(O)NR7'R8' where R7' and Rs 1 are independently selected from (a) hydrogen, (b) alkyl of one to fifteen carbons, or R7' and R 8 ' together with the nitrogen to which they are attached form a ring selected from (i) piperidine, (ii) piperazine, (iii) morpholine, (iv) thiomorpholine, and (v) thiomorpholine sulfone (6) perfluoroalkyl of one to fifteen carbons, (7) cycloalkyl of three to ten carbons, (8) alkyl of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group conststing of halo, (9) alkyl of one to fifteen carbons substituted with (a) -CN, (b) -OH, provided that no two -OH groups are attached to the same carbon, (c) (=X), and (d) -CO 2 R 6 , and (10) halogen; provided that when X is nitrogen, R 2 is absent; Q is aryl or heterocycle where, when Q is phenyl, the phenyl is 2-, 3-, or 4- substituted by E relative to the position of attachment of the pyrazole or 1,2,4-triazole ring to the phenyl ring; R4 and R5 are independently selected from (1) hydrogen, (2) alkyl of one to fifteen carbons, (3) alkyl of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 halo substituents, (4) alkyl of one to fifteen carbons substituted with (a) -CN, (b) -CO 2 R 6 , (c) -LιNR 7 Rs, and (d) -L 2 R 9 , (5) perfluoroalkyl of one to fifteen carbons, (6) -CN, (7) -CO 2 R 6 , (8) -L1NR7R0,, (9) -L 2 R 9 , (10) alkoxy of one to fifteen carbons, (11) thioalkoxy of one to fifteen carbons, (12) halo, (13) -C(=NR 6 )NR 7 R 8 , (14) -NRι 2 (=NR6)NR7R8 where Rβ, R7, and R 8 are defined previously and R 1 2 is selected from (a) hydrogen, (b) cycloalkyl of three to twelve carbons, (c) aryl, (d) alkyl of one to fifteen carbons, and (e) alkyl of one to fifteen carbons substituted with 1, 2, or 3, or 4 substituents independently selected from (i) alkenyl of two to fifteen carbons, (ii) alkoxy of one to fifteen carbons, (iii) thioalkoxy of one to fifteen carbons, (iv) alkynyl of two to fifteen carbons, and (v) aryl, (15) -L 2 -heterocycle, and (16) -L 2 -heterocycle where the heterocycle is substituted with 1, 2, 3, or 4 substituents independently selected from (a) alkyl of one to fifteen carbons, (b) perfluoroalkyl of one to fifteen carbons, (c) alkoxy of one to fifteen carbons, (d) thioalkoxy of one to fifteen carbons, (e) halo, (f) -N 3 , and (g) -NO 2 ; E is (1) -L -B where L 3 is selected from (a) a covalent bond, (b) alkenylene of two to six carbons in the Z or E configuration, (c) alkynylene of two to six carbons, (d) -C(X)-, (e) -N=N-, ( ) -NR7-, -10- (g) -N(R 7 )C(O)N(R 8 )-, (h) -N(R 7 )SO 2 N(R 8 )-, (i) -X-, (j) -(CH 2 ) m O-, (k) -O(CH 2 ) m -, (1) -N(R 7 )C(X)-, (m) -C(X)N(R 7 )-, (n) -S(O) t (CH 2 ) m -, (o) -(CH 2 )mS(O) r , (p) -NR 7 (CH 2 ) m -, (q) -(CH 2 ) m NR 7 -, (r) -NR 7 S(O)r, (s) -S(O) t NR 7 -, (t) -N=C(H)-, (u) -C(H)=N-, (v) -ON=CH-, (w) -CH=NO- where (g)-(w) are drawn with their left ends attached to Q, (x) -N(R7)C(O)N(Rιo)(Rι ι)- where Rio and R \ \ together with the nitrogen atom to which they are attached form a ring selected from (i) morpholine, (ii) thiomorpholine, (iii) thiomorpholine sulfone, and (iv) piperidine where (i)-(iv) are attached to Q through the nitrogen to which is attached R7 and to B through a carbon in the ring, (y) -N(R 7 )SO2N(Rio)(Ri i)-, and (z) -N(R 7 )C(O)N(R 10 )(Rπ)- and B is selected from (a) alkyl of one to fifteen carbons, (b) alkenyl of three to fifteen carbons in the E or Z configuration, provided that a carbon of a carbon-carbon double bond is not directly attached to L3 when L 3 is other than a covalent bond, (c) alkynyl of three to fifteen carbons, -11- provided that a carbon of a carbon-carbon triple bond is not directly attached to L 3 when L 3 is other than a covalent bond where (a), (b) and (c), can be optionally substituted with 1, 2, 3, or 4 substituents independently selected from B R A- — J^Rc (i) R E where L 2 is defined previously and RA, RB > Rc, RD > and RE are independently selected from hydrogen, alkanoyl where the alkyl part is one to fifteen carbons, alkanoyloxy where the alkyl part is one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo , perfluoroalkyl of one to fifteen carbons, perfluoroalkoxy of one to fifteen carbons, -N 3 , -NO 2 , -CN, -OH, -OG, cycloalkyl of three to fifteen carbons, halo, -CO 2 R 6 -LιNR 7 R 8 -L 2 R 9 alkyl of one to fifteen carbons, alkyl of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents independently selected from (=X), -12- alkanoyloxy where the alkyl part is one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, 5 alkoxy of one to fifteen carbons substituted with 1, 2, 3,4, or 5 halo substituents, perfluoroalkoxy of one to fifteen carbons, -N 3 , -NO 2 , 10 -CN, -OH, provided that no two -OH groups are attached to the same carbon, -OG, 15 cycloalkyl of three to fifteen carbons, halo, -CO 2 R 6 , -LιNR 7 R 8 , and -L 2 R 9 , 20 -L 2 -heterocycle, and -L 2 -heterocycle where the heterocycle is substituted with 1, 2, 3, or 4 substituents independently selected from 25 alkyl of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, 30 -NRχC(O)NR γ R z , -C(=NRX)RγR z , -NO 2 , and -N 3 , (ii) (=X) -13- (iii) alkanoyloxy where the alkyl part is one to fifteen carbons, (iv) alkoxy of one to fifteen carbons, (v) alkoxy of one to fifteen carbons substituted with 1 , 2, 3, 4, or 5 substituents selected from the group consisting of halo, 5 (vi) thioalkoxy of one to fifteen carbons, (vii) perfluoroalkoxy of one to fifteen carbons, (viii) -N 3 , (ix) -NO 2 , (x) -CN, 10 (xi) -OH, provided that no two -OH groups are attached to the same carbon, (xii) -OG, (xiii) cycloalkyl of three to fifteen carbons, 15 (xiv) halo, (xv) -CO 2 R 6 , (xvi) -L!NR 7 R 8 , (xvii) perfluoroalkyl of one to fifteen carbons, (xviii) -L 2 -heterocycle, and 20 (xix) -L 2 -heterocycle where the heterocycle is substituted with 1 , 2, 3, or 4 substituents independently selected from (=X), alkanoyl where the alkyl part is one to fifteen carbons, alkanoyloxy where the alkyl part is one to fifteen 25 carbons, alkoxy of one to fifteen carbons, alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo , 30 thioalkoxy of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, perfluoroalkoxy of one to fifteen carbons, -N 3 , -NO 2 , -14- -CN, -OH, provided that no two -OH groups are attached to the same carbon, -OG, cycloalkyl of three to fifteen carbons, halo, -CO 2 R 6 , -LιNR 7 Rs, and -L 2 R 9 , (d) cycloalkyl of three to twelve carbons, (e) cycloalkenyl of four to twelve carbons, provided that a carbon of a carbon-carbon-double bond is not attached directly to L 3 when L 3 is other than a covalent bond where (d) and (e) can be optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, (ϋ) aryl, - (iii) alkoxy of one to fifteen carbons, (iv) thioalkoxy of one to fifteen carbons, (v) halo, (vi) -OH, provided that no two -OH groups are attached to the same carbon, (vii) oxo, (viii) perfluoroalkyl, (ix) heterocycle, and (x) heterocycle substituted with 1, 2, 3, 4, or 5 substituents independently selected from alkyl of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, -15- -NO 2 , and -N 3 , R c (f) R E provided that when Rj and R 3 are both perfluoroalkyl of one carbon, Z is carbon, R 2 is hydrogen, Q is phenyl that is 4-substituted by E relative to the position of attachment of the pyrazole ring to the phenyl group, R4 and R5 are hydrogen, E is -L3-B, L is -N(R7)C(X)-, R7 is hydrogen, X is oxygen, and RA, RB, RD > and RE are hydrogen, Re is other than chloro, and (g) heterocycle where the heterocycle can be optionally substituted with 1 , 2, 3, or 4 substituents independently selected from (i) (=X), (ii) alkanoyl where the alkyl part is one to fifteen carbons, (iii) alkanoyloxy where the alkyl part is one to fifteen carbons, (iv) alkoxy of one to fifteen carbons, (v) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo, (vi) halo , (vii) thioalkoxy of one to fifteen carbons, (viii) perfluoroalkyl of one to fifteen carbons, (ix) perfluoroalkoxy of one to fifteen carbons, (x) -N 3 , (xi) -NO 2 , (xii) -CN, (xiii) -OH, provided that no two -OH groups are attached to the same carbon, (xiv) -OG, (xv) cycloalkyl of three to fifteen carbons, -16- (xvi) halo, (xvii) -CO 2 R 6 , (xviii) alkyl optionally substituted with -OH, (xix) -L 1 NR 7 R0,, and (xx) -L 2 R 9 , and O -Rl3 R i (2) O where Ri 3 and R14 are independently selected from (a) hydrogen, (b) alkyl of one to fifteen carbons, (c) alkenyl of three to fifteen carbons in the E or Z configuration, provided that a carbon of a carbon-carbon double bond is not attached directly to the C(=O) group, (d) alkynyl of three to fifteen carbons, provided that a a carbon-carbon triple bond is not directly attached to the C(=O) group where (b), (c), and (d) can be optionally substituted with 1, 2, 3, or 4 substituents independently selected from R B R D (i) RE (ϋ) (=X), (iii) alkanoyloxy where the alkyl part is one to fifteen carbons, (iv) alkoxy of one to fifteen carbons, (v) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo, (vi) thioalkoxy of one to fifteen carbons, (vii) perfluoroalkoxy of one to fifteen carbons, (Viii) -N 3 , (ix) -NO2, (x) -CN, (xi) -OH, -17- provided that no two -OH groups are attached to the same carbon, (xii) -OG, (xiii) cycloalkyl of three to fifteen carbons, (xiv) halo, (xv) -CO 2 R 6 , (xvi) -LιNR 7 R 8 , (xvii) perfluoroalkyl of one to fifteen carbons, (xviii) -L 2 -heterocycle, and (xix) -L 2 -heterocycle where the heterocycle is substituted with 1, 2, 3, or 4 substituents independently selected from (=X), alkanoyl where the alkyl part is one to fifteen carbons, alkanoyloxy where the alkyl part is one to fifteen carbons, alkoxy of one to fifteen carbons, alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo, thioalkoxy of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, perfluoroalkoxy of one to fifteen carbons, -N 3 , -NO 2 , -CN, -OH, provided that no two -OH groups are attached to the same carbon, -OG, cycloalkyl of three to fifteen carbons, halo, -CO 2 R 6 , -LιNR 7 R 8 , -L 2 R 9 , (e) cycloalkyl of three to twelve carbons, -18- (f) cycloalkenyl of four to twelve carbons, provided that a carbon of a carbon-carbon double bond is not attached directly to the C(=O) group where (e) and (f) can be optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, (ii) aryl, (iii) alkoxy of one to fifteen carbons, (iv) thioalkoxy of one to fifteen carbons, (v) halo, (vi) -OH, provided that no two -OH groups are attached to the same carbon, (vii) heterocycle, and (viii) heterocycle substituted with 1, 2, 3, 4, or 5 substituents independently selected from alkyl of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, -NO 2 , and -N 3 , (g) heterocycle, and (h) heterocycle substituted with 1, 2, 3, or 4 substituents independently selected from (i) (=X), (ii) alkanoyl where the alkyl part is one to fifteen carbons, (iii) alkanoyloxy where the alkyl part is one to fifteen carbons, (iv) alkoxy of one to fifteen carbons, (v) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo, -19- (vi) thioalkoxy of one to fifteen carbons, (vii) perfluoroalkyl of one to fifteen carbons, (viii) perfluoroalkoxy of one to fifteen carbons, (ix) -N 3 , (x) -NO 2 , (xi) -CN, (xϋ) -OH, provided that no two -OH groups are attached to the same carbon, (xiϋ) -OG, (xiv) cycloalkyl of three to fifteen carbons, (xv) halo, (xvi) -CO 2 R 6 , (xvii) -LιNR 7 R 8 , (xviii) -L 2 R 9 , rovided that at least one of Rι 3 and R 1 4 is other than hydrogen, or 1 3 and R 1 4 together with the nitrogen to which they are attached form a ring selected from (a) succinimidyl, (b) maleimidyl, (c) glutarimidyl, (d) phthalimidyl, naphthalimidyl, (f) 0 I 1 N H 3 C N ^( (g) O H 3 C^K (h) -20- (i) Ci) (k) (1) (m) where (a)-(m) can be optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo and -L 2 R 9 . In another embodiment, the present invention also relates to a method of inhibiting Interleukin-2, Interleukin-4, and Interleukin-5 production in a mammal comprising administering a therapeutically effective amount of a compound of Formula I. In yet another embodiment, the present invention also relates to a method of treating immunologically-mediated diseases in a mammal comprising administering a therapeutically effective amount of a compound of Formula I. In still yet another embodiment, the present invention relates to pharmaceutical compositions which comprise a therapeutically effective amount of a compound of Formula I in combination with a pharmaceutically acceptable carrier. Compounds of the invention include but are not limited to N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]cycloproρanecarboxamide, -21- N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,2,3,3- tetramethylcyclopropane-carboxamide, N- [4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-2,2-dichloro- 1 - methylcyclopropanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-oxo-6-pentyl-2H-pyran-3- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3,5- difluorobenzenesulfonamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l-cyclohexene-l- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2- methylcyclopropanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-(3,5-dichlorophenoxy)-2- furancarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] - 1 -methyl-2-cyclohexene- 1 - carboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] - 1 -cyclopentene- 1 - carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-methoxycyclohexane- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-butynamide, ethyl 3-[[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]amino]carbonyl]- amino]benzoate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-methyl-3-nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-(3-cyanophenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l- hydroxycyclopropanecarboxamide, N-[4[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]cycloheptanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-benzofurancarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] -5-fluoro- 1 H-indole-2- carboxamide, (E)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-(2-chlorophenyl)-2- propenamide, -22- 2-benzoyl-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, 3a(S)-(3aα,4β,6aα)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l- yl]phenyl]hexahydro-2-oxo-lH-thieno[3,4-d]imidazole-4-pentanamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-iodobenzamide, exo-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]bicyclo[2.2.1]hept-5-ene- 2-carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-methylcyclohexane- carboxamide, phenylmethyl [ 1 - [[ [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] amino] - carbonyl]propyl]carbamate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-cyclohexene-l- carboxamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-N-(4-fluorophenyl)benzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-N'-(3 -nitrophenyl)urea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] -N'-(4-fluorophenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-[4-(trifluoromethyl)- phenyljurea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-(3,5-dimethylphenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l- methylcyclopropanecarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-N'-phenylurea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-(3-chloro-2- methylphenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-[4-(butyloxyphenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-(2-methyl-3- nitrophenyl)urea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-N'-(2-chloro-4- nitrophenyl)urea, N-(4-acetylphenyl)-N'-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-n'-(4-methyl-2- nitrophenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-methyl-2-thiophene- carboxamide, -23- N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-(4-bromo-2,6-dimethyl- phenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-(lH-pyrrol-l-yl)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-heptylurea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-(4-chloro-2-nitro- phenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-7-methoxy-2- benzofurancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-2-methyl-5-nitrophen- yl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-(hydroxymethyl)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-cyanoacetamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-cyclohexane-l- carboxamide, N- [4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-4- methylcyclohexanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-α-methoxy-α- (trifluoromethyl)benzeneacetamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]heptanamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-phenoxybenzamide, 3-amino-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, 4-amino-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, 4-azido-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-2-thiopheneacetamide, N-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l-tricyclo[3.3.1.1 3 ' 7 ]decane- carboxmide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-N 2 - [( 1 , 1 -dimethylethoxy)- carbonyl]-l-asparagine, phenylmethyl ester, 1,1-dimethylethyl [7-[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]amino]-7- oxoheptyljcarbamate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-(methylthio)propanamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l-naphthylenecarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] -4-cy anobenzamide, -24- N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] -2-phenylcyclopropane- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-4-iodobenzamide. N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-3-chloropropan amide, N-[4-[3,5-bis(trifιuoromethyl)-lH-pyrazol- -yl]phenyl]-4-methoxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2-ethylhexanamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-4-hydroxybenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-4-(hexyloxy)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-3-methylbenzamide, 2-(acetyloxy)-N-[4-[3,5-bis(trifluoromethyl -1 H-pyrazol- l-yl]phenyl]benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl] -N'-(4-bromo-2- methy lpheny 1) urea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2,4,6-trimethylbenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-N'-(4-chloro-3- nitropheny 1) urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2-chloro-N-methylbenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2-chloro-4-nitro-N- methylbenzamide, N- [4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2- chlorobenzenemethanamine, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yljphenyl]- 1 -methyl-5-nitro- 1 H-pyra- zole-4-carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-4-fluorobenzenemethanamine, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-4-bromobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2-(dimethylamino)benzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-3-(dimethylamino)benzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-4-(trifluoromethyl)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl phenyl] -4-fluorobenzamide , N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2-chlorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-4-nitrobenzamide, 4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -y |-N-(4-fluorophenyl)benzenemethanamine, 3-[4-[[[3,5-bis(trifluoromethyl)- IH-pyrazol l-yl]phenyl]methyl]amino]benzonitrile, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-2-methylbenzamide, -25- (E)-N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenylmethylene] -2 ,4-difluoro benzenamine, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3-4-dimethoxybenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]cyclopentanepropanamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-methylbenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3-(trifluoromethyl)benzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3-methyl-2-butenamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2-hydroxybenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3-hydroxybenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,4-dimethyl-5- thiazolecarboxamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3-pyridinecarboxamide, N-[4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-(hydroxymethyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH- pyrazol-1-y -N-(2,4- difluorophenyl)benzenemethanamine, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-(methylsulfonyl)benzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2-iodobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-heptybenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2-furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2-fluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]ρhenyl]-N'-methyl- 1 ,2- benzenedicarboxamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-chloro-2-nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-cinnolinecarboxamide, 4-acetyl-N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]benzamide, 1,1-dimethylethyl 4-[[[4-[3,5-b s(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]- aminojcarbonyl]- 1 -piperidinecarboxylate, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- 1 -yl]phenyl]-2-pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- 1 -yl]phenyl]-4-(diethylamino)benzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- 1 -yl]phenyl]cyclopentanecarboxmide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- 1 -yl]phenyl]cyclohexanecarboxmide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- 1 -yl]phenyl]-4-piperidinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- 1 -yl]phenyl]-3-(methylsulfonyl)benzamide, -26- N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-(trifluoromethyl)benzamide, 3-[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]methyl]amino]benzonitrile, methyl 3-[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l- yl]phenyl]amino]carbonyl]benzoate, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]-3-chlorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-thiophenecarboxamide, (E)-3-[2-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]ethenyl]benzonitrile, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yljphenyl]- 1 ,4-benzenedicarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]ρhenyl]-3,5-dinitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]-2,4-difluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]ρhenyl]-2-nitrobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] -3-cy anobenzamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l,3-benzenedicarboxamide, (Z)-3-[2-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]ethenyl]benzonitrile, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-nitrobenzamide, 3-(aminosulfonyl)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, methyl 4- [[ [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 - yl]phenyl]amino]carbonyl]benzoate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-methoxybenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-bromobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-methoxybenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-fluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] -2-bromobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l,3-benzodioxole-5- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,6-dichloro-3- pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-chloro-3- pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-chloro-6-methyl-3-pyridine- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-fluoro-γ- oxobenzenebutan amide, -27- N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]- 1 ,2,3,4-tetrahydro-2- naphthalenecarboxamide, (E)-l-[4-[2-(2-chlorophenyl)ethenyl]phenyl]-3,5-bis(trifluoromethyl)-lH-pyrazole, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] -2-(4-chlorophenoxy )-2- methylpropanamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]acetamide, 4-[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]amino]carbonyl]benzoic acid, phenylmethyl N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]pheny 1] amino] -4- oxobutyljcarbamate, 3-[[[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]amino]carbonyl]benzoic acid, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,6-difluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-bromo-2- thiophenecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-methyl-2- thiophenecarboxamide, 2-amino-N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-fluoro-3- pyridinecarboxamide, N- [4- [3, 5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl] -3-chloro-4-(methylsulfonyl)- 2-thiophenecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-lH-pyrrole-2-carboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-3 ,6-dichloro-2- pyridinecarboxamide N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-(2-nitrophenoxy)acetamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-chlorobenzeneacetamide, N-[4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl]- 1 H-indole-2-acetamide, (E)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-(2-thienyl)-2- propenamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]pyazinecarboxamide, 1 ,1-dimethylethyl [[4-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]amino]-4- oxobuty 1] carbamate , l-acetyl-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4- piperidinecarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]butanamide, -28- N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-4-chloro-2- methoxybenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-α-methyl-4-(2-thienyl- carbonyl)benzeneacetamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] -α-methyl-4-(2-thienyl carbonyl)benzeneacetamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]-2-methoxy-4- (methy thio)benzamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-hydroxy-3-nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenylj-3,4-dihydroxybenzamide, N- [4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-2-hydroxy-6- methoxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] -2,4- bis(trifluoromethyl)benzamide, N- [4- [3 , 5 -bis (trifluoromethy 1)- 1 H-pyrazol- 1 -y 1] phenyl] -5 -methy 1-4- isoxazolecarboxamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]-N-(2-chlorophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]-N-(3-cyanophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l -yl]-N-(2,4-difluorophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l -yl]-N-(2-cyanophenyl)benzamide, N-[4-[5-[3,5-dimethyl-lH-l,2,4-triazol- -yl)-3-(trifluoromethyl)- 1 H-pyrazol- 1 - yl]phenyl]-4-isoxazolecarboxamide, 4- [3, 5-bis(trifluoromethyl)-l H-pyrazol- 1 -yl]-N-(2-nitrophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]-N-(2,6-difluorophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l -yl]-N-(2-bromophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l -yl]-N-(4-cyanophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]-N-(4-pyridinyl)benzamide, N- [4- [3, 5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-4-fluoro-3-(trifluorometh- yl)benzamide, N- [2-(aminocarbonyl)phenyl] -4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljbenzamide, N-[3-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-chlorobenzeneacetamide, N-[3-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,3-dichlorobenzamide, N-[3-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-chloro-5-nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-fluoro-3-nitrobenzamide, -29- N- [4- [3 , 5 -bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-fluoro-3-nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-fluoro-2-(trifluoromethyl)- benzamide, N-[3-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-fluorobenzamide, N-[3-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,4-difluorobenzamide, N-[3-[3,5-bis(trifluoromethyl)- H-pyrazol- -yljphenyl] -3-cyanobenzamide , N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yljphenyl]-2-bromo-3-nitrobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2-chloro-4-fluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2-chloro-4-(methylsulfonyl)- benzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,5-dichlorobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,3-difluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3-chloro-4-fluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,5-difluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2-chloro-6-fluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2-fluoro-6-(trifluoromethyl)- benzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3-chloro-2-fluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2-chloro-4- methoxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,6-dichloro-3- nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-bromo-2-chlorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3,4-difluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl] -2-bromo-5 - methoxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-chloro-2- hydroxybenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3-bromo-4- methoxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3-bromo-4- hydroxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2-chloro-4,5- difluorobenzamide, -30- N-[3-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,6-difluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-chloro-2,5- difluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,3,4-trifluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]-3,4,5-trifluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,4,5-trifluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,4,6-trifluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,6-difluoro-3- nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,3,5-trifluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,4-dichloro-6- fluorobenzamide, N-4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl-2,4-dichloro-3,5- dinitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,3,5,6-tetrafluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,3,4,5-tetrafluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-bromo-2,3,5,6- tetrafluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-methyl-2-nitrobenzamide, N- [3- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl] -4-cyanobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-thiophenecarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-5-isoxazolecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]tetrahydro-2- furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-2-pyrrolidinecarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl] tetrahydro-3- furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l,2,3-thiadiazole-5- carboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]-2-chloro-4- pyridinecarboxamide, 1 , 1-dimethylethyl 2- [[[4- [3, 5-bis(trifluoromethyl)- IH-pyrazol- 1 - yl]phenyl]amino]carbonyl]-l-pyrrolidinecarboxylate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-nitro-2-furancarboxamide, -31- N- [4- [3, 5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl]- 1 -methyl- lH-pyrrole-2- carboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]-6-chloro-3- pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-bromo-2-furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-methyl-2- furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-chloro-2- thiophenecarboxamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]tetrahydro-5-oxo-2-furan- carboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]-5-oxo-2- pyrrolidinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]-5-bromo-3- pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-nitro-3-thiophenecar- boxamide, 1,1-dimethylethyl 4-[[[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]amino]- carbonyl]-3-thiazolidinecarboxylate, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]-5-methoxy-3- thiophenecarboxamide, N-[2-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-5-pyridinyl]-2-chlorobenzamide, N-[2-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-5-pyridinyl]-3-cyanobenzamide, N-[2-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-5-pyridinyl]-2-chloro-4,5- difluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,3-dibromo-5- thiophenecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-fluoro-4-pyridine- carboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]- 1 -methyl- lH-pyrazole-4- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-chloro-4-methoxy-3- thiophenecarboxamide, -32- N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5,6-dichloro-3- pyridinecarboxamide N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,6-dichloro-4- pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,5-dichloro-3- pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]-3-(trifluoromethyl)phenyl]-4- chlorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-2-fluorophenyl]-2,4- difluorobenzamide, N-[2,4-bis[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,4-difluorobenzamide, methyl 2-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-5-[(5-bromo-2- chlorobenzoyl)amino]benzoate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-3-(trifluoromethyl)phenyl]-3,5- dimethyl-4-isoxazolecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-3-(trifluoromethyl)phenyl]-4-methyl- 1 ,2,3-thiadiazole-5-carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-3-chlorophenyl]-3,5-dimethyl-4- isoxazolecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-2-(trifluoromethyl)phenyl]-3,5- dimethyl-4-isoxazolecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-2-methylphenyl]-4-methyl-l,2,3- thiadiazole-5-carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-2-methoxyphenyl]-4-methyl- 1,2,3- thiadiazole-5-carboxamide, 4-chloro-N-[4-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, 4-methyl-N-[4-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l,2,3- thiadiazole-5-carboxamide, 3,5-dimethyl-N-[4-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4- isoxazolecarboxamide, 4-chloro-N-[4-(5-methyl- IH-pyrazol- 1 -yl)phenyl]benzamide, 4-methyl-N-[4-(5-methyl-lH-pyrazol-l-yl)phenyl]-l,2,3-thiadiazole-5-carboxamide, 3,5-dimethyl-N-[4-(5-methyl-lH-pyrazol-l-yl)phenyl]-4-isoxazolecarboxamide, -33- 3,5-dimethyl-N-[4-[3-(trifluoromethyl)- IH-pyrazol- l-yl)phenyl]-4- isoxazolecarboxamide, N-[4-[5-hydroxy-3-(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-methyl- 1,2,3- thiadiazole-5-carboxamide, N-[4-[5-(3,5-dimethyl- 1H- 1 ,2,4-triazol- 1 -yl)-3-(trifluoromethyl)- IH-pyrazol- 1 - yl]phenyl]- 1 ,2,3-thiadiazole-5-carboxamide, 3-amino-N-(4-(3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)isonicotinamide, N-(4-(3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl)phenyl)-3-chloro-5- methoxyisonicotinamide, N-(6-(3,5-bis(trifluoromethyl)-l H-pyrazol- l-yl)-3-pyridinyl)-2-fluorobenzamide, methyl 2-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)-5-((2- fluorobenzoyl)amino)benzoate, 4-(aminomethyl)-N-(4-(3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl)phenyl)-2- chlorobenzamide, N-(4-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2-methylacrylamide, N-(4-(3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-4-chloro-2-fluorobenzamide, N-(5-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)-2-pyridinyl)-2-fluorobenzamide, N-(3-amino-4-(3,5-bis(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-2-fluorobenzamide, N-(4-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)-3-cyanophenyl)-2-fluorobenzamide, N-(4-(5-cyano-3-(trifluoromethyl)- IH-pyrazol- l-yl)phenyl)-2-fluorobenzamide, 2-fluoro-N-(4-(5-(2-furyl)-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)benzamide, N-(4-(5-cyano-3-(trifluoromethyl)- IH-pyrazol- l-yl)phenyl)-4-methyl- 1,2,3- thiadiazole-5-carboxamide, N-(4-(5-cyano-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)isonicotinamide, N-(4-(5-cyano-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-3-fluoroisonicotinamide, N-(4-(5-acetyl-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-2-fluorobenzamide, N-(4-(5-cyano-3-(trifluoromethyl)-l H-pyrazol- l-yl)ρhenyl)-2-fluoronicotinamide, N-(4-(5-cyano-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-2,3,5-trifluorobenzamide, 2-fluoro-N-(4-(5-(2-thienyl)-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)benzamide, 2-fluoro-N-(4-(5-(methylsulfanyl)-3-(trifluoromethyl)- IH-pyrazol- 1- yl)phenyl)benzamide, 2-fluoro-N-(4-(5-(3-pyridinyl)-3-(trifluoromethyl)-lH-pyrazol-l- yl)phenyl)benzamide, -34- 3-fluoro-N-(4-(5-(2-thienyl)-3-(trifluoromethyl)- IH-pyrazol- 1- yl)phenyl)isonicotinamide, N-(4-(5-methoxy-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)isonicotinamide, 2-fluoro-N-(4-(5-methoxy-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)benzamide, N-(4-(5-methoxy-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-4-methyl- 1 ,2,3- thiadiazole-5-carboxamide, N-(4-(5-acetyl-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-2-fluoronicotinamide, 2-fluoro-N-(4-(5-(methylsulfanyl)-3-(trifluoromethyl)- IH-pyrazol- 1- yl)phenyl)nicotinamide, 2-fluoro-N-(4-(5-methoxy-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)nicotinamide, N-(4-(5-ethoxy-3-(trifluoromethyl)- IH-pyrazol- l-yl)phenyl)-2-fluoronicotinamide, 3-fluoro-N-(4-(5-(methylsulfanyl)-3-(trifluoromethyl)- IH-pyrazol- 1- yl)phenyl)isonicotinamide, 3-fluoro-N-(4-(5-methoxy-3-(trifluoromethyl)- IH-pyrazol- 1 - yl)phenyl)isonicotinamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- IH-pyrazol- 1 - yl)phenyl)isonicotinamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-4-methyl- l,2,3-thiadiazole-5-carboxamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- IH-pyrazol- l-yl)phenyl)-2- fluoronicotinamide, N-(4-(5-chloro-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-2-fluoronicotinamide, 2-fluoro-N-(4-(5-nitro-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)benzamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-chloro-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-3-fluoroisonicotinamide, N-(4-(5-bromo-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-3-fluoroisonicotinamide, 3-fluoro-N-(4-(5-nitro-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)isonicotinamide, N-(4-(5-bromo-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-4-methyl-l,2,3-thiadiazole- 5-carboxamide, N-(4-(5-chloro-3-(trifluoromethyl)-lH-l,2,4-triazol-l-yl)phenyl)-3- fluoroisonicotinamide, 3-fluoro-N-(4-(5-(l -methyl- lH-pyrrol-3-yl)-3-(trifluoromethyl)- IH-pyrazol- 1- yl)phenyl)isonicotinamide, -35- 3-chloro-N-(4-(5-chloro-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)isonicotinamide, N-(4-(5-bromo-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-2,3-difluorobenzamide, N-(4-(5-bromo-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-3-chloroisonicotinamide, 2-chloro-N-(4-(5-cyano-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)benzamide, 3-chloro-N-(4-(5-cyano-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)isonicotinamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2- fluorobenzamide, 2-chloro-N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- 1 H-pyrazol- 1 - yl)phenyl)benzamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- IH-pyrazol- l-yl)phenyl)-2,3- difluorobenzamide, 3-fluoro-N-(4-(3-(4-pyridinyl)-5-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)isonicotinamide, N-(4-(5-(difluoromethyl)-3-(3-pyridinyl)- IH-pyrazol- l-yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-cyano-3-(2-pyridinyl)- 1 H-pyrazol- 1 -yl)phenyl)-3-fluoroisonicotinamide, N-(4-(5-cyano-3-(3-pyridinyl)-lH-pyrazol-l-yl)phenyl)-4-methyl-l,2,3-thiadiazole-5- carboxamide, 3-fluoro-N-(4-(5-nitro-3-(3-pyridinyl)- IH-pyrazol- 1 -yl)phenyl)isonicotinamide, 4-methyl-N-(4-(5-nitro-3-(3-pyridinyl)-lH-pyrazol-l-yl)phenyl)-l,2,3-thiadiazole-5- carboxamide, N-(4-(5-cyano-3-(l,3-thiazol-2-yl)- IH-pyrazol- l-yl)phenyl)-3-fluoroisonicotinamide, N-(4-(3-(5-bromo-3-pyridinyl)-5-(difluoromethoxy)- IH-pyrazol- l-yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-cyano-3-( 1 ,3-thiazol-2-yl)- IH-pyrazol- 1 -yl)phenyl)-4-methyl- 1 ,2,3- thiadiazole-5-carboxamide, N-(4-(5-cyano-3-( 1 ,3-thiazol-2-yl)- 1 H-pyrazol- 1 -yl)phenyl)-3-fluoroisonicotinamide, 4-methyl-N-(4-(3-( 1 ,3-thiazol-2-yl)-5-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)- 1 ,2,3-thiadiazole-5-carboxamide, N-(4-(3-(2,4-dimethyl- 1 ,3-thiazol-5-yl)-5-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-3- fluoroisonicotinamide, 3-fluoro-N-(4-(3-tetrahydro-2-furanyl-5-(trifluoromethyl)- 1 H-pyrazol- 1 - yl)phenyl)isonicotinamide, N-(4-(5-chloro-3-(l,3-thiazol-2-yl)-l H-pyrazol- l-yl)phenyl)-3-fluoroisonicotinamide, -36- N-(4-(5-chloro-3-(3-furyl)- IH-pyrazol- l-yl)phenyl)-4-methyl-l,2,3-thiadiazole-5- carboxamide, N-(4-(5-chloro-3-(3-furyl)-l H-pyrazol- l-yl)phenyl)-3-fluoroisonicotinamide, N-(4-(5-cyano-3-tetrahydro-2-furanyl-l H-pyrazol- l-yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-(difluoromethoxy)-3-(l -methyl- lH-pyrrol-3-yl)- IH-pyrazol- l-yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-(difluoromethoxy)-3-(3-furyl)-lH-pyrazol-l-yl)phenyl)-3- fluoroisonicotinamide, and N-(4-(5-(difluoromethoxy)-3-( 1 -methyl- 1 H-pyrrol-2-yl)- 1 H-pyrazol- 1 -yl)phenyl)-3 - fluoroisonicotinamide. Detailed Description of the Invention Definition of Terms The term "alkanoyl" refers to an alkyl group attached to the parent molecular group through a carbonyl group. The term "alkanoyloxy" refers to an alkanoyl group attached to the parent molecular group through an oxygen atom. The term "alkenyl" refers to a monovalent straight or branched chain group derived from a hydrocarbon of two to fifteen carbons having at least one carbon-carbon double bond. The alkenyl groups of this invention can be optionally substituted. The term "alkenylene" refers to a divalent straight or branched chain group derived from a hydrocarbon of two to fifteen carbons having at least one carbon-carbon double bond. The term "alkoxy" refers to an alkyl group attached to the parent molecular group through an oxygen atom. The term "alkyl" refers to a monovalent straight or branched chain group derived from an saturated hydrocarbon of one to fifteen carbons. The alkyl groups of this invention can be optionally substituted. The term "alkylene" refers to a divalent group derived from a straight or branched chain saturated hydrocarbon of one to fifteen carbons. The term "alkynyl" refers to a monovalent straight or branched chain group derived from a hydrocarbon of one to fifteen carbons having at least one carbon-carbon triple bond. The alkynyl groups of this invention can be optionally substituted. The term "alkynylene" refers to a divalent group derived from a straight or branched -37- chain hydrocarbon of one to fifteen carbons having at least one carbon-carbon triple bond. The term "amino" refers to -NH 2 . The term "amino protecting group" refers to groups intended to protect an amino group against undersirable reactions during synthetic procedures. Commonly used amino protecting groups are disclosed in Greene, "Protective Groups In Organic Synthesis," (John Wiley & Sons, New York (1981)), which is hereby incoφorated by reference. Preferred N- protecting groups are formyl, acetyl, benzoyl, pivaloyl, t-butylacetyl, phenylsulfonyl, benzyl, t-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), and allylcarbonyloxy (Alloc). The term "aryl" refers to a mono- or bicyclic carbocyclic ring system having at least one aromatic ring that can be optionally substituted. The aryl group can be fused to a cyclohexane, cyclohexene, cyclopentane or cyclopentene ring in which case the aryl group can be attached through the ring to which it is attached or through the aromatic ring itself. The term "carboxy protecting group" refers to a carboxylic acid protecting ester or amide group typically employed to block or protect the carboxylic acid functionality while the reactions involving other functional sites of the compound are performed. Carboxy protecting groups are disclosed in Greene, "Protective Groups in Organic Synthesis". Additionally, a carboxy protecting group can be used as a prodrug whereby the carboxy protecting group can be readily cleaved in vivo, for example by enzymatic hydrolysis, to release the biologically active parent. Such carboxy protecting groups are well-known to those skilled in the art, having been extensively used in the protection of carboxyl groups in the penicillin and cephalosporin fields as described in U.S. Pat. Nos. 3,840,556 and 3,719,667 which are hereby incoφorated by reference. The term "cycloalkenyl" refers to a monovalent cyclic or bicyclic hydrocarbon of three to fifteen carbons having at least one carbon-carbon double bond. The cycloalkenyl groups of this invention can be optionally substituted. The term "cycloalkyl" refers to a monovalent saturated cyclic or bicyclic hydrocarbon of three to fifteen carbons. The cycloalkyl groups of this invention can be optionally substituted. The term "halo" refers to F, CI, Br, or I. The terms "heterocycle," or "heterocyclic" refer to a 4-, 5-, 6- or 7-membered ring containing one, two or three heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur. The 4- and 5-membered rings have 0, 1 , or 2 double bonds and the 6- and 7-membered rings have 0, 1, 2, or 3 double bonds. The nitrogen and sulfur atoms can be optionally oxidized, and the nitrogen atom can be optionally quaternized. The term -38- "heterocycle" also includes bicyclic, tricyclic, and tetracyclic groups in which a heterocyclic ring is fused to one or two rings selected from an aryl ring, a cyclohexane ring, a cyclohexene ring, a cyclopentane ring, a cyclopentene ring or another monocyclic heterocyclic ring. Heterocycles of this type can be attached through the ring to which they are fused or through the heterocyclic ring itself. Heterocycles include, but are not limited to, acridinyl, benzimidazolyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, biotinyl, cinnolinyl, dihydrofuryl, dihydroindolyl, dihydropyranyl, dihydrothienyl, dithiazolyl, furyl, homopiperidinyl, imidazolidinyl, imidazolinyl, imidazolyl, indolyl, isoquinolyl, isothiazolidinyl, isothiazolyl, isoxazolidinyl, isoxazolyl, moφholinyl, oxadiazolyl, oxazolidinyl, oxazolyl, piperazinyl, piperidinyl, pyranyl, pyrazolidinyl, pyrazinyl, pyrazolyl, pyrazolinyl, pyridazinyl, pyridyl, pyrimidinyl, pyrimidyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinolinyl, quinoxaloyl, tetrahydrofuryl, tetrahydroisoquinolyl, tetrahydroquinolyl, tetrazolyl, thiadiazolyl, thiazolidinyl, thiazolyl, thienyl, thiomoφholinyl, triazolyl, and the like. Heterocyclics also include bridged bicyclic groups where a monocyclic heterocyclic group is bridged by an alkylene group such as H ® N H and the like. Heterocyclics also include compounds of the formula Y* ° where X* is selected from -CH 2 -, -CH 2 O- and -O-,and Y* is selected from -C(O)- and -(C(R") 2 ) V -, where R" is hydrogen or alkyl of one to four carbons and v is 1, 2, or 3. The heterocycles of this invention can be optionally substituted. The term "hydroxyl" refers to -OH. The term "hydroxyl protecting group" refers to a protecting ester or ether group typically employed to block or protect the hydroxyl group while reactions involving other functional sites of the compound are performed. Hydroxyl protecting groups are disclosed in Greene, "Protective Groups In Organic Synthesis," (John Wiley & Sons, New York (1981)). Ther term "perfluoroalkyl" refers to an alkyl group wherein all of the hydrogens have been substituted with fluorides. The term "pharmaceutically acceptable prodrugs" refers to those prodrugs of the compounds of the present invention which are, within the scope of sound medical judgement, suitable for use in contact with the tissues of humans and lower mammals without undue -39- toxicity, irritation, and allergic response, are commensurate with a reasonable benefit/risk ratio, and are effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention. The term "prodrug" refers to compounds which are rapidly transformed in vivo to the parent compound of the above formula, for example, by hydrolysis in blood. A thorough discussion is provided in T. Higuchi and V. Stella, "Pro-drugs as Novel Delivery Systems, " Vol. 14 of the A.C.S. Symposium Series, and in Edward B. Roche, ed., "Bioreversible Carriers in Drug Design," American Pharmaceutical Association and Pergamon Press, 1987, both of which are hereby incoφorated by reference. The term "thioalkoxy" refers to an alkyl group attached to the parent molecular group through a sulfur atom. Compounds of the present invention may exist as stereoisomers where asymmetric or chiral centers are present. The present invention contemplates various stereoisomers and mixtures thereof. Stereoisomers include enantiomers and diastereomers. Individual stereoisomers of compounds of the present invention can be prepared synthetically from commercially available starting materials which contain asymmetric or chiral centers or by preparation of racemic mixtures followed by resolution well-known to those of ordinary skill in the art. These methods of resolution are exemplified by (1) attachment of a mixture of enantiomers to a chiral auxiliary, separation of the resulting mixture of diastereomers by recrystalhzation or chromatography and liberation of the optically pure product from the auxiliary or (2) direct separation of the mixture of optical enantiomers on chiral chromatographic columns. Geometric isomers may also exist in the compounds of the present invention. The present invention contemplates the various geometric isomers and mixtures thereof resulting from the arrangement of substituents around a carbon-carbon double bond or disposition of substituents around a ring. Substituents around a carbon-carbon double bond are designated as being in the Z or E configuration where the term "Z" refers to substituents on the same side of the carbon-carbon double bond and the term "E" refers to substituents on opposite sides of the carbon-carbon double bond. Compounds of the present invention can exist as rotamers. Rotamers are formed from hinderance around an amide bond to provide 2 or more distinct compounds which can be separated by means well-known to those skilled in the art. Determination of Biological Activity -40- Cell and Culture Conditions Human peripheral blood mononuclear cells were cultured in RPMI 1640 medium supplemented with 10 μg/ml gentamicin, 50 uM 2-mercaptoethanol, IX MEM non-essential amino acids (Sigma Chemical Co., St. Louis, MO), 100 U/ml sodium penicillin G, 100 μg/ml streptomycin sulfate, 2 mM L-glutamine, 1 mM sodium pyruvate (Life Technologies, Grand Island, NY) and 10% fetal bovine serum (Hyclone, Logan, UT) at 37 °C with 5% CO2- Preparation of Human Peripheral Blood Mononuclear Cells The procedure in Current Protocols in Immunology, Volume 1 , Published by the Greene Publishing Associates and John Wiley & Sons, Inc, Edited by Richard Coico, 1994, hereby incoφorated by reference, was followed. Briefly, 50 ml of blood from human volunteers was collected in heparinized syringes and mixed. Blood was diluted 1 : 1 in Dulbecco's phosphate buffered saline (D-PBS) (Life Technologies, Grand Island, NY) and mixed. PBS-blood mixture was overlaid into 50 ml centrifuge tubes containing 15 ml Histopaque 1077 (Sigma Chemical Co., St. Louis, MO) and centrifuged at 500 X G for 30 minutes at room temperature. Cells at the interface from each Histopaque tube were removed and mixed with 5 ml of D-PBS. Each cell suspension was diluted to 50 ml with D-PBS, mixed and centrifuged at 400 X G for 15 minutes at room temperature. After most of the supernatant was removed, cells were resuspended to 40 ml with D-PBS per tube (2 tubes per donor). Cells were centrifuged at 400 X G for 10 minutes at room temperature. Pellets were resuspended in 10 ml of supplemented RPMI 1640 and cell number determined with a Coulter counter. Cells were diluted to a concentration of 0.5 X 10^ cells per mL. Human Concanavalin-A Proliferation Assay (Con HU Assay) The procedure in Current Protocols in Immunology, Volume 1, Published by the Greene Publishing Associates and John Wiley & Sons, Inc, Edited by Richard Coico, 1994, hereby incoφorated by reference, was followed. Briefly, test compounds were added to appropriate wells on 96-well tissue culture plates (Corning Glass Works, Corning, NY) in 20 μl of supplemented RPMI 1640. Human peripheral blood mononuclear cells were added to each well in 100 μl volumes (final cell concentration equal to 50,000 cells per well). After 15 minutes, 100 μl of 5 μg/ml concanavalin-A (Sigma Chemical Co., St. Louis, MO) in supplemented RPMI 1640 was added to a final concentration of 2.5 μg/ml. Plates were incubated for 3 days at 37° C with 5% CO 2 . On day 3, plates were pulsed with 0.5 μCi/well tritiated thymidine (New England Nuclear, Boston, MA). After 6 hours, plates were harvested -41- on a Tomtec 96-well harvester (Orange, CT). Glass filter mats were counted on a Matrix 9600 direct beta counter (Packard , Meriden, CT). Table 1 Inhibitory Potency of Representative Compounds in the Human Concanavalin-A Proliferation Assay (Con HU) % Inhibition of Example Number proliferation (at Con HU IC 50 (nM) concentrations of 1,10, or 100 μm) 68(1) - 1 2 KD - 100(10) 328 3 82 (100) 28806 4 100(100) 33666 5 100(10) 98 6 97(10) 403 7 35(1) - 9 100(10) 114 10 100(10) 376 11 98(10) 427 12 99(100) 2843 13 97(100) 538 14 99(100) 274 15 100(100) 4186 16 18(1) - 17 100(100) 374 18 9(1) - 19 10(1) - 20 2(1) - 21 14(1) - 22 4(1) - 23 98(100) 24 301 -42- 25 100(10) 396 26 24(1) - 27 100(10) 299 28 12(1) - 29 100(10) 51 30 6(1) - 31 100(100) 4038 32 100(100) 8436 35 65(1) - 40 36(1) - 41 100(10) 343 42 9(1) - 43 98(10) 354 44 29(1) - 45 18(1) - 46 10(1) - 48 85(1) 468 49 9(1) - 50 2(1) - 51 100(10) 778 52 26(1) - 53 99(100) 202 54 12(1) - 55 13(1) - 56 32(1) - 57 5(1) - 58 97(10) 484 59 54(1) - 60 100(100) 296 65 98(100) 1823 66 97(100) 1044 67 100(100) 254 -43- 68 99(100) 2437 69 98(100) 506 70 100(100) 913 71 87(10) 544 73 93(10) 388 74 83(100) 22826 75 100(100) 368 76 100(100) 3173 77 93(10) 655 78 95(100) 607 79 9(1) - 80 43(1) - 81 30(1) - 82 100(100) 468 83 99(10) 71 84 76(1) 712 85 93(100) 275 86 33(1) - 87 (-)52(1) - 88 29(1) - 89 99 (100) 1232 90 98(100) 144 91 99(100) 138 92 92 (100) 673 93 100(100) 365 94 3(10) - 95 47(10) 7280 96 99(100) 338 97 20(10) - 98 94(100) 4923 100 75 (100) 2154 101 100(100) 2227 -44- 102 100(100) 503 103 14(1) - 104 99(100) 394 105 100(10) 387 106 100(10) 237 107 99(10) 304 108 18(1) - 109 45(1) - 110 99(10) 314 111 76(100) 41000 112 (-)2(1) - 114 98(100) 84 115 71 (100) 51313 116 100(10) 154 117 100(100) 158 119 100(10) 572 120 100(100) 488 121 53 (100) 10565 122 15(1) - 123 99 (100) 256 124 99(100) 285 125 6(1) - 126 79(10) 4906 127 100(100) 487 128 25(1) - 129 100(100) 380 130 100(100) 336 132 56(10) 6215 133 97(10) 315 134 100(100) 2770 135 100(100) 207 136 99(100) 222 -45- 137 98(100) 120 138 99(10) 364 139 5(10) - 140 100(100) 298 141 4(1) - 142 99(10) 489 143 100(100) 1675 144 100(100) 240 145 94(100) 1593 146 98(100) 269 147 99(100) 71 148 94 (100) 529 149 100(100) 336 150 100(100) 244 151 99 (100) 295 154 52(10) 3817 156 16(1) - 157 42(10) 6761 158 30(1) - 159 93(10) 2928 160 KD - 161 99(100) 231 162 100(10) 44 163 98(100) 235 164 99(10) 39 165 57(10) 6703 166 11(1) - 167 100(100) 279 168 20(1) - 169 2(1) - 170 25(1) - 171 12(1) - -46- 172 48(1) - 173 28(1) - 174 99(10) 730 175 100(100) 562 176 12(1) - 177 4(1) - 178 14(1) - 47(10) 179 8871 180 95(10) 2872 181 100(10) 2240 182 83(10) 4668 183 94(10) 542 184 90(10) 420 185 26(1) - 186 14(1) - 187 86(1) 362 188 87(10) 485 189 24(1) - 190 3(1) - 191 99(1) 116 192 10(1) - 193 8(1) - 194 23(1) - 195 22(1) - 196 11(1) - 197 KD - 198 4(1) - 199 30(1) - 200 26(1) - 201 100(10) 364 202 6(1) - 203 KD - -47- 204 12(1) - 205 100(10) 196 206 100(10) 61 207 100(10) 372 208 99(10) 149 209 99(10) 33 210 100(10) 239 211 98(10) 39 212 99(10) 70 213 100(10) 434 214 100(10) 68 215 100(10) 126 216 100(10) 267 217 100(10) 218 218 100(10) 136 219 100(10) 214 220 100(10) 4232 221 98(10) 411 222 100(10) 760 223 100(10) 93 224 2(1) - 225 98(10) 154 226 100(10) 43 227 100(10) 257 228 99(10) 147 229 99(10) 40 230 64(1) - 231 100(10) 25 232 99(10) 172 233 100(10) 340 234 99(10) 61 235 100(10) 107 -48- 236 100(10) 180 237 100(100) 368 238 3(1) - 239 55(10) - 240 84(10) 507 241 10(1) - 242 3(1) - 243 99(10) 390 244 94(10) 523 245 100(100) 279 246 47(1) - 247 97(10) 375 248 100(10) 143 249 100(10) 182 250 100(100) 173 251 50(1) - 252 36(1) - 253 94(10) 447 254 9(1) - 255 12(1) - 256 100(10) 250 257 100(10) 387 258 16(1) - 259 5(1) - 260 96(10) 369 261 37(1) - 262 100(10) 419 263 100(10) 2932 264 100(10) 42 265 90(10) 3808 -49- 266 100(100) 322 267 38(1) - 268 100(10) 347 269 99(10) 392 270 100(10) 228 271 14(1) - 272 10(1) - 273 12(1) - 274 100(10) 2181 275 8(1) - 276 16(1) - 277 99(100) 1063 278 4(1) - 279 6(1) - 280 16(10) - 281 94(100) 1063 282 100(100) 248 283 99(100) 1045 287 24(1) 288 16(1) 289 22(1) 290 373 291 411 292 258 293 409 294 299 295 232 296 44 297 251 298 332 -50- 269 299 300 79 301 232 302 358 487 303 304 266 305 170 306 265 307 79 308 309 309 32 310 335 311 323 312 298 66 313 314 246 320 315 316 41 317 186 318 258 319 219 320 43 321 185 322 327 323 238 324 89 325 172 326 166 327 82 328 75 -51- 303 329 330 169 331 220 332 44 333 410 334 297 335 103 336 1826 337 221 338 164 339 369 340 251 341 191 342 238 343 250 344 251 345 273 346 117 347 288 348 114 349 224 350 240 351 309 352 141 353 174 354 75 355 282 356 247 357 1855 358 203 -52- 261 359 329 360 CD3 and CD28 Activation of Peripheral Blood T Cells and Determination of Secreted IL-2 Levels (C28 HU Assay) Human peripheral blood mononuclear cells (PBMC) were isolated by Ficoll-Hypaque seperation. PBMCs were stimulated with a combination of immobilized anti-CD3 and soluble anti CD28 mAbs as described in Faltynek, et al. J. Enzyme Inhibition 1995, 9, 111-122, hereby incoφorated by reference. Following a 24 hour incubation, cell supernatants were harvested and IL-2 levels were determined. 100 μl of 5 μg/ml monoclonal murine anti-human IL-2 antibody (Biosource International) in D-PBS was added to 96 well Maxisorb plates (Nunc) and incubated at 4 °C overnight. Plates were washed 4 times with D-PBS containing 0.05% Tween 20 (wash buffer) and blocked with D-PBS containing 1% BSA and 10 mM NaN 3 (Diluent Blocking buffer) for 1-3 hours at room temperature or overnight at 4°C. Plates were washed and recombinant human IL-2 diluted (at 10,000, 5,000, 2,500, 1,250, 625, 312.5, 156.25, 78, 39, 20 pg/ml) in diluent/blocking buffer containing a matched percentage of complete RPMI 1640 medium as the unknown samples. Tissue culture supernatant at various dilutions were added in triplicate at 100 μl/well. Plates were incubated for 2 hours at room temperature and washed 4 times with wash buffer. 100 μl of rabbit anti-human IL-2 (10 μg/ml, Genzyme) was added and incubated for 1 hour at room temperature. The incubation was followed by 4 washes and subsequent addition of 100 μl of 1 :2000 dilution of alkaline phosphatase-conjugated goat anti-rabbit F(ab')2 (Biosource International). After 1 hour the plates were washed 4 times and 100 μl of pNPP (Southern Biotech or Sigma) at 1 mg/ml in buffer was added. Color development was allowed to proceed at room temperature for 20 minutes before addition of 50 μl of 2 N NaOH. Absorbance at 405 nm was determined using a plate reader (Molecular Devices). IL-2 concentrations were calcualted using SoftMax (Molecular Devices) based on the IL-2 standard solutions. Table 2 Inhibition of IL-2 Secretion by Representative Compounds in the C28 Assay -53- % Inhibition of IL-2 Example Number secretion C28 Assay (At concentrations of IC 50 (nM) 1,10, or 100 μM) 8 20(1) - 24 83(1) 380 6(1) - 33 34 13(100) - 10(1) 36 - 16(1) 38 - 14(1) - 39 47 2(1) - 61 32(1) - 62 96(100) 5035 63 19(1) - 64 86(100) 22274 72 11 (1) - 9(1) - 99 19(1) - 113 27(1) - 118 32(1) - 131 3(1) - 152 153 94(100) 457 155 8(1) - 250 97(100) 102 266 88(100) 314 284 17(1) - 26(1) - 285 2(1) 286 " Measurement of IL-5 and IL-4 Levels in Human T Cells (IL-4 and IL-5 Assays) Human T cells (HUT 78) were cultured to lxl0 6 /mL in RPMI 1640 medium containing 10% fetal calf -54- serum, 100 U/mL penicillin and 100 μg/mL streptomycin. Cultures were then centrifuged, to pellet the cells, and cells resuspended in fresh medium to the same density. 0.2 mL samples of cells were incubated in 96-well plates with 8 μL of various concentrations of compound freshly diluted with the above medium from 100 mM solvent stocks (ethanol or DMSO). Immediately after addition of compound, cells were stimulated by addition of 2 ng/mL phorbol 12-myristate 13-acetate (1 μL of freshly prepared solution of stock (in DMSO) diluted with the above medium added to cells) and 750 μg/mL anti-CD3 (pre-coated at 4 °C overnight). Cell cultures were incubated at 37 °C for 32 hours, then cells pelleted by centrifugation and the supernatants harvested for ELISA. IL-4 and IL-5 ELISA's were performed according to standard procedures. Inhibition was calculated relative to cytokine levels produced from control stimulated cells not treated with compound. Table 3 Inhibition of IL-4 and IL-5 Secretion in Human T Cells by Representative Compounds and Comparison with FK-506 IL-4 Inhibition IL-5 Inhibition Example Number IC50 (nM) IC50 (nM) FK-506 0.7 0.5 24 150 150 250 50 80 266 110 150 209 5 38 6 8 50 264 4.8 22 As shown in Tables 1, 2 and 3, the compounds are useful for inhibiting cytokine (IL-2, IL-4 and IL-5) production and cellular proliferation in stimulated human T cell lines or human peripheral blood mononuclear cells and therefore have utility in the treatment of diseases that are prevented by or ameliorated with cytokine inhibitors. The compounds of the invention, including but not limited to those specified in the examples, possess immunomodulatory activity in mammals, especially humans. As immunosuppressants, the compounds of the present invention are useful for the treatment and -55- prevention of immune-mediated diseases such as the resistance to transplantation of organs or tissue such as heart, kidney, liver, medulla ossium, skin, cornea, lung, pancreas, intestinum tenue, limb, muscle, nerves, duodenum, small-bowel, pancreatic-islet-cell, and the like; graft- versus-host diseases brought about by medulla ossium transplantation; autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, Hashimoto's thyroiditis, multiple sclerosis, myasthenia gravis, type I diabetes, uveitis, allergic encephalomyelitis, glomerulonephritis, and the like. Further uses include the treatment and prophylaxis of inflammatory and hypeφroliferative skin diseases and cutaneous manifestations of immunologically-mediated illnesses, such as psoriasis, atopic dermatitis, contact dermatitis and further eczematous dermatitises, seborrhoeis dermatitis, lichen planus, pemphigus, bullous pemphigoid, epidermolysis bullosa, urticaria, angioedemas, vasculitides, erythemas, cutaneous eosinophilias, lupus erythematosus, acne and alopecia areata; various eye diseases (autoimmune and otherwise) such as keratoconjunctivitis, vernal conjunctivitis, uveitis associated with Behcet's disease, keratitis, heφetic keratitis, conical cornea, dystrophia epithelialis corneae, corneal leukoma, and ocular pemphigus. In addition reversible obstructive airway disease, which includes conditions such as asthma (for example, bronchial asthma, allergic asthma, intrinsic asthma, extrinsic asthma and dust asthma), particularly chronic or inveterate asthma (for example, late asthma and airway hyper-responsiveness), bronchitis, allergic rhinitis, and the like are targeted by compounds of this invention. Inflammation of mucosa and blood vessels such as gastric ulcers, vascular damage caused by ischemic diseases and thrombosis. Moreover, hypeφroliferative vascular diseases such as intimal smooth muscle cell hypeφlasia, restenosis and vascular occlusion, particularly following biologically- or mechanically- mediated vascular injury, could be treated or prevented by the compounds of the invention. Other treatable conditions include but are not limited to ischemic bowel diseases, inflammatory bowel diseases, necrotizing enterocolitis, intestinal inflammations/allergies such as Coeliac diseases, proctitis, eosinophilic gastroenteritis, mastocytosis, Crohn's disease and ulcerative colitis; nervous diseases such as multiple myositis, Guillain-Barre syndrome, Meniere's disease, polyneuritis, multiple neuritis, mononeuritis and radiculopathy; endocrine diseases such as hyperthyroidism and Basedow's disease; hematic diseases such as pure red cell aplasia, aplastic anemia, hypoplastic anemia, idiopathic thrombocytopenic puφura, autoimmune hemolytic anemia, agranulocytosis, pernicious anemia, megaloblastic anemia and anerythroplasia; bone diseases such as osteoporosis; respiratory diseases such as sarcoidosis, fibroid lung and idiopathic interstitial pneumonia; skin disease such as dermatomyositis, leukoderma vulgaris, ichthyosis vulgaris, -56- photoallergic sensitivity and cutaneous T cell lymphoma; circulatory diseases such as arteriosclerosis, atherosclerosis, aortitis syndrome, polyarteritis nodosa and myocardosis; collagen diseases such as scleroderma, Wegener's granuloma and Sjogren's syndrome; adiposis; eosinophilic fasciitis; periodontal disease such as lesions of gingiva, periodontium, alveolar bone and substantia ossea dentis; nephrotic syndrome such as glomerulonephritis; male pattern aleopecia or alopecia senilis by preventing epilation or providing hair germination and/or promoting hair generation and hair growth; muscular dystrophy; Pyoderma and Sezary's syndrome; Addison's disease; active oxygen-mediated diseases, as for example organ injury such as ischemia-reperfusion injury of organs (such as heart, liver, kidney and digestive tract) which occurs upon preservation, transplantation or ischemic disease (for example, thrombosis and cardiac infarction); intestinal diseases such as endotoxin-shock, pseudomembranous colitis and colitis caused by drug or radiation; renal diseases such as ischemic acute renal insufficiency and chronic renal insufficiency; pulmonary diseases such as toxinosis caused by lung-oxygen or drug (for example, paracort and bleomycins), lung cancer and pulmonary emphysema; ocular diseases such as cataracta, siderosis, retinitis, pigmentosa, senile macular degeneration, vitreal scarring and corneal alkali burn; dermatitis such as erythema multiforme and others such as sinusitis, gingivitis, periodontitis, sepsis, pancreatitis, diseases caused by environmental pollution (for example, air pollution), aging, carcinogenesis, metastasis of carcinoma and hypobaropathy; diseases caused by histamine or leukotriene-C4 release; Behcet's disease such as intestinal-, vasculo- or neuro-Behcet's disease, and also Behcet's which affects the oral cavity, skin, eye, vulva, articulation, epididymis, lung, kidney and so on. Furthermore, the compounds of the invention are useful for the treatment and prevention of hepatic disease such as immunogenic diseases (for example, chronic autoimmune liver diseases such as autoimmune hepatitis, primary biliary cirrhosis and sclerosing cholangitis), partial liver resection, acute liver necrosis (e.g. necrosis caused by toxin, viral hepatitis, shock or anoxia), B-virus hepatitis, non-A/non-B hepatitis, cirrhosis (such as alcoholic cirrhosis) and hepatic failure such as fulminant hepatic failure, late-onset hepatic failure and "acute-on-chronic" liver failure (acute liver failure on chronic liver diseases), and moreover are useful for various diseases because of their useful activity such as augmention of chemotherapeutic effect, cytomegalovirus infection, particularly HCMV infection, anti-inflammatory activity, sclerosing and fibrotic diseases such as nephrosis, scleroderma, pulmonary fibrosis, arteriosclerosis, congestive heart failure, ventricular hypertrophy, post-surgical adhesions and scarring, stroke, myocardial infarction and injury associated with ischemia and reperfusion, and the like. -57- The present invention also provides pharmaceutical compositions that comprise compounds of the present invention formulated together with one or more non-toxic pharmaceutically acceptable carriers. The pharmaceutical compositions can be specially formulated for oral administration in solid or liquid form, for parenteral injection or for rectal administration. The pharmaceutical compositions of this invention can be administered to humans and other animals orally, rectally, parenterally , intracisternally, intravaginally, intraperitoneally or topically (such as powders, ointments or drops), bucally or as an oral or nasal spray. The term "parenteral" administration refers to modes of administration that include intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous and intraarticular injection and infusion. Pharmaceutical compositions of this invention for parenteral injection comprise pharmaceutically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants. These compositions may also contain adjuvants such as preservative, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride, and the like. Prolonged absoφtion of the injectable pharmaceutical form can be brought about by the inclusion of agents (such as aluminum monostearate and gelatin) that delay absoφtion . In some cases, in order to prolong the effect of the drug, it is desirable to slow the absoφtion of the drug from subcutaneous or intramuscular injection. This can be accomplished by the use of a liquid suspension of crystalline or amoφhous material with poor water solubility. The rate of absoφtion of the drug then depends upon its rate of dissolution that, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed -58- absoφtion of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly (anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacterial- retaining filter or by incoφorating sterilizing agents in the form of sterile solid compositions that can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use. Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol and silicic acid; b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and acacia; c) humectants such as glycerol; d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate; e) solution retarding agents such as paraffin; f) absoφtion accelerators such as quaternary ammonium compounds; g) wetting agents such as cetyl alcohol and glycerol monostearate; h) absorbents such as kaolin and bentonite clay and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols, and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and may also be of a composition such that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally or in delayed fashion. Examples of embedding compositions that can be used include polymeric substances and waxes. -59- The active compounds may also be in micro-encapsulated form, if appropriate, with one or more of the above-mentioned excipients. The compounds of the present invention may be used in the form of pharmaceutically acceptable salts derived from inorganic or organic acids. By "pharmaceutically acceptable salt" is meant those salts which are, within the scope of sound medical judgement, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well-known in the art. For example, S. M. Berge, et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66: 1 et seq. The salts may be prepared in situ during the final isolation and purification of the compounds of the invention or separately by reacting a free base function with a suitable acid. Representative acid addition salts include, but are not limited to acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethansulfonate, lactate, maleate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, palmoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, phosphate, glutamate, bicarbonate, p-toluenesulfonate and undecanoate. Also, the basic nitrogen-containing groups can be quaternized with such agents as lower alkyl halides such as methyl, ethyl, propyl, and butyl chlorides, bromides and iodides; dialkyl sulfates like dimethyl, diethyl, dibutyl and diamyl sulfates; long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides; arylalkyl halides like benzyl and phenethyl bromides and others. Water or oil-soluble or dispersible products are thereby obtained. Examples of acids which may be employed to form pharmaceutically acceptable acid addition salts include such inorganic acids as hydrochloric acid, hydrobromic acid, sulphuric acid and phosphoric acid and such organic acids as oxalic acid, maleic acid, succinic acid and citric acid. Basic addition salts can be prepared in situ during the final isolation and purification of compounds of this invention by reacting a carboxylic acid-containing moiety with a suitable base such as the hydroxide, carbonate or bicarbonate of a pharmaceutically acceptable metal cation or with ammonia or an organic primary, secondary or tertiary amine. Pharmaceutically acceptable salts include, but are not limited to, cations based on alkali metals or alkaline earth metals such as lithium, sodium, potassium, calcium, magnesium and aluminum salts and the like and nontoxic quaternary ammonia and amine cations including -60- ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine and the like. Other representative organic amines useful for the formation of base addition salts include ethylenediamine, ethanolamine, diethanolamine, piperidine, piperazine and the like. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethyl formamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan and mixtures thereof. Besides inert diluents, the oral compositions may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring and perfuming agents. Suspensions, in addition to the active compounds, may contain suspending agents such as ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, and tragacanth and mixtures thereof. Compositions for rectal or vaginal administration are preferably suppositories that can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax that are solid at room temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. Compounds of the present invention can also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-lamellar hydrated liquid crystals that are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizable lipid capable of forming liposomes can be used. The present compositions in liposome form can contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients, and the like. The preferred lipids are the phospholipids and the phosphatidyl cholines (lecithins), both natural and synthetic. -61- Methods to form liposomes are known in the art. See, for example, Prescott, Ed., "Methods in Cell Biology," Volume XIV, Academic Press, New York, N.Y. (1976), p. 33 et seq. Compounds of the present invention may also be coadministered with one or more immunosuppressant agents. The immunosuppressant agents within the scope of this invention include, but are not limited to, IMURAN® (azathioprine sodium), brequinar sodium, SPANIDIN® (gusperimus trihydrochloride, also known as deoxyspergualin), mizoribine (also known as bredinin), CELLCEPT® (mycophenolate mofetil), Cyclosporin A in its various formulations (NEORAL®, SANDIMMUNE®, and generic formulations), PROGRAF® (tacrolimus, also known as FK-506), RAPAMUNE® (sirolimus also known as rapamycin), and leflunomide (also known as HWA-486), glucocorticoids, such as prednisolone and its derivatives, antibody therapies such as orthoclone (OKT3) and Zenapax®, and antithymyocyte globulins, such as thymoglobulins. Dosage forms for topical administration of a compound of this invention include powders, sprays, ointments and inhalants. The active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives, buffers or propellants that can be required. Opthalmic formulations, eye ointments, powders and solutions are also contemplated as being within the scope of this invention. Actual dosage levels of active ingredients in the pharmaceutical compositions of this invention can be varied so as to obtain an amount of the active compound(s) that is effective to achieve the desired therapeutic response for a particular patient, compositions, and mode of administration. The selected dosage level will depend upon the activity of the particular compound, the route of administration, the severity of the condition being treated and the condition and prior medical history of the patient being treated. However, it is within the skill of the art to start doses of the compound at levels lower than required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. Generally dosage levels of about 1 to about 50, more preferably of about 5 to about 20 mg, of active compound per kilogram of body weight per day when administered orally to a mammalian patient. If desired, the effective daily dose can be divided into multiple doses for puφoses of administration, e.g. two to four separate doses per day. Preparation of Compounds of this Invention -62- The compounds of this invention can be prepared by a variety of synthetic routes. Representative procedures are shown in Schemes 1-12 wherein Rj, R 2 , R 3 , R4, R5. L 3 , Q, B and E are defined above unless otherwise indicated. Abbreviations Abbreviations that have been used in the descriptions of the schemes and the examples that follow are: THF for tetrahydrofuran; DMF for N,N-dimethylformamide; DMSO for dimethylsulfoxide; Boc for tert-butylcarbonyloxy; DCC for dicyclohexylcarbodiimide; EDC for l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; HBTU for O- benzotriazol-yl-N,N,N'N'-tetramethyluronium hexafluorophosphate; and DMAP for 4- dimethylaminopyridine. Starting materials, reagents and solvents were purchased from Aldrich Chemical Company (Milwaukee, WI), Maybridge Chemical Company (Tintagel, Cornwall, U.K.), Lancaster (Windham, NH), Sigma (St. Louis, MO), ACROS, and Chess (Mannheim, Germany). Description of Intermediates in the Schemes Compounds of Formula I are designated by the small-case numbers (i), (ii). (iii), (iv), etc. The small-case letters ("-a," "-b," and "-c") that follow the small-case numbers indicate the disposition of the substituent E on ring Q relative to the position of the pyrazole or triazole ring as defined in the schemes 1-12. Intermediates in the syntheses of compounds of Formula I are further designated by a capital letter (A, B, C, etc). -63- Scheme 1 R 3 H 2 R2 ^( N— Q~N0 2 L ,N-Q-NOι H Ri ^^N Example a (4-nitrophenylhydrazine) Example (i)-a A (Q is 1 ,4-disubstituted phenyl) Example b (3-nitrophenylhydrazine) Example (i)-b A (Q is 1,3-disubstituted phenyl) Example c (2-nitrophenylhydrazine) Example (i)-c A (Q is 1,2-disubstituted phenyl) Example (xviii)-a A (Q is 1.4-disubstituted pheny R 3 Example (xix)-a A (Q is 1 ,4-disubstituted phenyl) R ^ L .N-Q- NH 2 Example (xx)-a A (Q is 1 ,4-disubstituted phenyl) R, -^ N Example (xxi)-a A (Q is 1 ,4-disubstituted phenyl) Example (i)-a B (Q is 1 ,4-disubstituted phenyl) Example (i)-b B (Q is 1,3-disubstituted phenyl) Example (i)-c B (Q is 1,2-disubstituted phenyl) Example (xviii)-a B (Q is 1 ,4-disubstituted phenyl) Example (xix)-a B (Q is 1, 4-disubstituted phenyl) Example (xx)-a B (Q is 1, 4-disubstituted phenyl) Example (xxi)-a B (Q is 1 ,4-disubstituted phenyl) As shown in Scheme 1, the two-step construction of the 1,4- ("-a"), 1,3- ("-b"), and 1,2-disubstituted ("-c") anilines that served as precursors to compounds of Formula I began with condensation of 1,4-, 1,3- or 1,2-nitrophenylhydrazine ("a," "b," and "c" respectively) with appropriately substituted 2,4-pentanediones in the presence of an acid catalyst such as p- toluenesulfonic acid, HCl, or H 2 SO4 to provide nitro intermediates (i)-a A, (i)-b A, (i)-c A, (xviii)-a A, (xix)-a A, (xx)-a A, and (xxi)-a A. Conversion of the nitro intermediates to the corresponding aniline precursors (i)-a B, (i)-b B, (i)-c B, (xviii)-a B, (xix)-a B, (xx)-a B, and (xxi)-a B was accomplished with hydrogen gas in the presence of a catalyst, preferably -64- palladium on carbon. An alternative method was reduction with tin(II) chloride in the presence of acid, preferably hydrochloric acid, at elevated temperature. A more preferred method of reduction was with iron powder with ammonium chloride in ethanol/water. -65- Scheme 2 Example a Example (xxiii)-a A R 2 OH R 2 OH Ri ■ *- R N- ^ XT N0 2 N α NH 2 Example (xxiii)-a B Example (xxiii)-a C As shown in Scheme 2, replacement of the pentanedione in Scheme 1 with the appropriately substituted acetoacetate followed by ring closure with a non-nucleophilic base such as K 2 CO 3 provided nitro intermediate (xxxiii)-a B which was converted to aniline precursor (xxxiii)-a C with reducing agents such as those described in Scheme 1. -66- Scheme 3 R 2 R 3 R y NO- R 2 Example (xxii)-a A -rt O NH 2 Example (xxii)-a B As shown in Scheme 3, an alternative route to aniline precursors was direct displacement of a leaving group, preferably fluoride, from 4-fluoronitrobenzene by the sodium salt of a preformed, substituted pyrazole ring followed by conversion of the nitro intermediate (xxii)-a A to aniline precursor (xxii)-a B with reducing agents such as those described in Scheme 1. -67- Scheme 4 R 3 2 ^ _ R N N > "NH2 R yyr R 5 L3 - B Formula I -L 3 - is -NHC(O)- Example i)-a B (Q is 1 ,4-disubstituted phenyl) Example (i)-a Example i)-b B (Q is 1,3-disubstituted phenyl) Example (i)-b Example i)-c B (Q is 1 ,2-disubstituted phenyl) Example (i)-c Example xviii)-a B (Q is 1 ,4-disubstituted phenyl) Example (xviii)-a Example xix)-a B (Q is 1 ,4-disubstituted phenyl) Example (xix)-a Example xx)-a B (Q is 1 ,4-disubstituted phenyl) Example (xx)-a Example xxi)-a B (Q is 1 ,4-disubstituted phenyl) Example (xxi)-a Example xxii)-a B (Q is 1 ,4-disubstituted phenyl) Example (xxii)-a Example (xxiii)-a C (Q is 1, 4-disubstituted phenyl) Example (xxiii)-a As shown in Scheme 4, conversion of the aniline precursors to compounds of Formula I was achieved by treatment of the anilines exemplified by examples (i)-a B, (i)-b B, (i)-c B, (xviii)-a B, (xix)-a B, (xx)-a B, (xxi)-a B, (xxii)-a B, and (xxiii)-a C with acid chlorides in the presence of base such as triethylamine, diisopropylethylamine or pyridine in dichloromethane. The same aniline intermediates may be reacted with carboxylic acids in dichloromethane in the presence of coupling agents such as DCC, HBTU or EDC with DMAP, preferably EDC with DMAP. -68- Scheme 5 R 3 R4 (ι)-a B «- I >N -Q-L 3 -B R ^N I R 5 Formula I Example (ii)-a -L 3 - is -NHC(O)NH- Example (iii)-a -L 3 - is -NHSO 2 - Example (vi)-a -L 3 - is -NH(CH 2 ) m - As shown in Scheme 5, conversion of Example (i)-a B to compounds of Formula I, as exemplified by examples (ii)-a, (iii)-a, and (vi)-a, was achieved by treatment of Example (i)-a B with isocyanates, sulfonyl chlorides, or aldehydes in the presence of appropriate reducing agents, respectively. -69- Scheme 6 R 3 ?4 R ^ 2 1 .NH + Z-^ ^>— N0 2 ^μ R 3 «L4 Ri ' N Ri N Y R 5 R 5 R 4 is hydrogen; R 5 is alkoxycarbonyl((x)-a B); haloalkyl ((xi)-a A and (xii)-a A); halo ((xiii)-a A and (xvi)-a A); alkyl ((xiv)-a A); alkoxy ((xv)-a A); or substituted heterocycle ((xvii)-a A) ^μ R 3 - RL4 R 2 ^ I T N 3 -Q y-L 3 -B R l N I R 5 5 R 5 is alkoxycarbonyl((x)-a C); Formula I haloalkyl ((xi)-a B and (xii)-a B); L 3 is -NR 6 C(W)-; halo ((xiii)-a B and (xvi)-a B); R 6 is H; and W is O alkyl ((xiv)-a B); R 5 is alkoxycarbonyl((x)-a); alkoxy ((xv)-a B); or haloalkyl ((xi)-a and (xii)-a ); substituted heterocycle ((xvii)-a B) halo ((xiii)-a and (xvi)-a ); alkyl ((xiv)-a ); alkoxy ((xv)-a ); or substituted heterocycle ((xvii)-a ) As shown in Scheme 6, the displacement and reduction chemistry described in Scheme 3 for the synthesis of the aniline precursors (where R 4 and R5 are hydrogen) was also employed for the synthesis of aniline precursors where at least one of R4 and R5 is other than hydrogen. Anilines (x)-a C, (xi)-a B, (xii)-a B, (xiii)-a B, (xiv)-a B, (xv)-a B, (xvi)-a B, and (xvii)-a B were then converted to compounds of Formula I (exemplified by (x)-a, (xi)-a, -70- (xii)-a, (xiii)-a, (xiv)-a, (xv)-a, (xvi)-a, and (xvii)-a by the coupling conditions described in Scheme 4. -71- Scheme 7 (i)-a ► I N-Q -L 3 -B R^ N I R 5 Formula I Example (iv)-a L 3 is -NR 6 C(W)-; R 6 is CH 3 ; and W is O Compounds with modified, preformed linker groups are exemplified in Scheme 7. Compounds of Formula I (exemplified by Example (i)-a ) were alkylated at the amide bond nitrogen with methyl iodide in the presence of base, preferably potassium hydroxide to provide compounds of Formula I exemplified by Example (iv)-a. -72- Scheme 8 H 2 NHr .^\ C0 2 Et R l (v)-a A *2^ R 3 _ ■ C0 2 H Ri N R / _^ C(0)C1 (v)-a B (v)-a C R 3 N -^T ~L3_]B Formula I -L 3 - is -C(O)NH- (v)-a As shown in Scheme 8, compounds of Formula I derived from intermediates other than anilines were prepared from intermediate ester Example (v)-a A. Construction of the pyrazole ring from ethyl 4-hydrazinobenzoate according to Example (i)-a (Method 1) provided Example (v)-a A which was then hydrolyzed to carboxylic acid (v)-a B with base, preferably sodium hydroxide. Example (v)-a B was then elaborated to compounds of Formula I by conversion to the acid chloride (v)-a C with reagents such as thionyl chloride followed by treatment with amines in the presence of a base such as pyridine or triethylamine. -73- Scheme 9 R 3 R 3 (v)-a A > ■ JL N-Q-CHO >~ I N -Q-L 3 -B Ri N R^N I R 5 (vii)-a A Formula I (vii)-a L 3 is -(CH 2 ) m NR 8 -; R 8 is hydrogen; and m is 1 and (viii)-a L 3 is -C(H)=N- As shown in Scheme 9, Example (v)-a A was converted to aldehyde (vii)-a A by treatment with a reducing agent, preferably DIBAl-H at reduced temperature. Example (vii)-a A was then elaborated to compounds of Formula I by reductive amination or condensation (Example (vii)-a and Example (viii)-a, respectively by Method 13). -74- Scheme 10 (vii)-a A + B-P(Ph) 3 + Br " ► J^ ^_ Lr B (ix)-a A R i N 5 Formula I (ix)-a L 3 is Z and E alkenylene As shown in Scheme 10, treatment of Example (vii)-a A with ylides such as Example (ix)-a A also provided compounds of Formula I (exemplified by (ix)-a). -75- Scheme 11 R 2 R 2 R 3 , 3 C ^ N. R r N-.INTNa + + n RI ^ , N ^ N' N0 2 N0 2 (xxiv)-a A R 2 R3 R 3 RΛ K2 ^^N I R ι ~ ~ - ^ ^ L NN--QQ--IL 3 -B τ R> ^-K N i I NH 2 R 5 (xxiv) '-a B c Formul ιa 1 T L 3 is -NHC(O)- (xxiv)-a As shown in Scheme 11, the displacement and reduction chemistry described in Scheme 3 for the synthesis of the aniline precursors was also employed for the synthesis of precursors of compounds of Formula I where Q is a heterocycle, such as pyridine. 2-Chloro- 5-nitroρyridine was converted to nitro precursor (xxiv)-a A by treatment with the sodium salt of a preformed, substituted pyrazole ring. Example (xxiv)-a A was converted to aniline intermediate (xxiv)-a B by the reduction chemistry described in Scheme 1 then to compounds of Formula I by the coupling chemistry described in Scheme 4. -76- Scheme 12 o R 3 1 ^ Example a + H 3 ι CH 3 H Ri (xxv)-a A R 3 R 3 I i N- NH 2 I N«s, N \ R ι R l (xxv)-a B Formula I L 3 is -NHC(O)- (xxv)-a As shown in Scheme 12, construction of the substituted triazole rings of the compounds of Formula I was achieved by treatment of Example a (4-nitrophenylhydrazine) with diacetamide in the presence of acid, preferably sulfuric acid, to provide nitro intermediate (xxv)-a A. Example (xxv)-a A was converted to aniline intermediate (xxv)-a B with reducing agents such as those described in Scheme 1. Example (xxv)-a B was then converted to compounds of Formula I by the coupling chemistry described in scheme 4. Example (i -a. (i)-b. and (iVc Compounds of Formula I where R^ and R are CFr. Ri is H: Z is carbon; Q is 1.4-. 1.3-. and 1.2-disubstituted phenyl: R4_and Rs are hydrogen: L^ is -N(R^)C(W)- where W is O and Rf, is H Example (i)-a A. (i)-b A. and (i)-c A (Method 1) A solution of a, b, or c (1 equivalent), l,l,l,5,5,5-hexafluoro-2,4-pentanedione (1.2 equivalents), and p-toluenesulfonic acid (1 mmol) in toluene was refluxed for 18 hours in a Dean-Stark apparatus, diluted with ethyl acetate, washed sequentially with 1M HCl and saturated aqueous NaHCO 3 , dried (MgSO4), and concentrated. The residue was purified by -77- flash chromatography on silica gel with ethyl acetate/hexane to provide the desired compounds. Example (iVa A. (iVb A. and (iVc A (Method 2) A solution of a, b, or c (1 equivalent) and l,l,l,5,5,5-hexafluoro-2,4-pentanedione (1.2 equivalents) in 4M hydrochloric acid (10-12 equivalents) and ethanol was refluxed overnight and concentrated. The residue was dissolved into ethyl acetate, washed sequentially with IM HCl and brine, dried (Na 2 SO4), and concentrated to provide the desired compounds. (Example (i)-a A) J H NMR (DMSO-d 6 , 300 MHz) δ 8.55-8.38 (dt, 2H), 7.78-7.74 (dt, 2H), 7.17 (s, lH); MS (DCI/NH 3 ) m/e 313 (reduced to aniline in MS, M+NH 4 ) + . (Example (i)-b A) Η NMR (DMSO-d 6 , 300 MHz) δ 8.6 (t, 1H), 8.5 (m, 1H), 8.2 (dd, 1H), 8.0 (t, lH), 7.9 (s, 1H); (Example (i)-c A) *H NMR (DMSO-d 6 , 300 MHz) δ 8.38 (dd, 1H), 8.08-7.99 (m, 4H). Example (iVa B. (iVb B. and (iVc B (Method 3) A solution of (i)-(a, b, or c) A in ethyl acetate was treated with SnCl 2 (4 equivalents) at reflux (in some cases, the addition of concentrated hydrochloric acid (catalytic to 1 equivalent) led to a cleaner reduction), cooled, washed with saturated NaHCO 3 , dried (Na 2 SO 4 ), and concentrated. The residue was purified by column chromatography on silica gel with ethyl acetate/hexane or acetone/hexane to provide the desired compounds. Example (iVa B. (iVb B. and (iVc B (Method 4) A solution of (i)-(a, b, or c) A and 5-10% palladium on carbon in ethyl acetate was hydrogenated at 1 -4 atm, filtered through a short silica gel plug, and concentrated to provide the desired compounds. (Example (i)-a B) *H NMR (DMSO-d 6 , 300 MHz) δ 7.69 (s, 1H), 7.16 (d, 2H), 6.64 (d, 2H), 5.68 (s, 2H). (Example (i)-b B) l U NMR (DMSO-d 6 , 300 MHz) δ 7.8 (s, 1H), 7.2 (t, 1H), 6.8 (d, 1H), 6.7 (s, 1H), 6.6 (d, 1H), 5.6 (s, 2H); (Example (i)-c B) ] H NMR (DMSO-d 6 , 300 MHz) δ 7.73 (s, 1H), 7.25 (t, 1H), 7.11 (d, 1H), 6.84 (d, 1H), 6.6 (t, 1H), 5.27 (s, 2H). Example (D-a -78- Compounds of Formula I (Method 5) A solution of (i)-a B (1 equivalent), B-C(O)Cl (2 equivalents), and polyvinylpyridine in dichloromethane in a capped test tube was shaken overnight, treated with a primary benzyl amine resin, preferably Aminomethyl ResinΗCl (Midwest Bio-Tech, Fishers, IN) shaken for an additional 2 hours, eluted through a silica gel plug with acetone, and concentrated. The residue was purified by flash chromatography on silica gel to provide the desired compounds. Example (i)-a Compounds of Formula I (Method 6) A solution of (i)-a B (1 equivalent), B-C(O)Cl (1-1.5 equivalents), and base (preferably pyridine or triethylamine, 1-10 equivalents) in an appropriate solvent, preferably dichloromethane or THF, was shaken overnight in a capped test tube, diluted with ethyl acetate, washed with saturated NaHCO 3 and IM HCl, and concentrated. The residue was purified by flash chromatography on silica gel to provide the desired compounds. Example (i)-a Compounds of Formula I (Method 7) Example (i)-a B (1 equivalent), the appropriate carboxylic acid (B-CO 2 H, 1-2 equivalents), and EDC (1-1.5 equivalents), and DMAP (catalytic to 1 equivalent) in dichloromethane was shaken in a capped test tube for 18 hours at a temperatures between 25 and 60 °C, extracted with IN hydrochloric acid and water, dried (Na 2 SO4), and concentrated. The residue was purified by flash chromatography on silica gel to provide the desired compounds. Example (i)-b Compounds of Formula I where Rj ^ and R^ are CF^: R? is H: Z is carbon: Q is 1.3-disubstituted phenyl: R4_and Rs are hydrogen: LΈ is -N(R )C(WV: W is O and R is H Example (i)-b B was processed as in Example (i)-a B (Method 5, 6, or 7) to provide the desired compounds. Example (i)-c Compounds of Formula I where -79- R^ and Rg are CF R 7 is H: Z is carbon: Q is 1.2-disubstituted phenyl: R _and Rs are hydrogen: L is -N(R^)C(WV where W is O and R is H Example (i)-c B was processed as in Example (i)-a B (Method 5, 6, or 7) to provide the desired compounds. Example (ii)-a (Method 8) Compounds of Formula I where R^ and R are CF2: R? is H: Z is carbon: O is 1.4-disubstituted phenyl: R4_and Rs are hydrogen: L? is -N(R^)C(O N(R 7 )- where Re and R 7 are H A mixture of (i)-a B (1 equivalent) and an isocyanate (B-N=C=O, 1 equivalent) in toluene was stirred at room temperature for 18 hours. The precipitate was collected by filtration, rinsed with a nonpolar solvent, preferably toluene or hexane, and dried to provide the desired compounds. Example (iii)-a (Method 9) Compounds of Formula I where R\ and R^ are CF2: R is H: Z is carbon; Q is 1.4-disubstituted phenyl: R4_and Rs are hydrogen: L2 is -NRήS(O) I ,-. p is 2 and Rή is H A mixture of (i)-a B (1 equivalent), a sulfonyl chloride (B-SO 2 Cl, 1-1.2 equivalents) and pyridine (3-4 equivalents) in dichloromethane at room temperature was shaken or stirred for 18 hours and purified by extractive workup or flash column chromatography on silica gel to provide the desired compounds. Example (iv)-a (Method 10) Compounds of Formula I where R^ and R^ are CF2: R? is H: Z is carbon: Q is 1.4-disubstituted phenyl: R4_and Rs are hydrogen: L^ is -N(R^)C(W)-: W is O: and R* is methyl A solution of Example (i)-a (1 equivalent) and iodomethane (4 equivalents) in THF was treated with KOH powder (5 equivalents), heated to reflux for 6 hours, cooled to room temperature (or stirred at room temperature for 20 hours), filtered and concentrated. The residue was purified by flash chromatography on silica gel to provide the desired compounds. Example (v)-a Compounds of Formula I where -80- R^ and R2 are CF2: R2 is H: Z is carbon: O is 1.4-disubstituted phenyl; R4_and Rs are hydrogen: L 2 is -C(W)N(RAV: W is O: and R is H Example (v)-a A A solution of ethyl 4-hydrazinobenzoate (1 equivalent) and l,l,l,5,5,5-hexafluoro-2,4- pentanedione (1.1 equivalents) in 4M HCl/ethanol were heated to reflux for 18 hours and concentrated. The residue was dissolved in dichloromethane and eluted through a silica gel plug with dichloromethane to provide the desired compound. ! H NMR (300 MHz, DMSO-d 6 ) δ 8.17 (d, 2H), 7.91 (s, IH), 7.8 (d, 2H), 4.38 (q, 2H), 1.35 (t, 3H). Example (v)-a B A solution of Example (v)-a A (1 equivalent) and NaOH (5 equivalents) in ethanol was heated to reflux for 2 hours, concentrated, redissolved in water, acidified with IN HCl to pH~4, and extracted with diethyl ether. The extract was washed with brine, dried (Na 2 SO4), and concentrated to provide the desired compound. J H NMR (DMSO-d 6 , 300 MHz) δ 13.4 (bs, IH), 8.15 (d, 2H), 7.88 (s, IH), 7.77 (d, 2H). Example (v)-a C Compounds of Formula I A solution of Example (v)-a B (1 equivalent) in thionyl chloride (22 equivalents) was heated to reflux for 3 hours and concentrated. Example (vVa (Method 11) Compounds of Formula I Example (v)-a C in dichloromethane was treated with amine (H 2 N-B, 1 equivalent) in the presence of pyridine (4 equivalents), and purified by flash chromatography on silica gel to provide the desired compounds. Example (viVa (Method 121 Compounds of Formula I where R^ and R2 are CF2: R2 is H: Z is carbon: O is 1.4-disubstituted phenyl: R4_and Rs are hydrogen: L2 is -NR^(alkylene) m -. RA is hydrogen, and m is 1 -81- A slurry of Example (i)-a B (1 equivalent) and the appropriate aldehyde (B-CHO, 1.2 equivalents) in dichloromethane (20 mL) was treated with a catalytic amount of p-toluenesulfonic acid monohydrate (0.01 equivalents), stirred at room temperature for 30 minutes, treated with sodium triacetoxyborohydride (1.5 equivalents), stirred for 12 hours, diluted with dichloromethane, washed with brine, dried (Na 2 SO4), and concentrated. The residue was purified by HPLC with 10% acetone/90% hexanes to provide the desired compounds. Example (vii)-a Compounds of Formula I where Rj ^ and R2 are CF2; R9 is H: Z is carbon: O is 1.4-disubstituted phenyl: R _and Rs are hydrogen: L2 is -(alkylene NRfr-. R is hydrogen, and m is 1 and Example (viii)-a Compounds of Formula I where R and R2 are CF : R2 is H: Z is carbon: Q is 1 ,4-disubstituted phenyl: R 4 _and Rs are hydrogen: L2 is -C(H)=N- Example (vii)-a A Example (v)-a A (1 equivalent) in toluene at -78 °C was treated with DIBAl-H (1.5 M solution in toluene, 1.1 equivalent), stirred for 30 minutes, treated with water, warmed to room temperature, treated with 2 M sodium hydroxide, stirred for 30 minutes, and extracted with diethyl ether. The extract was washed with brine, dried (MgSO 4 ) and concentrated. The residue was passed through a silica gel plug (70-230 mesh, 100 mL) with 20% acetone/hexanes then purified by normal phase HPLC with 20% acetone/hexanes to provide the desired compound. *H NMR (300 MHz, DMSO-d 6 ) δ 10.10 (s, IH), 8.20-8.10 (m, 2H), 7.90 (d, 2H), 7.85 (s, IH); MS (DCI/NH 3 ) 308 (M+NH 4 -H 2 O)+. Example (vii)-a and Example (viii)-a (Method 13) Compounds of Formula I -82- A mixture of Example (vii)-a A (1 equivalent) and the appropriate amine (B-NH 2 , 1.1 equivalent) in dichloroethane (3 mL) at room temperature was treated sequentially with acetic acid (1.0 equivalent) and sodium triacetoxyborohydride (1.5 equivalents), shaken for 4 hours at room temperature, washed with brine, eluted through a MgSO 4 /silica gel plug with 10% acetone/hexanes, concentrated, and purified on silica gel with 10% acetone/hexanes to provide a mixture of the desired compounds. Example (ix)-a Compounds of Formula I where Rj ^ and R are CF2: R2 is H: Z is carbon: Q is 1 ,4-disubstituted phenyl: R4_and Rs are hydrogen: L is alkenylene Example (ix)-a A A solution of halide (B-Br where B is -Cg alkyl substituted with substituted aryl, 1 equivalent) and triphenylphosphine (1.2 equivalents) in toluene was heated to reflux for 2 hours, filtered, washed with toluene and dried under vacuum to provide the desired compounds. Example (ix)-a Compounds of Formula I (Method 14) A solution of sodium methoxide (prepared by the addition of sodium metal (1.06 equivalents) in methanol) was treated with Example (ix)-a A (1.0 equivalents) stirred at room temperature for 30 minutes, treated with Example (vii)-a A (1 equivalent), heated to reflux for 2 hours, cooled, treated with brine and extracted with diethyl ether. The extract was dried (Na 2 SO4), and concentrated. The residue was purified by HPLC eluting with acetone/hexanes to provide the desired compounds as a mixtures of Z (major) and E (minor) isomers. Example (x)-a Compounds of Formula I where R and R2 are CF2: R2 is H: Z is carbon: Q is 1.4-disubstituted phenyl: R S hydrogen: Rs_is alkoxycarbonyl: L2 is -N(RA)C(W)-: W is O: RA is hydrogen Example (x)-a A 2-Fluoro-5-nitrobenzoic acid in 3: 1 methanol/THF at 0 °C was treated dropwise with (trimethylsilyl)diazomethane to a yellow endpoint, stirred for 36 hours at room temperature, -83- treated with acetic acid, and concentrated. The residue was dissolved in ethyl acetate, washed with 2M sodium hydroxide, dried (Na 2 SO4), and concentrated to provide the desired compound. Example (x)-a B A slurry of sodium hydride (1 equivalent) in DMF was treated sequentially with N- 3,5-bis(trifluoromethyl)pyrazole (1 equivalent) in DMF and Example (x)-a A (1 equivalent) in DMF, heated to 45 °C for 10 hours, cooled to room temperature, treated with water, and extracted with ethyl acetate. The extract was washed with IM HCl, dried (Na 2 SO4), and concentrated. The residue was purified on silica gel with 20-70% ethyl acetate/hexanes to provide the desired compound. 1H NMR (300 MHz, DMSO-d 6 ) δ 8.76-8.64 (m, 2H) 8.17 (d, IH), 7.94 (s, IH), 3.70 (s, 3H). Example (x)-a C Example (x)-a B was processed by Method 3 to provide the desired compound, mp 45-47 °C; 1H NMR (300 MHz, DMSO-d 6 ) δ 7.6 (s, IH), 7.20 (d, IH), 7.13 (d, IH), 6.76 (dd, IH), 5.92 (s, 2H), 3.46 (s, 3H). Example (x)-a Compounds of Formula I Example (x)-a C was processed by Method 5, 6, or 7 to provide the desired compounds of Formula I. Example (xi)-a Compounds of Formula I where R^ and R2 are CF2: R2 is H: Z is carbon: Q is 1.4-disubstituted phenyl: R4 S hydrogen: Rs_is CF2: L2 is -N(RA)C(W)-: W is O: RA is hydrogen Example (xi)-a A 4-Bromo-3-trifluoromethylnitrobenzene was processed as in Example (x)-a B to provide the desired compound. Example (xi)-a B Example (x)-a A was processed by Method 3 to provide the desired compound. -84- ! H NMR (DMSO-d 6 , 300 MHz) δ 7.78 (s, IH), 7.4 (d, IH), 7.03 (d, IH), 6.84 (dd, IH), 6.25 (s, 2H). Example (xi)-aCompounds of Formula I Example (xi)-a B was processed by Method 5, 6, or 7 to provide the desired compounds of Formula I. Example (xii)-a Compounds of Formula I where R^ and R are CF : R? is H; Z is carbon: Q is 1.4-disubstituted phenyl: R 4 S hydrogen: Rs_is CF : L is -N(RA)C(W)-; W is O: RA is hydrogen Example (xii)-a A 4-Fluoro-2-trifluoromethylnitrobenzene was processed as in Example (x)-a B to provide the desired compound. Example (xii)-a B Example (xii)-a A was processed by Method 3 to provide the desired compound. *H NMR (DMSO-d 6 , 300 MHz) δ 7.75 (s, IH), 7.6 (d, IH), 7.46 (dd, IH), 6.95 (d, IH), 6.22 (s, 2H). Example (xii)-aCompounds of Formula I Example (xii)-a B was processed by Method 5, 6, or 7 to provide the desired compounds of Formula I. Example (xiii)-a Compounds of Formula I where R \ and R2 are CF2: R2 is H: Z is carbon: O is 1.4-disubstituted phenyl: R S hydrogen: Rs_is halo: L is -N(RA)C(W)-: W is O: RA is hydrogen Example (xiii)-a A 4-Bromo-3-chloronitrobenzene was processed as in Example (x)-a B to provide the desired compound. -85- Example (xiii)-a B Example (xiii)-a A was processed by Method 3 to provide the desired compound. IH NMR (DMSO-d 6 , 300 MHz) δ 7.76 (s, IH), 7.32 (d, IH), 6.8 (d, IH), 6.1 (dd, IH), 6.04 (s, 2H). Example (xiii)-aCompounds of Formula I Example (xiii)-a B was processed by Method 5, 6, or 7 to provide the desired compounds of Formula I. Example (xiv)-a Compounds of Formula I where R^ and R2 are CF2: R2 is H: Z is carbon: Q is 1.4-disubstituted phenyl; R4 S hydrogen; Rs_is methyl: L is -N(RA)C(W)-: W is O: RA is hydrogen Example (xiv)-a A 4-Fluoro-2-methylnitrobenzene was processed as in Example (x)-a B to provide the desired compound. Example (xiv)-a B Example (xiv)-a A was processed by Method 3 to provide the desired compound. J H NMR (DMSO-d 6 , 300 MHz) δ 7.68 (s, IH), 7.1 (d, IH), 7.06 (dd, IH), 6.68 (d, IH), 5.4 (s, 2H), 2.08 (s, 3H). Example (xiv)-aCompounds of Formula I Example (xiv)-a B was processed by Method 5, 6, or 7 to provide the desired compounds of Formula I. Example (xy)-a Compounds of Formula I where R_^ and R2 are CF2: R2 is H: Z is carbon: Q is 1.4-disubstituted phenyl: R4 1S hydrogen: Rs_is alkoxy: L 2 is -N(RA)C(W)-: W is O: RA is hydrogen Example (xy)-a A -86- 4-Fluoro-2-methoxynitrobenzene was processed as in Example (x)-a B and purified by flash chromatography on silica gel with 1:70:30 ethyl acetate/pentane/dichloromethane to provide the desired compound. Example (xy)-a B Example (xv)-a A was processed by Method 3 to provide the desired compound. J H NMR (DMSO-d 6 , 300 MHz) δ 7.73 (s, IH), 6.99 (d, IH), 6.85 (dd, IH), 6.7 (d, IH, 3.88 (s, 3H). Example (xy)-aCompounds of Formula I Example (xv)-a B was processed by Method 5, 6, or 7 to provide the desired compounds of Formula I. Example (xyi)-a Compounds of Formula I where Rj ^ and R2 are CF : R2 is H: Z is carbon: O is 1.4-disubstituted phenyl: R 4 _is hydrogen: Rs_is halo: L is -N(RA)C(W)-: W is O: RA is hydrogen and Example (xyii)-aRj_ and R are CF2: R2 is H: Z is carbon: O is 1 ,4-disubstituted phenyl: R S hydrogen: Rs_is substituted heterocycle: L2 is -N(RA)C(W)-: W is O: RA is hydrogen Example (xyi)-a A and Example (xyii)-a A 2,4-Difluoronitrobenzene was processed as in Example (x)-a B to provide a mixture of the desired compounds. Example (xyi)-a B and Example (xyii)-a B Examples (xvi)-a A and Example (xvii)-a A were processed by Method 3 to provide a mixture the desired compounds. J H NMR (DMSO-d 6 , 300 MHz) (mixture of (xvi)-a B and (xvii)-a B ) (xvi)-a B: δ 7.74 (s, IH), 7.19 (m, 2H), 6.84 (dd, IH), 5.18 (s, 2H) and (xvii)-a B: δ 7.74 (s, IH), 7.72 (s, IH), 7.52 (d, IH), 7.48 (dd, IH), 6.94 (d, IH), 5.95 (s, 2H). Example (xyi)-a and Example (xyii)-a Compounds of Formula I -87- Example (xvi)-a B and Example (xvii)-a B were processed by Method 5, 6, or 7 to provide a mixture the desired compounds of Formula I which were separated by column chromatography. (xyiii)-a Compounds of Formula I where R^ is CH : R ? is H: R is CF2: Z is carbon: Q is 1.4-disubstituted phenyl: R 4 _and Rs are hydrogen: L is -N(RA)C(W)-: W is O: and RA is H and (xix)-a Rl is CF : R2 is H: R2 is CH2: Z is carbon; Q is 1 ,4-disubstituted phenyl: R 4 _and Rs are hydrogen: L2 is -N(RA)C(W)-: W is O: and RA is H Example (xyiii)-a A and Example (xix)-a A A solution of 4-nitrophenylhydrazine (5 g, 32.5 mmol) and l,l,l-trifluoro-2,4- pentanedione (4.97 g, 32.5 mmol) in ethanol (200 mL) was treated with concentrated sulfuric acid (1 mL), refluxed for 1 hour, and concentrated. The residue was dissolved in ethyl acetate, washed with water and brine, dried (MgSO 4 ), and concentrated. The residue was purified on silica gel eluting with 3.5% ethyl acetate/pentane to provide the desired compounds. (xviii)-a A: ] H NMR (DMSO-d 6 , 300 MHz) δ 8.42 (d, 2H), 7.9 (d, 2H), 7.1 (s, IH), 2.33 (s, 3H) and (xix)-a A: *H NMR (DMSO-d 6 , 300 MHz δ 8.42 (d, 2H), 7.94 (d, 2H), 6.88 (s, IH), 2.46 (s, 3H). Example (xyiii)-a B A solution of Example (xviii)-a A was processed by Method 3 to provide the desired compound. ! H NMR (DMSO-d 6 , 300 MHz) δ 7.05 (d, 2H), 6.77 (s, IH), 6.62 (d, 2H), 2.24 (s, 3H). Example (xix)-a B Example (xix)-a A was processed by Method 3 to provide the desired compound. *H NMR (DMSO-d 6 , 300 MHz) δ 7.13 (d, 2H), 6.65 (s, IH), 6.64 (d, 2H), 5.48 (s, IH), 2.24 (s, 3H). -88- (xyiii)-a Compounds of Formula I and (xix)-a Compounds of Formula I Example (xviii)-a B and Example (xix)-a B were each processed by Method 5, 6, or 7 to provide the desired compounds of Formula I. (xx)-a Compounds of Formula I where R^ is CH : R2 and R2 are H: Z is carbon: O is 1 ,4-disubstituted phenyl: R _and Rs are hydrogen: L 2 is -N(RA)C(W)-: W is O: and RA is H and (xxi)-a Rj ^ and R? are H: R is CH : Z is carbon: O is 1.4-disubstituted phenyl: R4_and Rs are hydrogen: L is -N(RA)C(W)-: W is O: and RA is H Example (xx)-a A and (xxi)-a A 4-Nitrophenylhydrazine and acetylacetaldehyde dimethylacetal were processed as in Example (xviii)-a A/Example (xix)-a A and purified by flash chromatography on silica gel with 0.5:5:5 ethyl acetate/dichloromethane/pentane to provide the desired compounds. (xx)-a A: J H NMR (CDC1 3 , 500 MHz) δ 8.32 (d, 2H), 7.93 (d, IH), 7.84 (d, 2H), 6.36 (d, IH), 2.4 (s, 3H) and (xxi)-a A: ] H NMR (CDC1 3 , 500 MHz) δ 8.36 (d, 2H), 7.73 (d, 2H), 7.64 (d, IH), 6.28 (d, IH), 2.48 (s, 3H). Example (xx)-a B Example (xx)-a A was processed by Method 3 to provide the desired compound. *H NMR (CDC1 3 , 300 MHz) δ 7.68 (d, IH), 7.05 (d, 2H), 6.75 (d, 2H), 6.20 (d, IH), 2.38 (s, 3H). Example (xxi)-a B Example (xxi)-a A was processed by Method 3 to provide the desired compound. l H NMR (DMSO-d 6 , 300 MHz) δ 7.42 (s, IH), 7.08 (dd, 2H), 6.62 (dd, 2H), 6.17 (s, IH), 5.3 (br s , 2H), 2.22 (s, 3H). -89- (xx)-a Compounds of Formula I and (xxi)-a Compounds of Formula I Example (xx)-a B and Example (xxi)-a B were each processed by Method 5, 6, or 7 to provide the desired compounds of Formula I. Example (xxii)-a Compounds of Formula I where Rj is CF2: R2 and R2 are H: Z is carbon: O is 1.4-disubstituted phenyl: R4_and Rs are hydrogen: L 2 is -N(RA)C(W)-: W is O: and RA is H Example (xxii)-a A A solution of 3-trifluoromethylpyrazole (1 g, 7.4 mmol) in DMF (10 mL) at 0 °C was treated with NaH (60% in oil, 382 mg, 9.6 mmol), stirred at room temperature for 30 minutes, treated with 4-fluoronitrobenzene (1.04 g, 7.4 mmol), stirred for 18 hours, treated with water, and extracted with ethyl acetate. The extract was washed with brine, dried (MgSU4) and concentrated. The residue was purified on silica gel with 9% ethyl acetate/pentane to provide the desired compound. J H NMR (DMSO-d 6 , 300 MHz) δ 8.9 (m, IH), 8.43 (d, 2H), 8.2 (d, 2H), 7.2 (d, IH). Example (xxii)-a B Example (xxii)-a A was processed by Method 3 to provide the desired compound. !H NMR (DMSO-d 6 , 300 MHz) δ 8.42 (m, IH), 7.45 (d, 2H), 6.92 (d, IH), 6.65 (d, 2H), 5.4 (m, 2H). Example (xxii)-a Compounds of Formula I Example (xxii)-a B was processed by Method 5, 6, or 7 to provide the desired compounds of Formula I. Example (xxiii)-a -90- Compounds of Formula I where R^ is CF : R9 is H: R is hydroxyl: Z is carbon: O is 1 ,4-disubstituted phenyl: R _and Rs are hydrogen: L2 is -N(RA)C(W)-: W is O: and RA is H Example (xxiii)-a A A solution of ethyl 4,4,4-trifluoroacetoacetate (10 g, 54 mmol) and 4- nitrophenylhydrazine (8.3 g, 54 mmol) in ethanol (200 mL) was treated with concentrated sulfuric acid (0.5 ml), refluxed for 25 minutes, and concentrated. The residue was dissolved in ethyl acetate, washed with brine, dried (MgSO 4 ), and concentrated to provide the desired compound. ] HNMR (CDC1 3 , 300 MHz) δ 9.8 (s, IH), 8.21 (d, 2H), 7.23 (d, 2H), 4.27 (q, 2H), 3.56 (s, 2H), 1.24 (t, 3H). Example (xxiii)-a B A solution of Example (xxiii)-a A (7.7 g. 24.2 mmol) in 2: 1 ethanol: dichloromethane (300 mL) was treated with anhydrous K 2 CO (6.7g, 48.4 mmol), stirred at room temperature for 18 hours, and concentrated. The residue was neutralized with dilute HCl, extracted with ethyl acetate, washed with brine, dried (MgSO4), and concentrated. The residue was flash chromatographed on silica gel with 5% methanol/dichloromethane to provide the desired compound. Η NMR (DMSO-d 6 , 300 MHz) δ 8.38 (d, 2H), 8.15 (d, 2H), 5.9 (s, IH). Example (xxiii)-a C Example (xxiii)-a B was processed by Method 3 to provide the desired compound. ! H NMR (DMSO-d 6 , 300 MHz) δ 7.24 (d, 2H), 6.62 (d, 2H), 5.85 (s, IH ), 5.4 (m, 2H). Example (xxiii)-a Compounds of Formula I Example (xxiii)-a C was processed by Method 5, 6, or 7 to provide the desired compounds of Formula I. Example (xxiv)-a Compounds of Formula I where -91- R^ and R2 are CF2: R2 is H: Z is carbon: O is 1 ,4-disubstituted pyridine: R _and Rs are hydrogen: L2 is -N(RA)C(W)- where W is O and RA is H Example (xxiv)-a A N-3,5-bis(trifluoromethyl)pyrazole was processed as in Example (x)-a B but substituting 2-chloro-5-nitropyridine for Example (x)-a A to provide the desired compound. l NMR (DMSO-d 6 , 300 MHz) δ 9.39 (d, IH), 8.88 (dd, IH), 8.21 (d, 2H), 8.02 (s, IH). Example (xxiv)-a B Example (xxiv)-a A was processed by Method 3 to provide the desired compound. l K NMR (DMSO-d 6 , 300 MHz) δ 7.82(d, IH), 7.72 (s, IH), 7.43 (d, IH), 7.14 (dd, IH), 5.90 (s, 2H). Example (xxiv)-a Compounds of Formula I Example (xxiv)-a B was processed by Method 5, 6, or 7 to provide the desired compounds of Formula I. Example (xxy)-a Compounds of Formula I where R and R are GHh: Z is nitrogen: O is 1 ,4-disubstituted phenyl: R4_and Rs are hydrogen: L2 is -N(RA)C(W)- where W is O and RA is H Example (xxy)-a A A solution of 4-nitrophenylhydrazine (2 g, 13.1 mmol) and diacetamide (1.32 g, 13.1 mmol) in ethanol (80 mL) was treated with concentrated sulfuric acid (0.5 mL), refluxed for 1 hour, and concentrated. The residue was dissolved in ethyl acetate, washed with water and brine, dried (MgSO 4 ) and concentrated. Purification of the residue by flash chromatography on silica gel with 3:2:5 ethyl acetate/pentane/dichloromethane provided the desired compound. i H NMR (DMSO-d 6 , 300 MHz) δ 8.4 (d, 2H) 7.9 (d, 2H), 2.54 (s, 3H), 2.33 (s, 3H). Example (xxy)-a B Example (xxv)-a A was processed by Method 3 to provide the desired compound. -92- ] H NMR (DMSO-d 6 , 300 MHz) δ 7.18 (d, 2H), 6.7 (d, IH), 5.45 (s, 2H), 2.35 (s, 3H), 2.27 (s, 3H). Example (xxv)-a Compounds of Formula I Example (xxv)-a B was processed by Method 5, 6, or 7 to provide the desired compounds of Formula I. Example 1 N- T4- [ " 3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyllcyclopropanecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 204-205 °C; MS (DCI/NH3) m e 381 (M+NH 4 )+; IH NMR (DMSO-d 6 , 300 MHz) δ 10.52 (s, IH), 7.79 (d, 2H), 7.78 (s, IH), 7.53 (d, 2H), 1.81 (m, IH), 0.85 (d, 4H). Example 2 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyn-2.2,3.3- tetramethylcyclopropanecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 171-172 °C; MS (DCI/NH3) m/e 437 (M+NH 4 )+; i H NMR (DMSO-d 6 , 300 MHz) δ 7.78 (s, IH), 7.77 (d, 2H), 7.5 (d, 2H), 1.33 (s, IH), 1.26 (s, 6H),1.2 (s, 6H). Example 3 N- [4- r3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllpheny 11 -2.2-dichloro- 1 - methylcyclopropanecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 143-145 °C; MS (ESI-) m/e 445 (M-H)-; -93- J H NMR (CDC1 3 , 300 MHz) δ 7.65 (d, 2H), 7.50 (d, 3H), 7.15 (s,lH), 2.35 (d, IH), 1.65 (s, 3H), 1.45 (d, IH). Example 4 N- 4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl1-2-oxo-6-pentyl-2H-pyran-3- carboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 140-141 °C; MS (DCI/NH 3 ) m/e 488 (M+H)+; IH NMR (DMSO-d 6 , 300 MHz) δ 8.4 (d, IH), 7.92 (d, 2H), 7.83 (s, IH), 7.62 (d, 2H), 6.62 (d, IH), 2.65 (t, 2H), 1.65 (m, 2H), 1.33 (m, 4H), 0.89 (t, 3H). Example 5 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazoI-l-yllphenyl1-3.5-difluorobenzenesulfonamide Example (i)-a B was processed as in Example (iii)-a (Method 9) to provide the title compound. MS (DCI/NH 3 ) m/e 489 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 11.19 (s, IH), 8.03-7.95 (m, IH), 7.79 (s, IH), 7.60-7.55 (m, IH), 7.52 (d, 2H), 7.33-7.29 (m, IH), 7.28 (d, 2H). Example 6 N- [4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl! - 1 -cyclohexene- 1 -carboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 146-148 °C; MS (ESI-) 402 (M-H)-; !H NMR (CDC1 3 , 300 MHz) δ 7.65 (d, 2H), 7.55 (br s, IH ), 7.45 (d, 2H), 7.05 ( s,lH), 4.78 (m, IH), 2.40-2.20 (m, 4H), 1.80-1.60 (m, 4H). Example 7 N-F4-r3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyll-2-methylcyclopropanecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. -94- mp 172-173 °C; MS (DCI/NH3) m/e 395 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 7.8 (s, IH), 7.78 (d, 2H), 7.54 (d, 2H), 1.57 (m, IH), 1.27 (m, IH), 1.12 (d, 3H), 1.05 (m, IH), 0.7 (m, IH); Example 8 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-5-(3,5-dichlorophenoxy)-2- furancarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 152-153 °C; MS (DCI/NH3) m/e 551 (M+H) + ; l H NMR (DMSO-d 6 , 300 MHz) δ 10.45 (s, IH), 7.95 (d, 2H), 7.82 (s, IH), 7.6 (d, 2H), 7.55 (t, IH), 7.47 (d, IH), 7.4 (d, 2H), 6.15 (d, IH). Example 9 N- 4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenylj - 1 -methyl-2-cyclohexene- 1 - carboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 108-110 °C; MS (ESI-) m/e 416 (M-H)-; J H NMR (CDCI 3 , 300 MHz) δ 7.70 (d, 3H), 7.43 (d, 2H), 7.05 (s, IH ), 5.90-5.65 (m, 2H), 2.63-2.45 (m, IH), 2.20-1.85 (m, 4H), 1.60-1.60 (m, IH), 1.25 (s, 3H). Example 10 N- 4- 3.5-bis(trifluoromethyl)- IH-pyrazol- 1 -yllphenyl]- 1 -cyclopentene- 1 -carboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 174-175 °C; MS (DCI/NH3) m/e 407 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 9.95 (s, IH), 7.90 (d, 2H), 7.79 (s, IH), 7.55 (d, 2H), 6.78 (m, IH), 2.64-2.46 (m, 4H), 1.93 (m, 2H). -95- Example 11 N-[4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-ynphenyl1-3-methoxycyclohexanecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 145-147 °C; MS (DCI/NH3) m/e 436 (M+H)+; ! H NMR (CDCI3, 300 MHz) (diasteromers) δ 7.85 (br s, IH), 7.70 (m, 4H), 7.45 (m, 4H), 7.35 (br s, IH ), 7.05 (s, 2H ), 3.65 (m, IH), 3.40 (s, 3H), 3.35 (s, 3H ), 3.26 (m, IH), 2.65 ( m, IH), 2.45 -2.25 (m, IH), 2.15-1.85 (m, 8H), 1.8-1.3 (m, 8H). Example 12 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-2-butynamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 220-221 °C; MS (DCI/NH3) m/e 379 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 7.82 (s, IH), 7.79 (d, 2H), 7.57 (d, 2H), 2.08 (s, 3H). Example 13 ethyl 3-rr r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyllaminolcarbonyllamino1- benzoate Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp 211-212 °C; MS (DCI/NH3) m/e 504 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 9.09 (s, IH), 8.46 (t, IH), 8.10 (s, IH), 7.98 (d, 4H), 7.95 (dt, IH), 7.84 (d, 2H), 4.68 (q, 2H), 1.67 (t, 3H). Example 14 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-3-furancarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 206-207 °C; MS (DCI/NH3) m/e 390 (M+H)+; -96- J H NMR (DMSO-d 6 , 300 MHz) δ 10.25 (s, IH), 8.43 (s, IH), 7.95 (d, 2H), 7.83 (s, 2H), 7.6 (d, 2H), 7.03 (s, IH). Example 15 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-2-methyl-3-nitrobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 194-195 °C; MS (DCI/NH 3 ) m/e 476 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.95 (s, IH), 8.04 (d, IH), 7.95 (d, 2H), 7.85 (d, IH), 7.82 (s, IH), 7.64 (d, 2H,), 7.6 (t, IH), 2.48 (s, 3H). Example 16 N- 4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-N'-(3-cyanophenyl)urea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp 204-205 °C; MS (DCI/NH3) m/e 457 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 9.24 (s, IH), 9.16 (s, IH), 7.98 (t, IH), 7.79 (s, IH), 7.73- 7.65 (m, 3H), 7.54 (d, 2H), 7.43 (dd, 2H). Example 17 N-[4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-l-hydroxycyclopropanecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 198-200 °C; MS (DCI/NH3) m/e 397 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.22 (s, IH), 7.98 (d, 2H), 7.81 (s, IH), 7.54 (d, 2H), 6.64 (s, IH), 1.19 (m, IH), 1.1 (t, 2H), 1.0 (m, IH). Example 18 N-r4r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyllcycloheptanecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. -97- mp 174-175 °C; MS (DCI) m/e 420 (M+H)+; l H NMR (DMSO-d 6 , 300 MHz) δ 10.15 (s, IH), 7.8 (s, IH), 7.8 (d, 2H), 7.52 (d, 2H), 1.4-1.9 (m, 13H). Example 19 N-[4-r3.5-bis(trifluoromethyl)- IH-pyrazol- l-yπphenyl ~ |-2-benzofurancarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 213-215 °C; MS (DCI/NH3) m e 440 (M+H)+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.87 (s, IH), 8.05 (d, 2H), 7.86 (s, IH), 7.85 (s, IH), 7.86 (d, IH), 7.76 (d, IH), 7.64 (d, 2H), 7.55 (t, IH), 7.4 (t, IH). Example 20 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-5-fluoro-lH-indole-2-carboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 253-255 °C; MS (DCI/NH3) m/e 457 (M+H)+; ] H NMR (DMSO-d 6 , 300 MHz) δ 11.95 (s, IH), 10.58 (s, IH), 8.03 (d, 2H), 7.64 (d, 2H), 7.84 (s, IH), 7.45-7.54 (m, 3H), 7.12 (dt, IH). Example 21 (E)-N-r4-r3.5-bis(trifluoromethyl)-lH-ρyrazol-l-yllphenvn-3-(2-chlorophenyl)-2- propenamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 173-175 °C; MS (DCI/NH 3 ) m/e 460 (M+H)+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.7 (s, IH), 7.94 (d, IH), 7.92 (d, 2H), 7.83 (s, IH), 7.81 (m, IH), 7.61 (d, 2H), 7.59 (m, IH), 7.47 (m, 2H), 6.93 (d, IH). Example 22 -98- 2-Benzoyl-N-[4-[3.5-bis(trifluoromethyl)- IH-pyrazol- 1-yllphenyllbenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 204-205 °C; MS (DCI/NH 3 ) m/e 521 (M+NH 4 )+; IH NMR (DMSO-d 6 , 300 MHz) δ 7.9 (d, 3H), 7.8 (s, IH), 7.69-7.57 (m, 2H), 7.53 (d, 2H), 7.42 (d, 2H), 7.35-7.22 (m, 4H). Example 23 3a(S)-(3aα.4β,6a )-N-f4-r3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyllhexahydro-2- oxo-lH-thieno[3,4-dlimidazole-4-pentanamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 185-186 °C; MS (ESI) m/e 522 (M+H)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.22 (s, IH), 7.8 (d, 2H), 7.79 (s, IH), 7.53 (d, 2H), 6.41 (s, IH), 6.33 (s, IH), 4.31 (m, IH), 4.15 (m, IH), 3.14 (m, IH), 2.83 (dd, IH), 2.59 (d, IH), 2.37 (t, 2H), 1.35-1.7 (m, 6H). 158406 Example 24 N-4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yll-N-(4-chlorophenyl)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 183-185 °C; 1H NMR (DMSO-d 6 , 300 MHz) δ 10.69 (s, IH), 8.23-8.10 (m, IH), 8.07-8.03 (m, 4H), 7.87 (s, IH), 7.86-7.72 (m, 4H); MS (DCI/NH 3 ) m/e 451(M+NH 4 ) + . Example 25 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl]-3-iodobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 192-193 °C; MS (DCI/NH 3 ) m/e 543 (M+NH 4 )+; -99- l H NMR (DMSO-d 6 , 300 MHz) δ 8.32 (dd, IH), 7.99 (d, 4H), 7.83 (s, IH), 7.62 (d, 2H), 7.37 (t, IH). Example 26 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1bicyclo 2.2.11hept-5-ene-2- carboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH3) m e 433 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.12 (s, IH), 7.80 (s, IH), 7.78 (d, 2H), 7.51 (d, 2H), 6.19 (dd, lH) 5.88 (dd, IH), 3.11-3.05 (m, IH), 2.89 (s, IH), 1.88-1.80 (m, IH), 1.43 (dd, IH), 1.34 (s, 2H). Example 27 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-2-methylcyclohexanecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH3) m/e 437 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.5 (s, IH), 7.8 (d, 2H), 7.8 (s, IH), 7.5 (d, 2H), 1.91 (m, 4H), 1.6-1.5 (m, 2H), 1.4-1.2 (m, 4H), 0.9 (d, 3H). Example 28 phenylmethyl P-[rr4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l- yllphenynamino " |carbonyl]propyπcarbamate Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 158-160 °C; MS (DCI/NH3) m e 515 (M+H)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.38 (s, IH), 7.82 (d, 2H), 7.8 (s, IH), 7.62 (d, IH), 7.55 (d, 2H), 7.3-7.4 (m, 5H), 5.05 (s, 2H), 4.0-4.14 (m, IH), 1.6-1.8 (m, 2H), 0.93 (t, 3H). Example 29 N-r4-r3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyll-3-cyclohexene-l -carboxamide -100- Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 177-178 °C; MS (DCI/NH 3 ) m/e 421 (M+NH 4 )+; i H NMR (DMSO-d 6 , 300 MHz) δ 7.91 (d, 2H), 7.88 (s, IH), 7.63 (d, 2H), 5.80 (s, 2H), 2.75 (m, IH), 2.35-2.20 (m, 2H), 2.22-1.97 (m, 2H), 2.05-1.99 (m, IH), 1.77-1.62 (m, IH). Example 30 4-f3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1-N-(4-fluorophenyl)benzamide Example (v)-a C was processed as in Example (v)-a (Method 11) to provide the title compound, mp 194-195 °C; MS (DCI/NH 3 ) m e 417 (M+H)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.58 (s, IH), 8.15 (d, 2H), 7.9 (s, IH), 7.81 (d, 2H), 7.8 (d, 2H), 7.23 (t, 2H). Example 31 N-[4-f3.5-bis(trifluoromethyl)- IH-pyrazol- l-yl1phenyl1-N'-(3-nitrophenyl)urea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound. mp 203-204 °C; MS (DCI/NH 3 ) m/e 477 (M+NH )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 9.42 (s, IH), 9.38 (s, IH), 8.58 (t, IH), 7.84 (d, IH), 7.80 (s, IH), 7.77 (d, IH), 7.70 (d, 2H), 7.60 (d, IH), 7.53 (d, 2H). Example 32 N- [4- T3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenylj -N'-(4-fluorophenyl)urea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound. mp 201-202 °C; MS (DCI/NH 3 ) m/e 450 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 9.50 (s, IH), 9.21 (s, IH), 8.19 (s, IH), 8.07 (d, 2H), 7.96- 7.83 (m, 4H), 7.55 (t, 2H). -101- Example 33 N- 4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-N'-[4-(trifluoromethyl)phenyl1urea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound. mp 210-212 °C; MS (DCI/NH 3 ) m/e 516 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 9.11 (s, IH), 9.01 (s, IH), 7.78 (s, IH), 7.67 (d, 2H), 7.59 (d, 2H), 7.53 (d, 2H), 7.31 (d, 2H). Example 34 N- 4- 3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyl1-N'-(3.5-dimethylphenyl)urea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp >230 °C; MS (DCI/NH 3 ) m/e 460 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 9.03 (s, IH), 8.66 (s, IH), 7.80 (s, IH), 7.65 (d, 2H), 7.50 (d, 2H), 7.09 (s, 2H), 6.65 (s, IH), 2.24 (s, 6H). Example 35 N-[ " 4-[3.5-bis(trifluoromethyl)- IH-pyrazol- 1-yllphenyll-l-methylcyclopropanecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 109-110 °C; MS(DCI/NH 3 ) m/e 395 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 9.47 (s, IH), 7.86 (d, 2H), 7.79 (s, IH), 7.53 (d, 2H), 1.43 (s, 3H), 0.92 (m, 2H), 0.68 (m, 2H). Example 36 N-r4-| " 3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyll-N'-phenylurea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp 185-187 °C; MS (DCI NH3) m/e 432 (M+NH 4 )+; -102- J H NMR (DMSO-d 6 , 300 MHz) δ 9.07 (s, IH), 8.81 (s, IH), 7.80 (s, IH), 7.66 (d, 2H), 7.52 (d, 2H), 7.49 (d, 2H), 7.30 (t, 2H), 7.00 (t, IH). Example 38 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyl]-N'-(3-chloro-2-methylphenyl)urea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp 193-196 °C; MS (DCI/NH3) m/e 480 (M+NH 4 )+; IH NMR (DMSO-d 6 , 300 MHz) δ 9.39 (s, IH), 8.28 (s, IH), 7.78 (s, IH), 7.72 (t, IH), 7.67 (d, 2H), 7.52 (d, 2H), 7.22- 7.15 (m, 2H), 2.31 (s, 3H). Example 39 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-N'-[4-(butyloxyphenyl)urea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp 193-196 °C; MS (DCI/NH3) m/e 504 (M+NH 4 )+; l NMR (DMSO-d 6 , 300 MHz) δ 9.10 (s, IH), 8.71 (s, IH), 7.91 (s, IH), 7.77 (d, 2H), 7.63 (d, 2H), 7.49 (d, 2H), 7.01 (d, 2H), 4.06 (t, 2H), 1.83-1.78 (m, 2H), 1.57-1.53 (m, 2H), 1.06 (t, 3H). Example 40 N-r4-| " 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-N'-(2-methyl-3-nitrophenyl)urea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp 235-236 °C; MS (DCI NH3) m/e 491 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 9.46 (s, IH), 8.46 (s, IH), 8.05 (dd, IH), 7.79 (s, IH), 7.68 (d, 2H), 7.60 (dd, IH), 7.54 (d, 2H), 7.43 (t, IH), 2.31 (s, 3H). Example 41 N- f 4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyll -N'-(2-chloro-4-nitrophenyl)urea -103- Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp 229-230 °C; MS (ESI-) m/e 492 (M-H)-; IH NMR (DMSO-d 6 , 300 MHz) δ 8.93 (s, IH), 8.56 (d, IH), 8.38 (d, IH), 8.14 (dd, IH), 7.80 (s, IH), 7.70 (d, 2H), 7.57 (d, 2H). Example 42 N-(4-acetylphenyl)-N'-r4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyllurea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp 230-231 °C; MS (DCI7NH 3 ) m/e 474 (M+NH 4 )+; IH NMR (DMSO-d 6 , 300 MHz) δ 9.26 (s, IH), 9.21 (s, IH), 7.93 (d, 2H), 7.81 (s, IH), 7.68 (d, 2H), 7.61 (d, 2H), 7.54 (d, 2H), 2.55 (S, 3H). Example 43 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-N'-(4-methyl-2-nitrophenyl)urea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound. mp 213-214 °C; MS (ESI-) m/e 472 (M-H) " ; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.13 (s, IH), 9.56 (s, IH), 8.14 (d, IH), 7.93 (d, IH), 7.81 (s, IH), 7.68 (d, 2H), 7.57-7.53 (m, 3H), 2.37 (s, 3H). Example 44 N- f4- r3 ■5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenylj -5-methyl-2-thiophenecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 200-202 °C; MS (DCI/NH 3 ) m/e 437 (M+NH 4 )+; iH NMR (DMSO-d 6 , 300 MHz) δ 8.0 (d, 2H), 7.9 (d, IH), 7.8 (s, IH), 7.6 (d, 2H), 7.0 (d, IH), 3.3 (s, 3H). -104- Example 45 N-[4- 3,5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-N'-(4-bromo-2.6- dimethylphenyPurea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp >230 °C; MS m/e (ESI-) m/e 519 (M-H)-; ! H NMR (DMSO-d 6 , 300 MHz) δ 9.20 (s, IH), 7.93 (s, IH), 7.79 (s, IH), 7.65 (d, 2H), 7.48 (d, 2H), 7.33 (s, IH), 2.22 (s, 6H). Example 46 N- f4- 3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyl]-4-( 1 H-pyrrol- 1 -yPbenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 249-252 °C; MS (DCI/NH 3 ) 482 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.58 (br s, IH), 8.04 (d, 2H), 8.01 (d, 2H), 7.81 (d, 2H), 7.80 (s, IH), 7.61 (d, 2H), 7.56 (t, 2H), 6.37 (t, 2H). Example 47 N- 4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyll-N'-heptylurea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp 129-130 °C; MS (DCI/NH3) m/e 454 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 7.58 (d, 2H), 7.45 (s, IH), 7.40 (d, 2H), 3.18 (t, 2H), 2.60 (quintet, 4H), 1.40-1.25 (m, 6H), 0.90 (t, 3H). Example 48 N- 4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-N'-(4-chloro-2-nitrophenyl)urea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp 225-227 °C; MS (DCI/NH3) m/e 511 (M+NH 4 )+; -105- ] H NMR (DMSO-d 6 , 300 MHz) δ 9.69 (s, IH), 8.30 (d, IH), 8.17 (d, IH), 7.82 (s, IH), 7.85- 7.78 (m, IH), 7.68 (d, 2H), 7.56 (d, 2H). Example 49 N-[4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-7-methoxy-2-benzofurancarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 109-110 °C; MS (DCI/NH3) m/e 487 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 8.0 (d, 2H), 7.8 (s, 2H), 7.6 (d, 2H), 7.4 (dd, IH), 7.3 (t, 1H), 7.1 (dd, IH), 4.0 (s, 3H). Example 50 N-f4- \3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyll-N'-2-methyl-5-nitrophenyl)urea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp >235 °C; MS (DCI/NH3) m e 473 (M+H)+; ] H NMR (DMSO-d 6 , 300 MHz) δ 9.62 (d, IH), 8.91 (d, IH), 8.40 (s, IH), 7.84 (dd, IH), 7.78 (s, IH), 7.70 (d, 2H), 7.55 (d, 2H), 7.50 (d, IH), 2.40 (s, 3H). Example 51 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-3-(hydroxymethyl)benzamide Example 129 was reduced with DIBAL-H as described in Example 107 to provide the title compound, mp 160-162 °C; MS (DCI/NH3) m/e 447 (M+NH 4 ) + ; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.57 (s, IH), 8.01 (d, 2H), 7.93 (s, IH), 7.85 (d, IH), 7.81 (s, IH), 7.6 (d, 2H), 7.57 (d, IH), 7.5 (t, IH), 5.35 (t, IH), 4.6 (d, 2H). Example 52 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyn-2-cyanoacetamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. -106- mp 140-143 °C; MS (DCI/NH3) m/e 380 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.6 (s, IH), 7.8 (s, IH), 7.7 (d, 2H), 7.6 (d, 2H), 4.0 (s, 2H). Example 53 N- [4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyll-2-cyclohexane- 1 -carboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 126-128 °C; MS (DCI/NH3) m/e 421 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.3 (br, s, IH), 7.8 (s, IH), 7.8 (d, 2H), 7.6 (d, 2H), 5.7 (s, 2H), 2.6 (m, IH), 2.2 (m, 2H), 2.1 (m, 2H), 1.9 (m, IH), 1.5 (m, IH). Example 54 N- 4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyll-4-methylcyclohexanecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH3) m/e 437 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 12.0 (br, s, IH), 7.8 (d, 2H), 7.8 (s, IH), 7.5 (d, 2H), 2.4 (t, IH), 1.9 (m, 4H), 1.4 (m, 4H), 1.3 (m, IH), 0.9 (d, 3H). Example 55 N-r4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-α-methoxy- - (trifluoromethyl)benzeneacetamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 127-129 °C; MS (DCI/NH3) m/e 529 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 8.0 (d, 2H), 7.8 (s, IH), 7.6 (m, 4H), 7.5 (m, 3H), 3.6 (s, 3H). Example 56 N-r4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyllheptanamide -107- Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 88-90 °C; MS (DCI/NH3) m/e 425 (M+NH 4 )+; Ϊ H NMR (DMSO-d 6 , 300 MHz) δ 10.2 (s, IH), 7.8 (s, IH), 7.8 (d, 2H), 7.6 (d, 2H), 2.4 (t, 2H), 1.6 (t, 2H), 1.3 (m, 6H), 0.9 (t, 3H). Example 57 N- [4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyll-2-phenoxybenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 108-109 °C; MS (DCI/NH3) m/e 509 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.7 (s, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.7 (dd, IH), 7.6-7.5 (m, 3H), 7.4-7.3 (m, 3H), 7.2-7.1 (m, 3H), 7.0 (d, IH). Example 58 3-Aιmno-N-[4-f3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyl]benzamide Example 58 was prepared from Example 140 using a procedure analogous to that described for Example 59. mp 203-204 °C; MS (DCI/NH3) m e 432 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 7.98 (d, 2H), 7.80 (s, IH), 7.58 (d, 2H), 7.18 (t, IH), 7.13- 7.07 (m, 2H), 6.80-6.74 (m, IH), 5.34 (s, 2H). Example 59 4- Amino-N- [4-T3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl1phenyl]benzamide To 15 mL of ethyl acetate and 100 mg of Example 93 was added 8 mg of 10% palladium on carbon catalyst under a nitrogen atmosphere. The mixture was stirred under hydrogen at room temperature for 20 hours, filtered and concentrted to provide a brown oil. The oil was chromatographed on silica gel with ethyl acetate/hexanes (20:80 then 30:70) to provide the title compound as a yellow oil. mp >240 °C; MS (DCI/NH3) m/e 415 (M+H)+; -108- ! H NMR (DMSO-d 6 , 300 MHz) δ 7.97 (d, 2H), 7.83 (s, IH), 7.75 (d, 2H), 7.55 (d, 2H), 6.62 (d, 2H), 5.84 (s, 2H). Example 60 4- Azido-N- \4- [3.5 -bis(trifluoromethy 1) - 1 H-pyrazol - 1 -y 11 phenyl 1 benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 182-184 °C; MS (DCI/NH3) m/e 458 (M+NH 4 )+; I H NMR (DMSO-d 6 , 300 MHz) δ 10.6 (s, IH), 8.1 (d, 2H), 8.0 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.3 (d, 2H). Example 61 N-[4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yll-2-thiopheneacetamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 181-183 °C; MS (DCI/NH3) m/e 437 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.6 (s, IH), 7.8 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.4 (dd, IH), 7.0 (m, 2H), 3.9 (s, 2H). Example 62 ^[S.S-bisdrifluoromethyD-lH-pyrazol-l-yllphenyll-l-tricyclop.S.l. ^l-decanecarboxmide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 213-214 °C; MS (DCI/NH3) m/e 475 (M+NH 4 )+; i H NMR (DMSO-d 6 , 300 MHz) δ 9.4 (s, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.5 (d, 2H), 2.1 (s, 3H), 1.9 (s, 6H), 1.7 (s, 6H). Example 63 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-N 2 -[(l.l-dimethylethoxy)carbonyn- L-asparagine. phenylmethyl ester -109- Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 195-196 °C; MS (DCI/NH 3 ) m/e 601 (M+NH 4 )+; 2 H NMR (DMSO-d 6 , 300 MHz) δ 10.4 (s, IH), 7.8 (s, IH), 7.8 (d, 2H), 7.4 (d, 2H), 7.3 (m, 5H), 5.1 (s, 2H), 4.5 (m, IH), 2.9 (m, IH), 2.7 (m, IH), 1.4 (s, 9H). Example 64 1.1-dimethylethyl r7-r[4-r3.5-bis(trifluoromethyl)- IH-pyrazol- l-yl1phenyl]aminol-7- oxoheptyllcarbamate Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 86-88 °C; MS (DCI/NH3) m/e 540 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 7.9 (s, IH), 7.9 (d, 2H), 7.5 (d, 2H), 3.3 (m, 12H), 1.2 (s, 9H). Example 65 N-f4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-3-(methylthio)propanamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 122-123 °C; MS (DCI/NH3) m/e 415 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.4 (s, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 2.9 (t, 2H), 2.7 (t, 2H), 2.2 (s, 3H). Example 66 N- 4-r3.5-bis(trifluoromethyl)- IH-pyrazol- 1-yllphenyll- 1-naphthylenecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 170-171 °C; MS (DCI/NH 3 ) m/e 467 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 11.0 (s, IH), 8.2 (m, IH), 8.1 (d, IH), 8.0 (m, 3H), 7.8 (d, IH), 7.8 (s, IH), 7.6 (m, 5H). -110- Example 67 N- 4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyl] -4-cy anobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 169-171 °C; MS (DCI/NH 3 ) m/e 442 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.8 (s, IH), 8.2 (d, 2H), 8.1 (d, 2H), 8.0 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H). Example 68 N-[4-r3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyll-2-phenylcyclopropanecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 176-178 °C; MS (DCI/NH 3 ) m/e 457 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.6 (s, IH), 7.8 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.3 (m, 2H), 7.2 (m, 3H), 2.4 (m, IH), 2.1 (m, IH), 1.6 (m, IH), 1.4 (m, IH). Example 69 N-r4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyll-4-iodobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 196-198 °C; MS (DCI/NH 3 ) m e 543 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.6 (s, IH), 8.0 (d, 2H), 7.9 (d, 2H), 7.8 (s, IH), 7.7 (d, 2H), 7.6 (d, 2H). Example 70 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyn-3-chloropropanamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 144-145 °C; MS (DCI/NH 3 ) m e 403 (M+NH 4 )+; -111- ! H NMR (DMSO-d 6 , 300 MHz) δ 10.4 (s, IH), 7.8 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 3.9 (t, 2H), 2.9 (t, 2H). Example 71 N- [4-[3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl1phenyl]-4-methoxybenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 205-207 °C; MS (DCI/NH 3 ) m/e 447 (M+NH 4 )+ ; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.5 (s, IH), 8.1 (d, IH), 8.0 (d, 2H), 7.9 (s, IH), 7.6 (d, 2H), 7.2-7.1 (m, 3H), 3.4 (s, 3H). Example 72 N- r4-f3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -ynphenyll-2-ethylhexanamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 127-128 °C; MS (DCI/NH 3 ) m/e 439 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.2 (s, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.5 (d, 2H), 2.3 (m, IH), 1.6-1.2 (m, 8H), 0.9 (m, 6H). Example 73 N- \4- 3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenylj -4-hydroxybenzamide Example 71 was treated with BBr 3 as described in Example 180B to provide the title compound, mp >245 °C; MS (DCI/NH 3 ) m/e 433 (M+NH 4 )+ ; ! H NMR (DMSO-d 6 , 300 MHz) δ 8.0 (d, 2H), 7.9 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 6.8 (d, 2H). Example 74 N-f4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyn-4-(hexyloxy)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. -112- mp 153-155 °C; MS (DCI/NH 3 ) m/e 517 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.4 (s, IH), 8.0 (m, 4H), 7.8 (s, IH), 7.6 (d, 2H), 7.1 (d, 2H), 4.1 (t, 2H), 1.8-1.7 (m, 2H), 1.5-1.4 (m, 2H), 1.4-1.3 (m, 4H), 0.9-0.8 (m, 3H). Example 75 N- -[3.5-bis(trifluoromethyl)-lH-pyrazol-l-ynphenyll-3-methylbenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 137-139 °C; MS (DCI/NH 3 ) m/e 431 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.5 (s, IH), 8.0 (d, 2H), 7.9 (s, IH), 7.8 (m, 2H), 7.6 (d, 2H), 7.4 (dd, 2H), 2.4 (s, 3H). Example 76 2-(Acetyloxy)-N- 4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyllbenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 159-161 °C; MS (DCI/NH 3 ) m/e 475 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.7 (s, IH), 8.0 (d, 2H), 7.9 (s, IH), 7.8 (dd, IH), 7.6 (d, 2H), 7.4 (m, IH), 7.3 (dd, IH), 2.2 (s, 3H). Example 77 N-[4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-N'-(4-bromo-2-methylphenyl)urea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp 230-231 °C; MS (DCI/NH 3 ) m/e 474 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 9.26 (s, IH), 9.21 (s, IH), 7.93 (d, 2H), 7.81 (s. IH), 7.68 (d, 2H), 7.61 (d, 2H), 7.54 (dd, IH), 2.55 (S, 3H). Example 78 N-r4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-2.4.6-trimethylbenzamide -113- Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 203-205 °C; MS (DCI/NH 3 ) m/e 459 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.7 (s, IH), 8.0 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 6.9 (s, 2H), 2.3 (s, 3H), 2.2 (s, 6H). Example 79 N- [4- 3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyl] -N'-(4-chloro-3-nitrophenyl)urea Example (i)-a B was processed as in Example (ii)-a (Method 8) to provide the title compound, mp 207-209 °C; MS (ESI-) m/e 492 (M-H)-; Η NMR (DMSO-d 6 , 300 MHz) δ 9.42 (s, IH), 9.32 (s, 1H),8.33 (t, IH), 7.81 (s, IH), 7.72- 7.63 (m, 4H), 7.55 (d, 2H). Example 80 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-2-chloro-N-methylbenzamide Example 91 was processed as in Example (iv)-a (Method 10) to provide the title compound. MS (DCI NH3) m/e 465 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 100 °C, 300 MHz) δ 7.58 (s, IH), 7.47 (s, 4H), 7.40-7.23 (m, 4H), 3.38 (s, 3H). Example 81 N- 4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyll-2-chloro-4-nitro-N-methylbenzamide N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-2-chloro-4-nitrobenzamide was processed as Example (i)-a in Example (iv)-a (Method 10) to provide the title compound. MS (DCI NH3) m/e 510 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 8.10-8.02 (m, 2H), 7.44-7.36 (m, 3H), 7.28 (d, 2H), 7.06 (s, IH), 3.61 (s, 3H). Example 82 N- \4- ( " 3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljpheny 11 -2-chlorobenzenemethanamine -114- Example (i)-a B was processed as in Example (vi)-a (Method 12) to provide the title compound, mp 240 °C; MS (DC17NH 3 ) m/e 420 (M+H)+; IH NMR (DMSO-d 6 , 300 MHz) δ 7.70 (s, IH), 7.54-7.47 (m, IH), 7.45-7.41 (m, IH), 7.38- 7.32 (m, 2H), 7.25 (d, 2H), 6.90 (t, IH), 6.67 (d, 2H), 4.40 (d, 2H). Example 83 N- 4-[3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyll- 1 -methyl-5-nitro- 1 H-pyrazole-4- carboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 214-216 °C; MS (DCI/NH 3 ) m/e 466 (M+NH 4 )+; IH NMR (DMSO-d 6 , 300 MHz) δ 10.83 (s, IH), 8.03 (s, IH), 7.89 (d, 2H), 7.87 (s, IH), 7.63 (d, 2H). Example 84 N-r4-| " 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-4-fluorobenzenemethanamine Example (i)-a B was processed as in Example (vi)-a (Method 12) to provide the title compound, mp 92-94 °C; MS (DCI/NH 3 ) m/e 404 (M+H)+ and 421 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 7.68 (s, IH), 7.45-7.38 (m, 2H), 7.24-7.13 (m, 4H), 6.87 (t, IH), 6.68 (d, 2H), 4.33 (d, 2H). Example 85 N- 4- r3.S-bisdrifluoromethyD- 1 H-pyrazol- 1 -yljpheny 11-4-bromobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 205-207 °C; MS (DCI/NH3) m/e 495 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.6 (s, IH), 8.0 (d, 2H), 7.9 (d, 2H), 7.8 (s, IH), 7.8 (d, 2H), 7.6 (d, 2H). -115- Example 86 N- [4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenylj -2-(dimethylamino)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCIZNH 3 ) m/e 441 (M+H)+; l NMR (CDC1 3 , 300 MHz) δ 8.1 (dd, IH), 7.85 (d, 2H), 7.51 (m, IH), 7.48 (d, 2H), 7.35 (t, 2H), 7.07 (s, IH), 2.87 (s, 6H). Example 88 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-3-(dimethylamino)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 180-181°C; MS (DCI/NH3) m/e 443 (M+H)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 8.00 (d, 2H), 7.82 (s, IH), 7.60 (d, 2H), 7.35 (t, IH), 7.24- 7.20 (m, 2H), 6.98-6.95 (m, IH), 2.98 (s, 6H). Example 89 N-r4-r3,5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-4-(trifluoromethyl)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 170-172 °C; MS (DCI/NH3) m/e 485 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.8 (s, IH), 8.2 (d, 2H), 8.0 (d, 2H), 7.9 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H). Example 90 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyl1-4-fluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 184-186 °C; MS (DCI/NH3) m/e 435 (M+NH 4 )+; -116- H NMR (DMSO-d 6 , 300 MHz) δ 10.6 (s, IH), 8.1 (m, 2H), 8.0 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.4 (m, 2H). Example 91 N- r 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-2-chlorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 155-157 °C; MS (DCI/NH3) m/e 451 (M+NH 4 )+; IH NMR (DMSO-d 6 , 300 MHz) δ 10.9 (s, IH), 8.0 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.6-7.4 (m, 4H). Example 92 N-r4-r3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyl]benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 177-178 °C; MS (DCI/NH3) m/e 417 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 8.0-7.9 (m, 4H), 7.6 (m, 3H), 7.5 (m, 3H). Example 93 N-[4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl]-4-nitrobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 185-188 °C; MS (DCI/NH3) m/e 462 (M+NH 4 )+; ! H NMR (CDCI3, 300 MHz) δ 8.42 (d, 2H), 8.08 (d, 2H), 7.99 (br s, IH), 7.85 (d, 2H), 7.56 (d, 2H), 7.09 (s, IH). Example 94 443 ,5-Bis(trifluoromethyl)- 1 H-pyrazol- 1 -yll-N-(4-fluorophenyl)benzenemethanamine Example (vii)-a A was processed as in Example (vii)-a (Method 13) to provide the title compound, mp 102-103 °C; -117- MS (DCI/NH3) m/e 421 (M+NH4)+; *H NMR (DMSO-d 6 , 300 MHz) δ 7.83 (s, IH), 7.57 (s, 4H), 6.9 (t, 2H), 6.55 (m, 2H), 6.3 (t, IH), 4.37 (d, 2H). Example 95 3-[4-[ [3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyllmethyl1aminolbenzonitrile Example (vii)-a A was processed as in Example (vii)-a (Method 13) to provide the title compound, mp 129-130 °C; MS (DCI NH3) m/e 428 (M+NH4)+; !H NMR (DMSO-d 6 , 300 MHz) δ 7.83 (s, IH), 7.57 (m, 4H), 7.45 (d, 2H), 7.4 (t, IH), 6.68 (d, 2H), 4.48 (d, 2H). Example 96 N-r4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-2-methylbenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 165-167 °C; MS (DCI/NH3) m/e 431 (M+NH 4 )+; IH NMR (DMSO-d 6 , 300 MHz) δ 10.67 (br s, IH), 7.96 (d, 2H), 7.82 (s, IH), 7.60 (d, 2H), 7.53 (m, 4H), 2.41 (s, 3H). Example 97 (E)-N-F4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenylmethylenel-2.4- difluorobenzenamine Example (vii)-a A was processed as in Example (viii)-a (Method 13) to provide the title compound as a byproduct with Example 108. MS (DCI/NH3) m/e 420 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 8.8 (s, IH), 8.2 (d, 2H), 7.9 (s, IH), 7.8 (d, 2H), 7.5-7.4 (m, 2H), 7.2 (m, IH). Example 98 N-[4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyn-3-4-dimethoxybenzamide -118- Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 189-191 °C; MS(DCI/NH 3 ) 477 (M+NH 4 )+; IH NMR (DMSO-d 6 , 300 MHz) δ 10.40 (br s, IH), 7.99 (d, 2H), 7.83 (s, IH), 7.67-7.55 (m, 3H), 7.12 (d, 2H), 3.86 (s, 3H), 3.85 (s, 3H). Example 99 N- [4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyllcyclopentanepropanamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 130-132 °C; MS (DCI NH3) 437 (M+NH 4 )+; IH NMR (DMSO-d 6 , 300 MHz) δ 10.24 (br s, IH), 7.80 (s, IH), 7.79 (d, 2H), 7.53 (d, 2H), 2.37 (t, 2H), 1.81-1.73 (m, 3H), 1.66-1.48 (m, 8H). Example 100 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-4-methylbenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 225-226 °C; MS (DCI/NH 3 ) 431 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.50 (br s, IH), 8.01 (d, 2H), 7.91 (d, 2H), 7.83 (s, IH), 7.61 (d, 2H), 7.37 (d, 2H), 2.40 (s, 3H). Example 101 N- 4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl]-3-(trifluoromethyl)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 143-145 °C; MS(DCI/NH 3 ) 485 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.80 (br s, IH), 8.30 (m, 2H), 8.01 (d, 2H), 7.99 (s, IH), 7.85-7.80 (m, 2H), 7.65 (d, 2H). -119- Example 102 N- 4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyH-3-methyl-2-butenamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 150-152 °C; MS (DCIXNH3) 395 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.08 (br s, IH), 7.76 (s, IH), 7.72 (d, 2H), 7.45 (d, 2H), 5.83 (s, IH), 2.09 (s, 3H), 1.81 (s, 3H). Example 103 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyIl-2-hydroxybenzamide Example 143 was treated with BBr 3 as described in Example 180B to provide the title compound, mp 173-175 °C; MS (DCI/NH 3 ) m/e 433 (M+NH 4 ) + ; *H NMR (DMSO-d 6 , 300 MHz) δ 11.5 (br s, IH), 10.6 (s, IH), 8.0-7.9 (m, 3H), 7.8 (s, IH), 7.6 (d, 2H), 7.4 (m, IH), 7.1-7.0 (m, 2H). Example 104 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-3-hydroxybenzamide Example 145 was treated with BBr3 as described in Example 180B to provide the title compound, mp 221-223 °C; MS (DCI/NH3) m/e 433 (M+NH 4 )+ ; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.5 (br s, IH), 9.8 (s, IH), 8.0 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.4-7.3 (m, 3H), 7.0 (m, IH). Example 105 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-2.4-dimethyl-5-thiazolecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 158-159 °C; MS (DCI/NH3) m/e 435 (M+NH 4 )+; -120- ] H NMR (DMSO-d 6 , 300 MHz) δ 10.42 (s, IH), 7.88 (d, 2H), 7.82 (s, IH), 7.60 (d, 2H), 2.68 (s, 3H), 2.57 (s, 3H). Example 106 N-[4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-3-pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 185-188 °C; MS (DCI/NH 3 ) m/e 401 (M+H)+; IH NMR (DMSO-d 6 , 300 MHz) δ 10.78 (br s, IH), 9.14 (d, IH), 8.80 (dd, IH), 8.32 (dt, IH,), 8.01 (d, 2H), 7.83 (s, IH), 7.65-7.58 (m, 3H). Example 107 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-4-(hydroxymethyl)benzamide To a solution of carboxylic acid methyl ester, Example 142, in toluene was added 1.2 equivalent of DIBAl-H (1.5 M solution in toluene) at -78 °C. After stirring at -78 °C for 1 h, 1 equivalent more of DIBAl-H was added to consume all the starting material. Then the reaction mixtured was quenched with methanol followed by IN NaOH. After stirring for 30 min, the reaction mixture was partitioned between ether and brine. The organic layer was separated, dried and concentrated to give crude material which was purified by normal phase HPLC (20:80, acetone: hexane). The desired product was collected in approximately 15% yield, mp 213-214 °C; MS (ESI-) m/e 428 (M-H)-; *H NMR (DMSO-d 6 , 300 MHz) δ 10.52 (s, IH), 8.01 (d, 2H), 7.96 (d, 2H), 7.81 (s, IH), 7.6 (d, 2H), 7.5 (d, 2H), 5.35 (t, IH), 4.6 (d, 2H). Example 108 4-13.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yll-N-(2.4-difluorophenyl)benzenemethanamine Example (vii)-a A was processed as in Example (vii)-a (Method 13) to provide the title compound and Example 97 as a byproduct. MS (DCI/NH3) m/e 422 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 7.8 (s, IH), 7.6 (s, 4H), 7.1 (m, IH), 6.8 (m, IH), 6.6 (m, IH), 6.2 (m, IH), 4.4 (d, 2H). -121- Example 109 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-ynphenyl1-4-(methylsulfonyl)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 216-218 °C; MS(DCI/NH 3 ) 495 (M+NH 4 ); ] H NMR (DMSO-d 6 , 300 MHz) δ 8.20 (d, 2H), 8.12 (d, 2H), 8.02 (d, 2H), 7.83 (s, IH), 7.64 (d, 2H), 3.35 (s, 3H). Example 110 N-r4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-2-iodobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 180-182 °C; MS(DCI/NH 3 ) 543 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.80 (br s, IH), 7.97 (d, IH), 7.93 (d, 2H), 7.83 (s, IH), 7.62 (d, 2H), 7.55-7.50 (m, 2H), 7.30-7.21 (m, IH). Example 111 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-4-heptybenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 143-145 °C; MS (DCI/NH3) 515 (M+NH 4 )+; i H NMR (DMSO-d 6 , 300 MHz) δ 10.51 (br s, IH), 8.01 (d, 2H), 7.94 (d, 2H), 7.85 (s, IH), 7.60 (d, 2H), 7.39 (d, 2H), 2.67 (t, 2H), 1.6 (m, 2H), 1.35-1.20 (m, 8H), 0.86 (t, 3H). Example 113 N-r4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyl1-2-furancarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 179-182 °C; MS (DCI NH3) m/e 407 (M+NH 4 )+; -122- ] H NMR (DMSO-d 6 , 300 MHz) δ 10.54 (br s, IH), 7.99 (d, 2H), 7.98 (d, IH), 7.83 (s, IH), 7.60 (d, 2H), 6.75-6.71 (m, IH). Example 114 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyn-2-fluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 188-190 °C; MS (DCI/NH3) 435 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.80 (br s, IH), 7.94 (d, 2H), 7.83 (s, IH), 7.71 (t, IH), 7.62 (d, 2H), 7.65-7.59 (m, IH), 7.36 (q, 2H). Example 115 N- 4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyll -N'-methy 1- 1.2-benzenedicarboxamide 2-[[[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]amino]carbonyl]benzoic acid (0.02 g, 0.045 mmol) in thionylchloride (1 mL) was heated to reflux for 3h. The excess thionylchloride was removed under reduced pressure. To the acid chloride (0.023 mmol) in CH 2 C1 2 ( 1 mL) was added methylamine hydrochloride (4.6 mg, 0.067 mmol) followed by triethylamine ( 0.019 mL, 0.14 mmol). After stirring at room temperature over night, the reaction mixture was diluted with ether and washed with IN HCl, saturated NaHCO3 and brine. The solvent was removed, and the crude material was purified on silica gel column, eluting with 20% acetone /hexane to give the title compound. MS (DCI/NH3) m/e 474 (M+NH 4 ) + ; ! H NMR (CDCI3, 300 MHz) δ 9.98 (s, IH), 7.98 (d, IH), 7.87 (d, 2H), 7.58 (m, 2H), 7.48 (m, 3H), 7.05 (s, IH), 6.18 (bs, IH), 3.01 (m, 3H). Example 116 N- 4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl]-4-pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 156-157 °C; MS (DCI/NH3) m/e 401 (M+H)+; -123- J H NMR (DMSO-d 6 , 300 MHz) δ 10.83 (br s, IH), 8.82 (d, 2H), 8.01 (d, 2H), 7.89 (d, 2H), 7.84 (s, IH), 7.65 (d, 2H). Example 117 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-4-chloro-2-nitrobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 163-166 °C; MS(DCI/NH 3 ) 496 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 11.10 (br s, IH), 8.57 (s, d IH), 8.37 (dd, IH), 7.92 (d, 3H), 7.84 (s, IH), 7.65 (d, 2H). Example 118 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-4-cinnolinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH3) m/e 452 (M+H)+; !H NMR (DMSO-d 6 , 300 MHz) δ 11.30 (br s, IH), 9.68 (s, IH), 8.63 (d, IH), 8.32 (d, IH), 8.11-7.98 (m, IH), 8.02 (d, 2H), 7.85 (s, IH), 7.70 (d, 2H). Example 119 4-Acetyl-N-| " 4- .5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyl1benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 203-204 °C; MS (DCI/NH3) m/e 459 (M+NH 4 )+ ; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.8 (s, IH), 8.1 (s, 4H), 8.0 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 2.6 (s, 3H). Example 120 1.1 -Dimethylethyl 4- [ [ 4- 3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyllamino] carbonyll - 1 -piperidinecarboxylate Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH 3 ) m/e 524 (M+NH 4 )+; -124- ! H NMR (DMSO-d 6 , 300 MHz) δ 10.29 (br s, IH), 7.84 (d, 2H), 7.73 (s, IH), 7.56 (d, 2H), 2.90-2.70 (m, 3H), 2.63-2.50 (m, 2H), 1.90-1.80 (m, 2H), 1.63-1.40 (m, 2H), 1.44 (s, 9H). Example 121 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-2-pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH 3 ) m/e 401 (M+H)+; J H NMR (DMSO-d 6 , 300 MHz) δ 11.03 (br s, IH), 8.78 (dd, IH), 8.21-8.07 (m, 2H), 8.16 (d, 2H), 7.83 (s, IH), 7.74-7.69 (m, IH), 7.63 (d, 2H). Example 122 N-r4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-ynphenyl1-4-(diethylamino)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH 3 ) m/e 471 (M+H)+; l K NMR (DMSO-d 6 , 300 MHz) δ 10.15 (br s, IH), 7.99 (d, 2H), 7.87 (s, IH), 7.83 (d, 2H), 7.56 (d, 2H), 6.74 (d, 2H), 3.43 (q, 4H), 1.13 (t, 6H). Example 123 N- r4-T3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyllcyclopentanecarboxmide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 165-168 °C; MS (DCI/NH3) m/e 409 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.22 (br s, IH), 7.80 (d, 2H), 7.80 (s, IH), 7.53 (d, 2H), 2.84-2.76 (m, IH), 1.89-1.54 (m, 8H). Example 124 N- [4- 3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyllcyclohexanecarboxmide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 171-173 °C; MS (DCI NH3) m e 423 (M+NH 4 )+; -125- ! H NMR (DMSO-d 6 , 300 MHz) δ 10.23 (br s, IH), 7.89 (d, 2H), 7.86 (s, IH), 7.60 (d, 2H), 2.48-2.41 (m, IH), 1.95-1.25 (m, 10H). Example 125 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-4-piperidinecarboxamide To a stirred solution of the Boc-amine, Example 120, (165 mg, 0.323 mmol) in methylene chloride (3.0 mL) was added trifluoroacetic acid (0.250 mL, 3.25 mmol). The resulting solution was stirred at 23 °C for 2 hours at which point the reaction mixture was poured into saturated sodium bicarbonate solution (50 mL). The aqueous layer was extracted with ethyl acetate (2 X 50 mL). The combined organics were dried over sodium sulfate and concentrated. The crude residue was purified by flash column chromatography using 95% methylene chloride/5% methanol. Concentration of the approriate fractions afforded 45 mg, 34% yield of Example 125 as a white solid, mp 156-159 °C; MS (DCIXNH3) m/e 407 (M+H)+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.20 (br s, IH), 7.81 (d, 2H), 7.80 (s, IH), 7.53 (d, 2H), 3.05-2.97 (m, 2H), 2.48-2.40 (m, 2H), 1.79-1.70 (m, 2H), 1.60-1.45 (m, 2H). Example 126 N-r4- 3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyl1-3-(methylsulfonyl)benzamide The procedure in J. Org. Chem. 1991, 56, 4974, hereby incoφorated by reference, was followed. Briefly, to a solution of Na 2 SO 3 (0.63 g, 5.0 mmol) and NaHCO 3 (1.26 g, 15 mmol) in water (5 mL) was slowly added 3-chlorosulfonylbenzoic acid (1.1 g, 5.0 mmol). The reaction mixture was heated to 75° C for 1 hours, and then chloroacetic acid (0.71 g, 7.5 mmol) was added, followed by NaOH (0.3 g, 7.5 mmol). The resulting mixture was heated to 105 °C for 24 hours. After cooling to room temperature, the reaction was diluted with water and acidified with IN HCl to pH 2.The solid was filtered, washed and dried to give 680 mg of the product in 75% yield. 1H NMR (DMSO-d 6 , 300MHz) δ 8.4 (s, IH), 8.25 (d, IH), 8.17 (d, IH), 7.8 (t, IH), 3.35 (s, 3H); MS (DCI NH3) m/e 218 (M+NH 4 )+. Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) with the benzoic acid prepared as described above to provide the title compound. -126- mp 194-195 °C; MS (DCI/NH 3 ) m/e 495 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 8.5 (s, IH), 8.32 (d, IH), 8.17 (d, IH), 8.0 (d, 2H), 7.86 (t, IH), 7.84 (s, IH), 7.65 (d, 2H), 3.3 (s, 3H). Example 127 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyl1-2-(trifluoromethyI)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 133-135 °C; MS (DCI/NH 3 ) m/e 485 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.86 (s, IH), 7.93-7.67 (m, 8H), 7.57 (d, IH). Example 128 3- 4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyllmethyllaminolbenzonitrile Example (vii)-a A was processed as in Example (vii)-a (Method 13) to provide the title compound. MS (DCI/NH 3 ) m/e 428 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 7.8 (s, IH), 7.6 (m, 4H), 7.2 (m, IH), 6.9 (m, 4H), 4.4 (d, 2H). Example 129 Methyl 3-[ " rr4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyllamino]carbonyllbenzoate Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 174-175 °C; MS (DCI/NH 3 ) m/e 475 (M+NH 4 )+; l K NMR (DMSO-d 6 , 300 MHz) 10.8 (s, IH), 8.56 (s, IH), 8.27 (d, IH), 8.2 (d, IH), 8.02 (d, 2H), 7.85 (s, IH), 7.73 (t, IH), 7.63 (d, 2H), 3.94 (s, 3H). Example 130 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-3-chlorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. -127- mp 142-144 °C; MS (DCI NH3) m/e 451 (M+NH 4 )+; l NMR (DMSO-d 6 , 300 MHz) δ 10.66 (s, IH), 8.05-7.87 (m, 5H), 7.82 (s, IH), 7.73-7.51 (m, 3H). Example 131 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-2-thiophenecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp >230 °C; MS (DCI/NH3) m/e 423 (M+NH 4 )+; } H NMR (DMSO-d 6 , 300 MHz) δ 10.54 (s, IH), 8.07 (d, IH), 7.95 (d, 2H), 7.90 (d, IH), 7.82 (s, IH), 7.62 (d, 2H), 7.26 (td, IH). Example 132 (E)-3-r2-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyllethenyllbenzonitrile Example (vii)-a A was processed as in Example (ix)-a (Method 14) to provide the title compound, mp 116-117 °C; MS (DCI/NH3) m/e 425 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 8.14 (s, IH), 7.97 (d, IH), 7.84 (s, IH), 7.83 (d, 2H), 7.76 (d, IH), 7.66 (d, 2H), 7.63 (t, IH), 7.57 (d, IH), 7.45 (d, IH). Example 133 N-[4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-1.4-benzenedicarboxamide A reaction of carboxylic acid methyl ester (50 mg), Example 142, and IM NH3 in methanol (5 mL) in a sealed tube was stirred at 60 °C for 3 days . After cooling to room temperature, the solid precipitated out from the reaction mixture was filtered, washed with ether and dried to give the desired product in 35% yield. mp 290-291 °C; MS (DCI/NH3) m e 460 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 8.15 (s, IH), 8.04 (s, 4H), 8.01 (d, 2H), 7.84 (s, IH), 7.63 (d, 2H), 7.57 (s, IH). -128- Example 134 N-[4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyll-3.5-dinitrobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp >230 °C; MS (DCI/NH3) m/e 506 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 11.17 (s, IH), 9.20 (d, 2H), 9.03 (t, IH), 8.03 (d, 2H), 7.85 (s, IH), 7.70 (d, 2H). Example 135 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazoI-l-yl1phenyll-2.4-difluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 126-128 °C; MS (DCI/NH3) m/e 453 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.79 (s, IH), 7.92 (d, 2H), 7.84 (s, IH), 7.80 (t, IH), 7.62 (d, 2H), 7.48 (t, IH), 7.26 (t, IH). Example 136 N-r4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyll-2-nitrobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 174-176 °C; MS (DCI/NH3) m/e 462 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 11.05 (s, IH), 8.20 (dd, IH), 7.93-7.75 (m, 6H), 7.63 (d, 2H). Example 137 N-r4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-3-cyanobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 162-163 °C; MS (DCI/NH3) m/e 442 (M+NH 4 )+; -129- ! H NMR (DMSO-d 6 , 300 MHz) δ 10.75 (s, IH), 8.44 (s, IH), 8.26 (d, IH), 8.11 (d, IH), 8.00 (d, 2H), 7.83 (s, IH), 7.79 (t, IH), 7.64 (d, 2H). Example 138 N-[4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyl]-1.3-benzenedicarboxamide Example 129 was processed as described in Example 133 to provide the title compound, mp 244-245 °C; MS (DCI/NH3) m/e 460 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 8.47 (s, IH), 8.1 (s, IH), 8.1 (d, 2H), 8.01 (d, 2H), 7.82 (s, IH), 7.65 (t, IH), 7.62 (d, 2H), 7.52 (s, IH). Example 139 (Z)-3-r2-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenynethenyl]benzonitrile Example (vii)-a A was processed as in Example (ix)-a (Method 14) to provide the title compound. MS (DCI/NH3) m/e 425 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 7.82 (s, IH), 7.72 (d, IH), 7.62 (s, IH), 7.54 (d, 2H), 7.51 (d, IH), 7.48 (t, IH), 7.4 (d, 2H), 6.91 (d, IH), 6.81 (d, IH). Example 140 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-nitrobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 203-204 °C; MS (DCI/NH 3 ) m e 462 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.89 (s, IH), 8.82 (t, IH), 8.48-8.41 (m, 2H), 8.02 (d, 2H), 7.88 (d, IH), 7.83 (d, IH), 7.64 (d, 2H). Example 141 3- ( aminosulfonyl)-N-r4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyllbenzamide To a solution of Example (i)-a B (112 mg, 0.380 mmol) and N-methylmorpholine (0.50 mL) in dichloromethane (3 mL) was added 3-(chlorosulfony)lbenzoyl chloride (109 mg, 0.455 mmol). The resulting solution was stirred at 23 °C for 3 hours at which point a solution -130- of saturated ammonia in methanol (2 mL) was added. The resulting white solid was filtered and washed with hexane to provide 80 mg (40%) of the desired compound, mp 177-178 °C; MS(DCI NH 3 ) 496 (M+H)+; i H NMR (DMSO-d 6 , 300 MHz) δ 8.41 (s, IH), 8.21 (d, IH), 8.06-7.99 (m, IH), 8.00 (d, 2H), 7.84 (s, IH), 7.78 (t, IH), 7.64 (d, 2H), 7.52 (br s, 2H). Example 142 methyl 4-rfr4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyllamino1carbonyllbenzoate Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 195-196 °C; MS (DCI/NH 3 ) m/e 475 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 8.12 (m, 4H), 8.0 (d, 2H), 7.84 (s, IH), 7.63 (d, 2H), 3.92 (s, 3H). Example 143 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-2-methoxybenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 100-102 °C; MS (DCI/NH 3 ) m/e 447 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.47 (s, IH), 7.95 (d, 2H), 7.82 (s, IH), 7.60 (d, 2H), 7.63 (dd, IH), 7.53 (dt, IH), 7.20 (d, IH), 7.07 (t, IH), 3.91 (s, 3H). Example 144 N-r4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyll-3-bromobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 158-160 °C; MS (DCI/NH3) m e 497 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.67 (s, IH), 8.17 (t, IH), 8.01 (d, 2H), 8.02-7.86 (m, IH), 7.82 (s, IH), 7.84-7.82 (m, IH), 7.62 (d, 2H), 7.54 (t, IH). -131- Example 145 N- [4- [3.5 -bis (trifluoromethy 1) - 1 H-pyrazol- 1 -y llphenyl 1 - 3 -methoxybenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 169-172 °C; MS (DCI/NH3) m/e 447 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.55 (s, IH), 8.02 (d, 2H), 7.82 (s, IH), 7.72 (d, IH), 7.58 (m, 3H), 7.38 (dd, IH), 7.18 (dd, IH), 3.86 (s, 3H). Example 146 N-r4-13.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-3-fluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 148-151 °C; MS (DCI/NH3) m/e 435 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.64 (s, IH), 8.0 (d, 2H), 8.05-8.0 (m, IH), 7.84 (s, IH), 7.85-7.78 (m, IH), 7.74-7.43 (m, 2H), 7.62 (d, 2H). Example 147 N- r 4-r3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyll-2-bromobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 182-184 °C; MS (DCI/NH3) m/e 495 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.55 (s, IH), 7.92 (d, 2H), 7.83 (s, IH), 7.75 (d, IH), 7.64-7.58 (m, 3H), 7.52 (td, IH), 7.46 (dd, IH). Example 148 N-[4- 3.5-bis(trifluoromethyI)-lH-pyrazol-l-yl1phenyll-1.3-benzodioxole-5- carboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 222-224 °C; MS (DCI/NH3) m/e 461 (M+NH 4 )+; -132- *H NMR (DMSO-d 6 , 300 MHz) δ 10.39 (s, IH), 7.98 (d, 2H), 7.82 (s, IH), 7.60 (m, 2H), 7.54 (d, IH), 7.09 (d, 2H), 6.18 (s, 2H). Example 149 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyl1-2.6-dichloro-3-pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 115-117 °C; MS (DCI/NH 3 ) m/e 486 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 8.25 (d, IH), 7.90 (d, 2H), 7.84 (s, IH), 7.78 (d, IH), 7.66 (d, 2H). Example 150 N- [4- [3.5-bis(trifluoromethyl)-l H-pyrazol- l-yllphenyll-2-chloro-3-pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 145-147 °C; MS (DCI/NH 3 ) m/e 452 (M+NH 4 )+; iH NMR (DMSO-d 6 , 300 MHz) δ 11.03 (s, IH), 8.57 (dd, IH), 8.16 (dd, IH), 7.91 (d, 2H), 7.82 (s, IH), 7.64 (d, 2H), 7.60 (dd, IH). Example 151 N- [4- \3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl1 -2-chloro-6-methy 1-3 - pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 155-156 °C; MS (DCI/NH3) m/e 466 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.96 (s, IH), 8.02 (d, IH), 7.90 (d, 2H), 7.83 (s, IH), 7.62 (d, 2H), 7.44 (d, IH), 2.55 (s, 3H). Example 152 N- r4- [3 ■5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyll -4-fluoro-γ-oxobenzenebutanamide -133- Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 156-158 °C; MS (DCI/NH 3 ) m e 474 (M+H)+; J H NMR (DMSO-d 6 , 300 MHz) δ 8.04 (dd, 2H), 7.91 (s, IH), 7.70 (d, 2H), 7.43 (d, 2H), 7.16 (t, 2H), 7.05 (s, IH), 3.45 (t, 2H), 2.85 (t, 2H). Example 153 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-1.2.3.4-tetrahvdro-2- naphthalenecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 199-201 °C; MS (DCI NH3) m/e 471 (M+NH 4 )+ ; IH NMR (DMSO-d 6 , 300 MHz) δ 10.35 (s, IH), 7.84 (d, 2H), 7.80 (s, IH), 7.56 (d, 2H), 7.11 (s, 4H), 2.97-2.72 (m, 7H). Example 154 (E)-l-[4-r2-(2-chlorophenyl)ethenynphenyll-3.5-bis(trifluoromethyl)-lH-pyrazole Example (vii)-a A was processed as in Example (ix)-a (Method 14) to provide the title compound, mp 81-82 °C; MS (DCI/NH3) m/e 434 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 7.92 (d, IH) 7.87 (d, 2H), 7.86 (s, IH), 7.65 (d, 2H), 7.6 (d, IH), 7.53 (d, IH), 7.44 (d, IH), 7.43 (t, IH), 7.36 (t, IH). Example 155 N- [4- 3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyll -2-(4-chlorophenoxy)-2- methylpropanamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH3) m/e 509 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.37 (s, IH), 7.92 (d, 2H), 7.80 (s, IH), 7.56 (d, 2H), 7.37 (d, 2H), 6.96 (d, 2H), 1.56 (s, 6H). -134- Example 156 N- \4- \3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyllacetamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 169-170 °C; MS (DCI/NH3) m/e 355 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.27 (s, IH), 7.78 (d, 2H), 7.79 (s, IH), 7.55 (d, 2H), 2.11 (s, 3H). Example 157 4-| " | " [4-f3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyllamino1carbonyl1benzoic acid A solution of carboxylic acid methyl ester, Example 142, and 2.5 equivalent of NaOH in ethanol was stirred at 80 °C for 3 hours Then the reaction mixture was diluted with water and acidified with IN HCl to give the precipitated product, mp 282-283 °C; MS (DCI/NH 3 ) m/e 461 (M+NH 4 )+; *H NMR (DMSO-D 6 , 300 MHz) δ 10.75 (s, IH), 8.09 (s, 4H), 8.02 (d, 2H), 7.84 (s, IH), 7.63 (d, 2H). Example 158 phenylmethyl N-r4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyllaminol-4- oxobutyllcarbamate Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH 3 ) m/e 532 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.23 (s, IH), 7.78 (d, 2H), 8.00 (d, IH), 7.52 (d, 2H), 7.34 (s, IH), 7.40-7.25 (m, 4H), 5.00 (s, 2H), 3.08 (q, 2H), 2.38 (t, 2H), 1.78 (quintet, 2H). Example 159 3-[[[4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyllaminolcarbonyllbenzoic acid A solution of Example 129 and NaOH (2.5 equivalents) in ethanol at 80° C was stirred for 3 hours, diluted with water, acidified with IM HCl, filtered and dried under vacuum to provide the title compound. -135- mp 244-245 °C; MS (DCI NH3) m/e 461 (M+NH 4 )+; l H NMR (DMSO-D 6 , 300 MHz) δ 10.78 (s, IH), 8.55 (s, IH), 8.23 (d, IH), 8.17 (d, IH), 8.02 (d, 2H), 7.84 (s, IH), 7.7 (t, IH), 7.63 (d, 2H). Example 160 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-2.6-difluorobenzamide Example (i)-c B was processed as in Example (i)-c (Method 5, 6, or 7) to provide the title compound. mp 127-128 °C; MS (DCI/NH3) m/e 453 (M+NH 4 ) + ; ! H NMR (DMSO-D 6 , 300 MHz) δ 10.38 (s, IH), 7.86 (d, IH), 7.78 (s, IH), 7.69 (t, IH), 7.59 (d, IH), 7.52 (t, IH), 7.45 (t, IH), 7.15 (t, 2H). Example 161 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-3-bromo-2-thiophenecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 139-140 °C; MS (DCI/NH3) m/e 503 (M+NH 4 ) + ; l H NMR (DMSO-d 6 , 300 MHz) δ 7.92 (d, IH), 7.90 (d, 2H), 7.83 (s, IH), 7.64 (d, 2H), 7.26 (d, IH). Example 162 N-r4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-3-methyl-2-thiophenecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 185-188 °C; MS (DCIZNH3) m/e 437 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.30 (s, IH), 7.90 (d, 2H), 7.80 (s, IH), 7.71 (d, IH), 7.58 (d, 2H), 7.06 (d, IH), 2.43 (s, 3H). Example 163 2-amino-N- [4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyllbenzamide -136- Example 163 was prepared from Example 136 using the reduction procedure described in Example 59. mp 204-206 °C; MS (DCI/NH 3 ) m/e 415 (M+H)+; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.32 (s, IH), 7.95 (d, 2H), 7.82 (s, IH), 7.67 (d, IH), 7.58 (d, 2H), 7.23 (t, IH), 6.78 (d, IH), 6.62 (t, IH), 6.37 (s, 2H). Example 164 N- 4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-2-fluoro-3-pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 110-112 °C; MS (DCI/NH 3 ) m/e 436 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.94 (s, IH), 8.42 (d, IH), 8.31 (dd, IH), 7.92 (d, 2H), 7.82 (s, IH), 7.64 (d, 2H), 7.55 (dd, IH). Example 165 N-r4-13.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-3-chloro-4-(methylsulfonyl)-2- thiophenecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 210-212 °C; MS (DCI/NH 3 ) m/e 535 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.84 (s, IH), 9.94 (s, IH), 7.82 (d, 2H), 7.75 (s, IH), 7.55 (d, 2H), 3.30 (s, 3H). Example 166 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-lH-pyrrole-2-carboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp >240 °C; MS (DCI/NH3) m/e 406 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 7.96 (d, 2H), 7.82 (s, IH), 7.58 (d, 2H), 7.13 (s, IH), 7.02 (s, IH), 6.20 (s, IH). -137- Example 167 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-3.6-dichloro-2-pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 118-119 °C; MS (DCI/NH3) m/e 486 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 11.11 (s, IH), 8.24 (d, IH), 7.92 (d, 2H), 7.82 (s, IH), 7.78 (d, IH), 7.63 (d, 2H). Example 168 N-r4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyl1-2-(2-nitrophenoxy)acetamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 170-173 °C; MS (DCI/NH3) m/e 492 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 7.78 (d, 2H), 7.22 (d, 2H), 7.05 (s, IH), 7.03 (d, IH), 6.70 (d, 2H), 6.26 (d, IH), 5.72 (s, IH), 3.92 (s, 2H). Example 169 N-14-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-4-chlorobenzeneacetamide Example (i)-c B was processed as in Example (i)-c (Method 5, 6, or 7) to provide the title compound, mp 122-124 °C; MS (DCI7NH 3 ) m/e 465 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 9.5 (s, IH), 7.9 (m, 2H), 7.6 (m, IH), 7.5 (d, IH), 7.4 (m, 3H), 7.2 (d, 2H), 3.5 (s, 2H). Example 170 N- [4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl!- 1 H-indole-2-acetamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 176-178 °C; MS (DCI/NH 3 ) m/e 470 (M+NH 4 )+; -138- *H NMR (DMSO-d 6 , 300 MHz) δ 10.92 (s, IH), 10.44 (s, IH), 7.84 (s, IH), 7.81 (d, 2H), 7.63 (d, IH), 7.53 (d, 2H), 7.36 (d, IH), 7.28 (d, IH), 7.08 (td, IH), 6.98 (td, IH), 3.78 (s, 2H). Example 171 (E)-N-[4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-3-(2-thienyl)-2-propenamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 216-218 °C; MS (DCI/NH3) m/e 449 (M+NH4)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 7.95 (d, IH), 7.90 (d, 2H), 7.82 (s, IH), 7.64 (t, IH), 7.63 (d, IH), 7.58 (d, 2H), 7.42 (d, IH), 6.68 (d, IH). Example 172 N- [4- 3.5-Bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl ~ lpy azinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 183-185 °C; MS (DCI/NH3) m/e 419 (M+NH 4 ) + ; ! H NMR (DMSO-d 6 , 300 MHz) δ 9.34 (d, IH), 8.98 (d, IH), 8.84 (dd, IH), 8.15 (d, 2H), 7.83 (s, IH), 7.64 (d, 2H). Example 173 1.1 -Dimethylethyl T \4- [4- 3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyll aminol-4- oxobutyljcarbamate Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH3) m/e 481 (M+H)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 7.80 (d, 2H), 7.95 (s, IH), 7.55 (d, 2H), 6.82 (t, IH), 2.98 (q, 2H), 2.34 (t, 2H), 1.71 (quintet, 2H), 1.38 (s, 9H). Example 174 l-Acetyl-N-r4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-4-piperidinecarboxamide -139- Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 94-95 °C; MS (DCI/NH3) m/e 466 (M+NH 4 ) + ; *H NMR (DMSO-d 6 , 300 MHz) δ 10.26 (s, IH), 7.82 (d, 2H), 7.78 (s, IH), 7.53 (d, 2H), 4.41 (d, IH), 3.87 (d, IH), 3.08 (t, IH), 2.68-2.55 (m, 2H), 2.01 (s, 3H), 1.92-1.78 (m, 2H), 1.71- 1.55 (m, 2H). Example 175 N-r4- 3.5-Bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyl1butanamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH3) m/e 383 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.26 (s, IH), 7.82 (d, 2H), 7.80 (s, IH), 7.53 (d, 2H), 2.51-2.44 (t, 2H), 1.57 (sextet, 2H), 0.91 (t, 3H). Example 176 N-[4-| " 3.5-Bis(trifluoromethyl)- IH-pyrazol- l-yl1phenyll-4-chloro-2-methoxybenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 178-180 °C; MS (DCI NH3) m/e 481 (M+NH 4 ) + ; l R NMR (DMSO-d 6 , 300 MHz) δ 10.5 (s, IH), 8.0 (d, 2H), 7.8 (s, IH), 7.7 (d, IH), 7.6 (d, 2H), 7.3 (d, IH), 7.2 (dd, IH), 3.3 (s, 3H). Example 177 N-r4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-α-methyl-4-(2- thienylcarbonyDbenzeneacetamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp <80°C; MS (DCI/NH3) m/e 555 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 8.11 (dd, IH), 7.85 (dd, 2H), 7.83 (dd, 2H), 7.79 (s, IH), 7.75 (dd, IH), 7.60 (d, 2H), 7.55 (d, 2H), 7.28 (dd, IH), 4.01 (q, IH), 1.5 (d, 3H). -140- Example 178 N-r4- .5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyn- -methyl-4-(2- thienylcarbonyPbenzeneacetamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp <100 °C; MS (DCI/NH3) m e 555 (M+NH 4 ) + ; *H NMR (DMSO-d 6 , 300 MHz) δ 10.54 (s, IH), 8.11 (dd, IH) 7.85 (dd, 2H), 7.83 (dd, 2H), 7.81 (s, IH), 7.75 (dd, IH), 7.60 (d, 2H), 7.55 (d, 2H), 7.28 (dd, IH), 4.01 (q, IH), 1.5 (d, 3H). Example 179 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyl]-2-methoxy-4-(methythio)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 164-165 °C; MS (DCI/NH3) m/e 493 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.35 (s, IH), 7.95 (d, 2H), 7.82 (s, IH), 7.65 (d, IH), 7.59 (d, 2H), 7.03 (d, IH), 6.96 (dd, IH), 3.95 (s, 3H), 2.55 (s, 3H). Example 180 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-4-hydroxy-3-nitrobenzamide Example 180A Example (i)-a B and 3-nitro-4-methoxybenzoic acid were processed as in Example (i)- a (Method 5, 6, or 7) to provide the desired compound. Example 180B N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-ynphenyll-4-hydroxy-3-nitrobenzamide A solution of example 180A (1.0 mmol) in toluene (3 mL) at -78 °C was treated dropwise with BBr3 (l.OM in toluene, 1.5 equivalents for each hydroxyl), stirred at -78 °C for 2 hours and at room temperature for 16 hours, recooled to -78 °C, treated with methanol (1 mL), warmed to room temperature, and concentrated. The residue was filtered through a MgSO4/silica gel plug with 20% acetone in hexanes and further purified by HPLC eluting with 20% acetone in hexanes. -141- mp 193-194 °C; MS (DCI/NH3) m/e 478 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.58 (s, IH), 8.58 (s, IH), 8.17 (d, IH), 7.98 (d, 2H), 7.82 (s, IH), 7.62 (d, 2H), 7.25 (d, IH). Example 181 N- r4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl ~ |phenyll-3.4-dihydroxybenzamide Example (i)-a B and 3,4-dimethoxybenzoic acid were processed as in examples (i)-a (Method 5, 6, or 7) and 180B to provide the title compound. mp 233-235 °C; MS (DCI/NH3) m/e 449 (M+NH 4 )+ ; ! H NMR (DMSO-d 6 , 300 MHz) δ 8.0 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.4 (m, 2H), 6.8 (d, IH). Example 182 N- 4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyn-2-hydroxy-6-methoxybenzamide Example (i)-a B and 2,6-dimethoxybenzoic acid were processed as in examples (i)-a (Method 5, 6, or 7) and 180B (using 1.5 equivalents of l.OM BBr3 in toluene) to provide the title compound. mp 114-116 °C; MS (DCI/NH3) m/e 446 (M+NH 4 )+ ; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.6 (s, IH), 10.3 (s, IH), 8.0 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.2 (t, IH), 6.6 (d, IH), 6.6 (d, IH), 3.8 (s, 3H). Example 183 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-2.4-bis(trifluoromethyl)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 200-201°C; MS (DO/NH 3 ) m/e 553 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 8.28 (d, IH), 8.25 (s, IH), 8.10 (d, IH), 7.88 (d, 2H), 7.84 (s, IH), 7.64 (d, 2H). Example 184 -142- N- [4- r3.5-bis(trifluoromethyl)-l H-pyrazol- l-yllphenyn-5-methyl-4-isoxazolecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 163-167 °C; MS (DCI/NH 3 ) m/e 422 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.97 (s, IH), 8.01 (d, 2H), 7.80 (s, IH), 7.61 (d, 2H), 6.69 (s, IH), 2.50 (s, 3H). Example 185 4- 3.5-Bis(trifluoromethyl)-lH-pyrazol-l-yl1-N-(2-chlorophenyl)benzamide Example (v)-a C was processed as in Example (v)-a (Method 11) to provide the title compound, mp 162-164 °C; MS (DCI/NH 3 ) m/e 451 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.4 (s, IH), 8.2 (d, 2H), 7.9 (s, IH), 7.8 (d, 2H), 7.6 (m, 2H), 7.5-7.3 (m, 2H). Example 186 4-r3.5-Bis(trifluoromethyl)-lH-pyrazol-l-yl1-N-(3-cyanophenyl)benzamide Example (v)-a C was processed as in Example (v)-a (Method 11) to provide the title compound, mp 195-196 °C; MS (DCI/NH3) m/e 442 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.8 (s, IH), 8.3 (s, IH), 8.2 (d, 2H), 8.1 (m, IH), 7.9 (s, IH), 7.8 (d, 2H), 7.6 (d, IH), 7.6 (d, IH). Example 187 4-T3.5-Bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl1-N-(2.4-difluorophenyl)benzamide Example (v)-a C was processed as in Example (v)-a (Method 11) to provide the title compound. mp 176-177 °C; MS (DCI/NH3) m/e 453 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.4 (s, IH), 8.2 (d, 2H), 7.9 (s, IH), 7.8 (d, 2H), 7.6 (m, IH), 7.4 (m, IH), 7.2 (m, IH). -143- Example 188 4-[3.5-Bis(trifluoromethyl)-lH-pyrazol-l-yll-N-(2-cvanophenyl)benzamide Example (v)-a C was processed as in Example (v)-a (Method 11) to provide the title compound. mp 203-205 °C; MS (DCI/NH 3 ) m/e 442 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.88 (s, IH), 8.22 (d, 2H), 7.93 (s, IH), 7.93 (d, IH), 7.85 (d, 2H), 7.78 (dt, IH), 7.63 (d, IH), 7.46 (dt, IH). Example 189 3.5-dimethyl-N-[4~(3.5-dimethyl- 1 H- 1.2.4-triazol- 1 -yl)phenyll-4-isoxazolecarboxamide Example (xxv)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 170-171 °C; MS (DCI/NH3) m/e 312 (M+H)+; !H NMR (CDCI3, 300 MHz) δ 7.79 (d, 2H), 7.45 (d, 2H), 7.3 (s, IH), 2.7 (s, 3H), 2.54 (s, 3H), 2.48 (s, 3H), 2.42 (s, 3H). Example 190 4-[3.5-Bis(trifluoromethyl)- IH-pyrazol- l-yll-N-(2-nitrophenyl)benzamide Example (v)-a C was processed as in Example (v)-a (Method 11) to provide the title compound, mp 173-175 °C; MS (DCI/NH3) m/e 462 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 11.0 (s, IH), 8.2 (d, 2H), 8.0 (d, IH), 7.9 (s, IH), 7.8 (d, 2H), 7.7 (m, 2H), 7.4 (m, IH). Example 191 4- [ " 3.5-Bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl1-N-(2.6-difluorophenyl)benzamide Example (v)-a C was processed as in Example (v)-a (Method 11) to provide the title compound, mp 187-188 °C; MS (DCI/NH 3 ) m/e 453 (M+NH 4 )+; -144- H NMR (DMSO-d 6 , 300 MHz) δ 10.4 (s, IH), 8.2 (d, 2H), 7.9 (s, IH), 7.8 (d, 2H), 7.4 (m, IH), 7.3 (d, IH), 7.2 (d, IH). Example 192 4-r3.5-Bis(trifluoromethyl)-lH-pyrazol-l-yn-N-(2-bromophenyl)benzamide Example (v)-a C was processed as in Example (v)-a (Method 11) to provide the title compound, mp 163-165 °C; MS (DCI/NH 3 ) m/e 496 (M+NH 4 )+; IH NMR (DMSO-d 6 , 300 MHz) δ 10.33 (s, IH), 8.2 (d, 2H), 7.89 (s, IH), 7.83 (d, 2H), 7.74 (dd, IH), 7.58 (dd, IH), 7.45 (dt, IH), 7.26 (dt, IH). Example 193 4-r3.5-Bis(trifluoromethyl)-lH-pyrazol-l-yll-N-(4-cyanophenyl)benzamide Example (v)-a C was processed as in Example (v)-a (Method 11) to provide the title compound, mp 192-193 °C; MS (DCIZNH3) m/e 442 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.87 (s, IH), 8.17 (d, 2H), 8.0 (d, 2H), 7.92 (s, IH), 7.86 (d, 2H), 7.82 (d, 2H). Example 194 4- 3.5-Bis(trifluoromethyl)-lH-pyrazol-l-yll-N-(4-pyridinyl)benzamide Example (v)-a C was processed as in Example (v)-a (Method 11) to provide the title compound. mp 234-235 °C; MS (DCI/NH3) m/e 401 (M+H)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 11.77 (s, IH), 8.78 (d, 2H), 8.34 (d, 2H), 8.25 (d, 2H), 7.94 (s, IH), 7.9 (d, 2H). Example 195 N-r4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-4-fluoro-3-(trifluoromethyl)- benzamide -145- Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 142-144 °C; MS (ESI-) m/e 485 (M-H) " ; IH NMR (DMSO-d6, 300 MHz) δ 10.7 (s, IH, ), 8.45 (m, 2H), 7.95 (d, 2H), 7.85 (s, IH), 7.75 (m, IH), 7.65 (d, 2H). Example 196 N-[2-(aminocarbonyl)phenyll-4-[3.5-bis(trifluoromethyl)- IH-pyrazol- 1-yllbenzamide Example (v)-a C was processed as in Example (v)-a (Method 11) to provide the title compound, mp 195-196 °C; MS (DCI/NH3) m/e 460 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 13.14 (s, IH), 8.7 (d, IH), 8.46 (s, IH), 8.15 (d, 2H), 7.9 (m, 5H), 7.62 (t, IH), 7.22 (t, IH). Example 197 N- 3- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-ynphenyll-4-chlorobenzeneacetamide Example (i)-b B was processed as in Example (i)-b (Method 5, 6, or 7) to provide the title compound, mp 209-211 °C; MS (DCI/NH3) m/e 465 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.6 (s, IH), 8.0 (t, IH), 7.8 (s, IH), 7.7 (d, IH), 7.6 (t, IH), 7.4-7.2 (m, 5H), 3.7 (s, 2H). Example 198 N- 3-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyl]-2.3-dichlorobenzamide Example (i)-b B was processed as in Example (i)-b (Method 5, 6, or 7) to provide the title compound. mp 119-121 °C; MS (DCI/NH3) m e 485 (M+NH 4 )+; H NMR (DMSO-d 6 , 300 MHz) δ 11.0 (s, IH), 8.1 (t, IH), 7.9 (s, IH), 7.8 (dd, 2H), 7.6 (m, 2H), 7.5 (t, IH), 7.4 (d, IH). -146- Example 199 N-f3-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-2-chloro-5-nitrobenzamide Example (i)-b B was processed as in Example (i)-b (Method 5, 6, or 7) to provide the title compound. mp 147-152 °C; MS (DCI/NH3) m/e 496 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 11.1 (s, IH), 8.6 (d, IH), 8.4 (dd, IH), 8.1 (s, IH), 7.9-7.8 (m, 3H), 7.6 (t, IH), 7.2 (d, IH). Example 200 N- [4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl1 -4-fluoro-3 -nitrobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 186-187 °C; MS (DCI/NH3) m/e 480 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.84 (s, IH), 8.78 (dd, IH), 8.42 (m, IH), 8.0 (d, 2H), 7.82 (s, IH), 7.81 (dd, IH), 7.64 (d, 2H). Example 201 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-4-fluoro-2- (trifluoromethyl)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 178-179 °C; MS (DCI/NH3) m/e 503 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.96 (s, IH), 7.91 (d, IH), 7.89 (d, 2H), 7.85 (dd, IH), 7.83 (s, IH), 7.72 (dt, IH), 7.62 (d, 2H). Example 202 N-r3-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyn-4-fluorobenzamide Example (i)-b B was processed as in Example (i)-b (Method 5, 6, or 7) to provide the title compound, mp 150-152 °C; MS (DCI/NH3) m/e 435 (M+NH 4 )+; -147- l K NMR (DMSO-d 6 , 300 MHz) δ 10.6 (s, IH), 8.2 (t, IH), 8.1 (m, 2H), 8.0 (d, IH), 7.9 (s, IH), 7.6 (t, IH), 7.5-7.3 (m, 3H). Example 203 N-[3-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl1-2.4-difluorobenzamide Example (i)-b B was processed as in Example (i)-b (Method 5, 6, or 1) to provide the title compound, mp 133-134 °C; MS (DCI/NH3) m e 453 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 7.85 (d, IH), 7.85 (d, IH), 7.78 (t, IH), 7.62 (t, IH), 7.45 (dt, IH), 7.38 (d, IH), 7.25 (dt, IH). Example 204 N-r3-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-3-cyanobenzamide Example (i)-b B was processed as in Example (i)-b (Method 5, 6, or 7) to provide the title compound, mp 160-161 °C; MS (DCI/NH3) m/e 442 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.75 (s, IH), 8.44 (s, IH), 8.27 (d, IH), 8.15 (s, IH), 8.1 (d, IH), 7.98 (d, IH), 7.88 (s, IH), 7.78 (t, IH), 7.63 (t, IH), 7.4 (d, IH). Example 205 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl]-2-bromo-3-nitrobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 213-214 °C; MS (DCI/NH3) m/e 541 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 11.6 (s, IH), 8.12 (dd, IH), 7.86 (dd, IH), 7.86 (d, 2H), 7.83 (s, IH), 7.77 (t, IH), 7.64 (d, 2H). Example 206 N- [4- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyl] -2-chloro-4-fluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. -148- mp 155-157 °C; MS (DCI/NH3) 469 (M+H)+; *H NMR (DMSO-d 6 , 300 MHz) δ 7.92 (d, 2H), 7.83 (s, IH), 7.90-7.60 (m, 2H), 7.63 (d, 2H), 7.40 (dt, IH). Example 207 N- 4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yl1phenyll-2-chloro-4- (methylsulfonyl)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 219-220 °C; MS (DCI NH3) 529 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 11.08 (br s, IH), 8.16 (d, IH), 8.05-7.95 (m, 2H), 7.96 (d, 2H), 7.84 (s, IH), 7.65 (d, 2H), 2.38 (s, 3H). Example 208 N- 4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-2.5-dichlorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 154-156 °C; MS(DCI/NH 3 ) 485 (M + NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.99 (br s, IH), 7.98 (d, 2H), 7.87 (s, 2H), 7.72-7.65 (m, 4H). Example 209 N- 4- .5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyll-2.3-difluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 147-149 °C; MS (DCI/NH3) m e 453 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.9 (s, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.7 (m, IH), 7.6 (d, 2H), 7.5 (m, IH), 7.4 (m, IH). Example 210 -149- N- 4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-3-chloro-4-fluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 138-139 °C; MS (DCI/NH3) m/e 469 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.5 (s, IH), 8.1 (dd, IH), 7.9 (m, IH), 7.8 (d, 2H), 7.7 (s, IH), 7.5 (d, 2H), 7.4 (m, IH). Example 211 N-r4-r3.5-bis(trifluoromethyl)- IH-pyrazol- l-yl1phenyll-2.5-difluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 168-169 °C; MS (DCI/NH3) m/e 453 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.8 (s, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.5-7.4 (m, 3H). Example 212 N-[4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyll-2-chloro-6-fluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 165-167 °C; MS (DCI/NH3) m/e 469 (M+NH 4 )+; *H NMR (DMSO-d , 300 MHz) δ 11.2 (s, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.7 (d, 2H), 7.6-7.4 (m, 3H). Example 213 N-[4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-2-fluoro-6- (trifluoromethyl)benzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 175-176 °C; MS (DCI/NH3) m/e 503 (M+NH 4 )+; -150- IH NMR (DMSO-d 6 , 300 MHz) δ 11.22 (s, IH), 7.86 (s, IH), 7.83 (d, 2H), 7.83-7.74 (m, 3H) 7.63 (d, 2H). Example 214 N-[4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-3-chloro-2-fluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 113-116 °C; MS(DCI/NH3) 469 (M+NH ) + ; J H NMR (DMSO-d 6 , 300 MHz) δ 10.93 (s, IH), 7.93 (d, 2H), 7.83 (s, IH), 7.80 (t, IH), 7.69 (t, IH), 7.64 (d, 2H), 7.39 (t, IH). Example 215 N-r4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-2-chloro-4-methoxybenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 140-143 °C; MS (DCI/NH3) m/e 481 (M+NH 4 )+; H NMR (DMSO-d 6 , 300 MHz) δ 10.7 (s, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.2 (d, IH), 7.0 (m, 2H), 3.8 (s, 3H). Example 216 N-r4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]-2.6-dichloro-3-nitrobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 160-161 °C; MS (DCI/NH3) m/e 530 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 8.32 (d, IH), 8.12 (d, IH), 7.78 (d, 2H), 7.68 (s, IH), 7.53 (d, 2H). Example 217 N-r4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-4-bromo-2-chlorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. -151- mp 164-167 °C; MS (DCI/NH 3 ) 531 (M+NH 4 ) + ; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.96 (s, IH), 7.93 (d, IH), 7.92 (d, 2H), 7.84 (s, IH), 7.70-7.80 (m, IH), 7.63 (d, 2H), 7.58 (d, IH). Example 218 N- 4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyll-3.4-difluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 183-185 °C; MS(DCI/NH 3 ) 453 (M+NH 4 ); ] H NMR (DMSO-d 6 , 300 MHz) δ 10.65 (s, IH), 8.30-8.24 (m, IH), 8.11-8.06 (m, IH), 7.99 (d, 2H), 7.90-7.87 (m, IH), 7.83 (s, IH), 7.80-7.60 (m, IH), 7.62 (d, 2H). Example 219 N-[4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-2-bromo-5-methoxybenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 179-181 °C; MS (DCI/NH 3 ) m/e 525 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.8 (s, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.2 (d, IH), 7.0 (d, IH), 7.0 (dd, IH), 3.8 (s, 3H). Example 220 N-r4-[3.5-bis(trifluoromethyl)-l H-pyrazol- l-yl]phenyll-4-chloro-2-hydroxybenzamide Example (i)-a B and 2-methoxy-4-chlorobenzoic acid were processed as in examples (i)-a (Method 5, 6, or 7) and 180B to provide the title compound, mp 200-202 °C; MS (DCI/NH3) m/e 467 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 8.0 (d, 2H), 7.9 (s, IH), 7.8 (s, IH), 7.6 (d, 2H), 7.0 (m, 2H). Example 221 N-[4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyl1-3-bromo-4-methoxybenzamide -152- Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 197-198 °C; MS (DCI/NH 3 ) m/e 525 (M+NH 4 ) + ; i H NMR (DMSO-d 6 , 300 MHz) δ 10.49 (s, IH), 8.26 (d, IH), 8.05 (dd, IH), 7.99 (d, 2H), 7.82 (s, IH), 7.6 (d, 2H), 7.29 (d, IH), 3.96 (s, 3H). Example 222 N- 4-[3.5-bis(trifluoromethyI)-lH-pyrazol-l-yllphenyll-3-bromo-4-hydroxybenzamide Example 221 was processed as in Example 180B to provide the title compound, mp 165-167 °C; MS (ESI-) m e 492 (M-H)-; J H NMR (DMSO-d 6 , 300 MHz) δ 10.4 (s, IH), 8.2 (d, IH), 7.97 (d, 2H), 7.87 (dd, IH), 7.81 (s, IH), 7.59 (d, 2H), 7.07 (d, IH). Example 223 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-2-chloro-4.5-difluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 149-152 °C; MS (DCI/NH 3 ) 487 (M+NH 4 ); !H NMR (DMSO-d 6 , 300 MHz) δlθ.95 (br s, IH), 8.00-7.90 (m, 2H), 7.91 (d, 2H), 7.84 (s, IH), 7.64 (d, 2H). Example 224 N-r3-13.5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2.6-difluorobenzamide Example (i)-b B was processed as in Example (i)-b (Method 5, 6, or 7) to provide the title compound, mp 142-143 °C; MS (DCI/NH3) m/e 453 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 11.2 (s, IH), 8.09 (s, IH), 7.87 (s, IH), 7.82 (d, IH), 7.63 (m, 2H), 7.42 (d, IH), 7.3 (t, 2H). Example 225 -153- N-| " 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-4-chloro-2.5-difluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 160-162 °C; MS (ESI-) m/e 468 (M-H) " ; *H NMR (CDC1 3 , 300 MHz) δ 8.52 (d, 2H), 8.0 (dd, IH), 7.85 (d, 2H), 7.15 ( s,lH), 7.40 ( dd, IH), 7.42 (d, 2H). Example 226 N-r4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-2.3.4-trifluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 122-124 °C; MS (DCI/NH3) m/e 471 (M+NH 4 )+; IH NMR (DMSO-d 6 , 300 MHz) δ 7.9 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.6-7.4 (m, 2H). Example 227 N-[4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-ynphenyl1-3.4.5-trifluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 158-159 °C; MS (DCI/NH3) m/e 471 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 8.02-7.94 (m, 4H), 7.82 (s, IH), 7.63 (d, 2H). Example 228 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-2.4.5-trifluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 109-111 °C; MS (DCI/NH3) m e 471 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.9 (s, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.8-7.6 (m, 2H). Example 229 -154- N- -[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-2.4.6-trifluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 183-185 °C; MS (DCI/NH3) 471 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) 6 11.18 (s, IH), 7.89 (d, 2H), 7.84 (s, IH), 7.65 (d, 2H), 7.46-7.40 (m, 2H). Example 230 N-[4-f3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-2.6-difluoro-3-nitrobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 187-189 °C; MS (DCI/NH 3 ) m/e 498 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 11.4 (s, IH), 8.4 (m, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.7 (d, 2H), 7.6 (m, IH). Example 231 N-r4-13.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyll-2.3.5-trifluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 169-170°C; MS (DCI/NH3) m/e 471 (M+NH 4 )+; l U NMR (DMSO-d 6 , 300 MHz) δ 10.99 (s, IH), 7.91 (d, 2H), 7.83 (s, IH), 7.88-7.78 (m, IH), 7.64 (d, 2H), 7.58-7.48 (m, IH). Example 232 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-2.4-dichloro-6-fluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 185-188 °C; MS (DCI/NH3) m/e 503 (M+NH 4 )+; l H NMR (DMSO-d 6 , 300 MHz) δ 8.01 (d, IH), 7.94-7.85 (m, 3H), 7.82 (s, IH), 7.62 (d, 2H). -155- Example 233 N-4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl-2.4-dichloro-3.5-dinitrobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (ESI-) m/e 556 (M-H)-; IH NMR (DMSO-d 6 , 300 MHz) δ 8.89 (s, IH), 7.89 (d, 2H), 7.85 (s, IH), 7.67 (d, 2H). Example 234 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-2.3.5.6-tetrafluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 235-237 °C; MS (DCI/NH 3 ) 489 (M+NH 4 ) + ; ] H NMR (DMSO-d 6 , 300 MHz) δ 8.18-8.05 (m, IH), 7.89 (d, 2H), 7.84 (s, IH), 7.67 (d, 2H). Example 235 N-r4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-ynphenyll-2.3.4.5-tetrafluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 138-140 °C; MS (DCI/NH3) 470 (M+H)+; ] H NMR (CDCI3, 300 MHz) δ 7.85 (d, 3H), 7.45 (d, 2H), 7.10 ( s.lH). Example 236 N- \4- r3 ,5-bisf trifluoromethy 1 1 H-pyrazol- 1 -y llpheny 11 -4-bromo-2.3.5.6- tetrafluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 183-184 °C; MS (DCI/NH3) m/e 507 (M+NH 4 )+; IH NMR (DMSO-d 6 , 300 MHz) δ 7.9 (s, IH), 7.9 (d, 2H), 7.7 (d, 2H). Example 237 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyn-5-methyl-2-nitrobenzamide -156- Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 188-189°C; MS (DCI/NH3) m/e 458 (M+H)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 8.12 (d, IH), 7.92-7.82 (t, 3H), 7.67-7.57 (m, 4H), 3.32 (s, 3H). Example 238 N- [3- [3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]pheny 11 -4-cy anobenzamide Example (i)-b B was processed as in Example (i)-b (Method 5, 6, or 7) to provide the title compound, mp 133-134 °C; MS (DCI/NH 3 ) m/e 442 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 0.8 (s, IH), 8.2-8.0 (m, 5H), 7.9 (d, IH), 7.8 (s, IH), 7.6 (t, IH), 7.4 (d, IH). Example 239 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-3-thiophenecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 239-240 °C; MS (DCI/NH 3 ) m/e 423 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 8.4 (m, IH), 8.0 (d, 2H), 7.8 (s, IH), 7.7-7.6 (m, 2H), 7.6 (d, 2H). Example 240 N- T4- 3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyπ-5-isoxazolecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 202-204 °C; MS (DCI/NH3) m/e 408 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 11.0 (s, IH), 8.8 (d, IH), 8.0 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.3 (d, IH). -157- Example 241 N-[4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyntetrahydro-2-furancarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 113-116 °C; MS (DCI/NH3) m/e 411 (M+H)+; *H NMR (DMSO-d 6 , 300 MHz) δ 7.93 (d, 2H), 7.80 (s, IH), 7.56 (d, 2H), 4.45 (dd, IH), 4.01 (q, IH), 3.85 (q, IH), 2.26-2.17 (m, IH), 2.07-1.98 (m, IH), 1.93-1.87 (m, 2H). Example 242 N- [4- f 3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyll -2-pyrrolidinecarboxamide Example 242 was prepared from Example 246 using the procedure described to prepare Example 125. mp 82-84 °C; MS (DCI/NH3) m e 393 (M+H)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.30 (s, IH), 7.90 (d, 2H), 7.82 (s, IH), 7.55 (d, 2H), 3.76-3.74 (dd, IH), 2.93 (t, 2H), 2.14-2.01 (m, IH), 1.88-1.75 (m, IH), 1.69 (q, 2H). Example 243 N-[4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyntetrahydro-3-furancarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 193-194 °C; MS (DCI/NH3) m/e 411 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.70 (s, IH), 8.18-8.03 (m, 3H), 7.90-7.78 (m, 2H), 4.31- 4.18 (m, IH), 4.17-3.89 (m, 4H), 2.45-2.25 (m, 2H). Example 244 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyll-1.2.3-thiadiazole-5-carboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 213-214 °C; MS (DCI/NH3) m/e 425 (M+NH 4 )+; -158- !H NMR (DMSO-d 6 , 300 MHz) δ 1 1.33 (s, IH), 9.89 (s, IH), 8.12 (d, 2H), 7.84 (s, IH), 7.66 (d, 2H). Example 245 N-[4-r3.5-bis(trifluoromethyl)- IH-pyrazol- l-yl1phenyn-2-chloro-4-pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 183-184 °C; MS (DC17NH 3 ) m/e 452 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.87 (s, IH), 8.66 (dd, IH), 8.03 (s, IH), 7.98 (d, IH), 7.80 (d, 2H), 7.82 (s, IH), 7.66 (d, 2H). Example 246 1.1 -Dimethylethyl 2-rrr4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyllamino1carbonyll- 1 -pyrrolidinecarboxylate Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 70-72 °C; MS (DCI/NH 3 ) m/e 493 (M+H)+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.36 (s, IH), 7.84-7.77 (m, 3H), 7.56 (d, 2H), 4.31-4.18 (m, IH), 3.48-3.35 (m, 2H), 1.98-1.80 (m, 4H), 1.40 (s, 3H), 1.27 (s, 6H). Example 247 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-5-nitro-2-furancarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 198-199 °C; MS (DCI/NH 3 ) m e 452 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.85 (s, IH), 7.98 (d, 2H), 7.85 (d, IH), 7.84 (s, IH), 7.7 (d, IH), 7.65 (d, 2H). Example 248 N- ( " 4- [3.5-bis(trifluorornethyl)- 1 H-pyrazol- 1 -yllphenyl]- 1 -methyl- 1 H-pyrrole-2-carboxamide -159- Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 148-149 °C; MS (DCI NH3) m/e 420 (M+NH 4 )+; l U NMR (DMSO-d 6 , 300 MHz) δ 10.0 (s, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.1 (m, 2H), 6.1 (dd, IH), 3.9 (s, 3H). Example 249 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-6-chloro-3-pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 192-194 °C; MS (DCI/NH3) m/e 452 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.79 (s, IH), 8.98 (d, IH), 8.37 (dd, IH), 7.97 (d, 2H), 7.82 (s, IH), 7.73 (d, IH), 7.64 (d, 2H). Example 250 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-4-methyl-1.2.3-thiadizole-5- carboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 164-166 °C; MS (ESI-) m/e 420 (M-H) + ; 1H NMR (DMSO-d 6 , 300 MHz) δ 11.06 (s, IH), 7.92 (d, 2H,), 7.84 (s, IH), 7.66 (d, 2H), 2.84 (s, 3H). Example 251 N- 4-| " 3.5-bis(trifluoromethyD- IH-pyrazol- l-yllphenyll-5-bromo-2-furancarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 181-182 °C; MS (DCI/NH 3 ) m/e 486 (M+NH 4 )+; !H NMR (DMSO-d 6 , 300 MHz) δ 7.96 (d, 2H), 7.82 (s, IH), 7.61 (d, 2H), 7.44 (d, IH), 6.88 (d, IH). -160- Example 252 N- 4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-ynphenyl1-3-methyl-2-furancarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp l 19-120 °C; MS (DCI/NH 3 ) m/e 421 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.4 (s, IH), 8.0 (d, 2H), 7.9 (d, IH), 7.8 (s, IH), 7.6 (d, 2H), 6.6 (d, IH), 2.4 (s, 3H). Example 253 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazoI-l-yllphenyn-5-chloro-2-thiophenecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 182-184 °C; MS (DCI/NH 3 ) m/e 457 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 8.0 (d, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 7.3 (d, IH). Example 254 N- 4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenylltetrahydro-5-oxo-2-furancarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 172-173 °C; MS (DCI/NH3) m e 425 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.58 (s, IH), 7.85 (d, 2H), 7.81 (s, IH), 7.60 (d, 2H), 5.14-5.08 (m, IH), 2.61-2.50 (m, 3H), 2.34-2.24 (m, IH). Example 255 N-r4-| " 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-5-oxo-2-pyrrolidinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp decomposes >250 °C; MS (DCI/NH 3 ) m/e 424 (M+NH 4 )+; -161- J H NMR (DMSO-d 6 , 300 MHz) δ 7.94 (s, IH), 7.86 (d, 2H), 7.81 (s, IH), 7.58 (d, 2H), 4.27 (m, IH), 2.38 (m, IH), 2.2 (m, 2H), 2.05 (m, IH). Example 256 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yIlphenyll-5-bromo-3-pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 155-157 °C; MS (DCI/NH3) m/e 489 (M+NH 4 )+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.8 (s, IH), 9.1 (d, IH), 8.9 (d, IH), 8.6 (t, IH), 8.0 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H). Example 257 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-5-nitro-3-thiophenecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 164-165 °C; MS (DCI/NH3) m/e 468 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 8.7 (d, IH), 8.6 (d, IH), 8.0 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H). Example 258 1.1 -Dimethylethyl 4-[ [4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenynaminolcarbonyll- 3-thiazolidinecarboxylate Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 82-84 °C; MS (DCI/NH3) m/e 528 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.45 (s, IH), 7.82 (s, IH), 7.80 (d, 2H), 7.58 (d, 2H), 4.68-4.42 (m, 3H), 3.58-3.43 (m, IH), 3.24-3.15 (m, IH), 1.30 (s, 9H). Example 259 N-r4-r3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyn-5-methoxy-3-thiophenecarboxamide -162- Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 213-214 °C; MS (DCI/NH3) m/e 453 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.00 (s, IH), 8.17 (d, IH), 7.93 (d, 2H), 7.82 (s, IH), 7.60 (d, 2H), 6.85 (d, IH), 3.93 (s, 3H). Example 260 N- 2- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yll-5-pyridinyll-2-chlorobenzamide Example (xxiv)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 156-159 °C; MS (DCI/NH 3 ) m/e 435 (M+H)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 11.12 (s, IH), 8.85 (d, IH), 8.48 (dd, IH), 7.95 (d, IH), 7.90 (s, IH), 7.70-7.50 (m, 4H). Example 261 N- 2- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yll-5-pyridinyll-3-cyanobenzamide Example (xxiv)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 206-208 °C; MS (DCI/NH3) m/e 426 (M+H)+; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.98 (br s, IH), 8.95 (d, IH), 8.51 (dd, IH), 8.17 (d, 2H), 8.15 (d, 2H), 7.94 (d, IH), 7.87 (s, IH). Example 262 N- 2-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yll-5-pyridinyl1-2-chloro-4.5-difluorobenzamide Example (xxiv)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 113-116 °C; MS (DCI/NH 3 ) m e 471 (M+H)+; *H NMR (DMSO-d 6 , 300 MHz) δ 11.15 (s, IH), 8.83 (d, IH), 8.45 (dd, IH), 8.02-7.91 (m, 2H), 7.94 (d, IH), 7.87 (s, IH). -163- Example 263 N-[4- 3.5-bis(trifluoromethyD- IH-pyrazol- l-yllphenyll-2.3-dibromo-5-thiophenecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 142-144 °C; MS (DCI/NH 3 ) m/e 581 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.66 (s, IH), 8.13 (s, IH), 7.95 (d, 2H), 7.85 (s, IH), 7.65 (d, 2H). Example 264 N-r4-r3.5-bis(trifluoromethyl)- IH-pyrazol- l-yllphenyll-3-fluoro-4-pyridinecarboxamide The procedure described by Shi, G.; Takagishi, S.; Schlosser, M. Tetrahetron. 1994, 50, 1129-1134 and Lecomte, L.; Ndzi, B.; Queguiner, G.; Turck, A. FR. 2,686,340-Al, hereby incorporated by reference, was used. Under reduced pressure, the volatile components were stripped off from a solution of n-butyllithium (30 mL) in hexanes. At -78 °C, potassium tert-butoxide (2.75 g, 25 mmol), THF (30 mL), and a precooled solution of 3-fluoropyridine (2.5 g 25 mmol, 2.18 mL) in THF (30 mL) were consecutively added to the residue with stirring until the alcoholate dissolved. After 4 hours at -78 °C, the reaction mixture was poured onto fresh dry ice. After evaporation to dryness, the solid salt was treated with a small excess of IM hydrogen chloride in diethyl ether. Then the mixture (desired product in hydrochloric salt form and KCl salt) was concentrated to give 2.0 g of a brown solid. This mixure was used in the coupling procedure described below in which a small amount of pyridine was used to neutralize the acidic salt form. Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound using the isofluoronicotinic acid prepared as described in the preceding paragraph, mp 152-153 °C; MS (DCI/NH3) m/e 436 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 8.80 (s, IH), 8.63 (dd, IH), 7.83 (d, 2H), 7.84 (s, IH), 7.77 (t, IH), 7.64 (d, 2H). Example 265 N-r4-B .5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yllphenyl]- 1 -methyl- 1 H-pyrazole-4- carboxamide -164- To a mixture of ethyl 4-pyrazolecarboxylate (100 mg, 0.71 mmol) and K 2 CO 3 (108 mg, 0.78 mmol) in CH 3 CN (2 mL) was added methyl iodide (67 μL, 1.07 mmol). After the reaction mixture stirred at room temperature overnight, the precipitate from the reaction was filtered and washed with ether. The filtrates were combined, washed with brine, and dried (Na 2 SO 4 ), and concentrated to provide 80 mg of desired product as an oil: MS (DCI/NH 3 ) m/e 172 (M+NH 4 )+; ] H NMR (DMSO-d 6 , 300MHz) δ 8.29 (s, IH), 7.82 (s, IH), 4.2 (q, 2H), 3.87 (s, 3H), 1.25 (t, 3H). Example (i)-a B (59 mg, 0.2 mmol), ethyl- l-methyl-4-pyrazolecarboxy late (31 mg, 0.2 mmol) and NaH (95% dry) (4.8 mg, 0.2 mmol) in DMSO (2 mL) were stirred at room temperature for 2 days and then poured into ice water with stirring. The solid was filtered, washed with water and dried to give the tittle compound in 81 % yield. mp 211-212 °C; MS (DCI/NH 3 ) m e 421 (M+NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 10.14 (s, IH), 8.37 (s, IH), 8.05 (s, IH), 7.94 (d, 2H), 7.83 (s, IH), 7.59 (d, 2H), 3.93 (s, 3H). Example 266 N- 4-[3.5-bis(trifluoromethyD- IH-pyrazol- l-yllphenyll-3.5-dimethyl-4-isoxazolecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 179-180 °C; MS (DCI/NH 3 ) m/e 436 (M+NH 4 ) + ; 1H NMR (DMSO-d 6 , 300 MHz) δ 10.40 (br s, IH), 7.88 (d, 2H), 7.83 (s, IH), 7.63 (d, 2H), 2.58 (s, 3H), 2.36 (s, 3H). Example 267 N-| " 4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyll-5-chloro-4-methoxy-3- thiophenecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 119-120 °C; MS (DCI/NH 3 ) m/e 487 (M+NH )+; -165- J H NMR (DMSO-d 6 , 300 MHz) δ 10.43 (s, IH), 8.06 (s, IH), 7.93 (d, 2H), 7.84 (s, IH), 7.6 (d, 2H), 3.93 (s, 3H). Example 268 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl1-5.6-dichloro-3-pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 175-177 °C; MS (DCI NH3) m/e 486 (M+NH 4 )+; IH NMR (DMSO-d 6 , 300 MHz) δ 9.0 (d, IH), 8.6 (d, IH), 8.0 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H). Example 269 N-[4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyll-2.6-dichloro-4-pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 215-216 °C; MS (DCI/NH3) m/e 486 (M+NH 4 )+; H NMR (DMSO-d 6 , 300 MHz) δ 10.92 (s, IH), 8.04 (s, 2H), 7.97 (d, 2H), 7.84 (s, IH), 7.67 (d, 2H). Example 270 N-[4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1phenyll-2.5-dichloro-3-pyridinecarboxamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 228-229 °C; MS (DCI NH3) m/e 487 (M+NH 4 ) + ; !H NMR (DMSO-d 6 , 300 MHz) δ 8.70 (d, IH), 8.45 (d, IH), 7.88 (d, 2H), 7.83 (s, IH), 7.64 (d, 2H). Example 271 N- r 4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yll-3-(trifluoromethyl)phenyl1-4- chlorobenzamide -166- Example (xi)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 65-67 °C; MS (ESI-) m/e 500 (M-H)-; IH NMR (DMSO-d 6 , 300 MHz) δ 10.94 (s, IH), 8.48 (d, IH), 8.29 (dd, IH), 8.04 (d, 2H), 7.92 (s, IH), 7.91 (d, IH), 7.68 (d, 2H). Example 272 N- 4- 3.5-bis(trifluoromethyl)-l H-pyrazol- l-yl]-2-fluorophenyll-2.4-difluorobenzamide Example (xvi)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 66-67 °C MS (ESI-) m/e 452 (M-H)-; *H NMR (DMSO-d 6 , 300 MHz) δ 9.96 (s, IH), 7.88 (dd, 1 H), 7.8 (s, IH), 7.68 (dd, 1 H), 7.58 (m, 2H), 7.35 (m, IH), 7.17 (m, IH); Anal, calcd for Cι 8 H 8 F 9 N 3 O: C, 47.69; H, 1.77; N, 9.27. Found: C, 47.78; H, 1.87; N, 9.18. Example 273 N- 2.4-bisr3.5-bis(trifluoromethyI)-lH-pyrazol-l-yllphenyl1-2.4-difluorobenzamide Example (xvii)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 114-115 °C MS (ESI-) m/e 636 (M-H)-; l U NMR (DMSO-d 6 , 300 MHz) δ 12.04 (s, IH), 8.21 (d, IH), 8.06 (d, IH), 7.98 (dd, 1 H), 7.88 (s, IH), 7.82 (s, IH), 7.64 (dd, 1 H), 7.38 (h, IH), 7.21 (h, IH); Anal, calcd for C 23 H 9 Fι 4 N 5 O: C, 43.34; H, 1.43; N, 10.98. Found: C, 43.7; H, 1.41; N, 10.78. Example 274 methyl 2-| " 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yll-5- (5-bromo-2-chlorobenzoyl)- aminolbenzoate Example (x)-a C was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 75-76 °C -167- MS (DCI/NH3) m/e 589 (M+NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 11.17 (s, IH), 8.52 (d, IH), 8.08 (dd, IH), 7.98 (d, IH), 7.82-7.74 (m, 3H), 7.58 (d, IH), 3.64 (s, 3H). Example 275 N-[4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yll-3-(trifluoromethyl)phenyll-3.5-dimethyl-4- isoxazolecarboxamide Example (xi)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 61-63 °C; MS (ESI-) m/e 485 (M-H)-; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.68 (s, IH), 8.38 (d, IH), 8.11 (dd, IH,), 7.93 (s, IH), 7.92 (d, IH), 2.61 (s, 3H), 2.38 (s, 3H); Anal, calcd for Cι 8 HιιF 9 N4θ 2 : C, 44.45; H, 2.28; N, 11.52. Found: C, 44.60; H, 2.37; N, 10.91. Example 276 N- r 4-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yll-3-(trifluoromethyl)phenyll-4-methyl- 1.2.3- thiadiazole-5-carboxamide Example (xi)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 134-136 °C; MS (ESI-) m/e 488 (M-H)-; ! H NMR (DMSO-d 6 , 300 MHz) δ 11.35 (s, IH), 8.18 (d, IH), 8.16 (dd, IH), 7.96 (d, IH), 7.94 (s, IH), 2.86 (s, 3H); Anal, calcd for Ci6H 8 F 9 N 5 OS: C, 39.27; H, 1.68; N, 14.18. Found: C, 39.29; H, 1.71; N, 13.81. Example 277 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yn-3-chlorophenyll-3.5-dimethyl-4- isoxazolecarboxamide Example (xiii)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 64-65 °C; -168- MS (ESI-) m/e 451 (M-H)- ; IH NMR (DMSO-d 6 , 300 MHz) δ 10.54 (s, IH), 8.12 (d, IH), 7.91 (s, IH), 7.84 (d, IH), 7.77 (dd, IH), 2.48 (s, 3H), 2.36 (s, 3H); Anal, calcd for Cι 7 HnClF 6 N 4 O 2 : C, 45.09; H, 2.44; N, 12.37. Found: C, 45.26; H, 2.5; N, 11.98. Example 278 N-[4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yn-2-(trifluoromethyl)phenyll-3.5-dimethyl-4- isoxazolecarboxamide Example (xii)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 145-146 °C; MS (ESI-) m/e 485 (M-H)-; ! H NMR (DMSO-d 6 , 300 MHz) δ 8.17 (d, IH), 8.06 (dd, IH), 7.92 (d, 2H). 7.9 (s, IH), 2.62 (s, 3H), 2.37 (s, 3H); Anal, calcd for Cι 8 HnF 9 N 4 O 2 : C, 44.45; H, 2.28; N, 11.52. Found: C, 44.39; H, 2.16; N, 11.3. Example 279 N-r4-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-2-methylphenyll-4-methyl-1.2.3-thiadiazole- 5-carboxamide Example (xiv)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 196-197 °C; MS (ESI-) m e 434 (M-H)- ; *H NMR (CDC1 3 , 300 MHz) δ 8.04 (s, IH), 7.73 (d, IH), 7.54 (d, 2H), 7.47 (dd, IH), 2.88 (s, 3H), 2.33 (s, 3H); Anal, calcd for Cι 6 HιιF6N 5 OS: C, 44.14; H, 2.54; N, 16.08. Found: C, 44.25; H, 2.45; N, 15.97. Example 280 N-r4-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yll-2-methoxyphenyl1-4-methyl-1.2.3- thiadiazole-5-carboxamide -169- Example (xv)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 119-121 °C; MS (ESI-) m/e 450 (M-H)-; ] H NMR (DMSO-d 6 , 300 MHz) δ 8.14 (d, IH); 7.94 (s, IH), 7.75 (d, IH), 7.23 (dd, IH), 3.97 (s, 3H), 2.85 (s, 3H); Anal, calcd for Cι 6 Hι ιF6N 5 O 2 S: C, 42.57; H, 2.45; N, 15.51. Found: C, 43.19; H, 2.46; N, 14.46. Example 281 4-chloro-N- 4-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yllphenynbenzamide Example (xix)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 145-146 °C; MS (DCI/NH3) m/e 370 (M+H)+; ! H NMR (CDCI3, 300 MHz) δ 7.85 (d, 2H), 7.78 (d, 2H), 7.49 (d, 2H), 7.47 (d, 2H), 6.67 (s, IH), 2.36 (s, 3H). Example 282 4-methyl-N-r4-r5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yllphenyll-1.2.3-thiadiazoIe-5- carboxamide Example (xix)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 51-53 °C; MS (DCI/NH3) m/e 368 (M+H)+; !H NMR (CDCI3, 300 MHz) δ 7.85 (d, 2H), 7.78 (d, 2H), 7.49 (d, 2H), 7.47 (d, 2H), 6.67 (s, IH), 2.36 (s, 3H). Example 283 3.5-Dimethyl-N-r4-r5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yllphenyll-4- isoxazolecarboxamide Example (xix)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 180-181 °C; -170- MS (DCI/NH3) m/e 365 (M+H)+; *H NMR (CDCI3, 300 MHz) δ 7.85 (d, 2H), 7.78 (d, 2H), 7.49 (d, 2H), 7.47 (d, 2H), 6.67 (s, IH), 2.36 (s, 3H). Example 284 4-Chloro-N- 4-(5-methyl-lH-pyrazol-l-yl)phenyllbenzamide Example (xxi)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 189-191 °C; MS (DCI/NH3) m/e 312 (M+H)+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.50 (s, IH), 8.02 (d, 2H), 7.91 (d, 2H), 7.63 (d, 2H), 7.54 (d, IH), 7.50 (d, 2H), 6.26 (d, IH), 2.34 (s, 3H). Example 285 4-Methyl-N-r4-(5-methyl-lH-pyrazol-l-yl)phenyll-1.2.3-thiadiazole-5-carboxamide Example (xxi)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 163-164 °C; MS (DCI/NH3) m/e 300 (M+H)+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.89 (s, IH), 7.83 (d, 2H), 7.55 (d, IH), 7.53 (d, 2H), 6.27 (d, IH), 2.93 (s, 3H), 2.35 (s, 3H). Example 286 3.5-dimethyl-N-[4-(5-methyl- IH-pyrazol- l-yl)phenyll-4-isoxazolecarboxamide Example (xxi)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 151-152 °C; MS (DCI/NH 3 ) m/e 297 (M+H)+; !H NMR (DMSO-d 6 , 300 MHz) δ 10.23 (s, IH), 7.79 (d, 2H), 7.54 (d, IH), 7.50 (d, 2H), 6.26 (dd, IH), 2.57 (s, 3H), 2.36 (s, 3H), 2.32 (s, 3H). Example 287 3.5-dimethyl-N-[4- 3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl1-4-isoxazolecarboxamide -171- Example (xxii)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 177-178 °C; MS (DCI/NH3) m/e 351 (M+H)+; ] H NMR (DMSO-d 6 , 300 MHz) δ 10.24 (s, IH), 8.69 (d, IH), 7.86 (dd, 4H), 7.04 (d, IH), 2.57 (s, 3H), 2.36 (s, 3H). Example 288 N-[4-[ " 5-hydroxy-3-(trifluoromethyl)- IH-pyrazol- l-yl]phenyll-4-methyl-l.2.3-thiadiazole-5- carboxamide Example (xxiii)-a C was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 177- 179 °C; MS (ESI-) m/e 368 (M-H)-; IH NMR (DMSO-d 6 , 300 MHz) δ 10.87 (s, IH), 8.82 (d, 2H), 8.67 (d, 2H), 5.82 (s, IH), 2.84 (s, 3H). Example 289 N-[4-(3.5-dimethyl-lH-1.2.4-triazol-l-yl)phenyll-4-methyl-1.2.3-thiadiazole-5-carboxamide Example (xxv)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 144-145 °C; MS (DCI/NH3) m/e 315 (M+H)+; *H NMR (CDCI3, 300 MHz) δ 7.74 (d, 2H), 7.28 (d, 2H), 3.01 (s, 3H), 2.51 (s, 3H), 2.42 (s, 3H). Example 290 3-amino-N-(4-(3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)isonicotinamide Example 290A 3-nitro-nicotinic acid 3-Nitro-4-methylpyridine (2 g, 14 mmol) in water (200 mL) was refluxed while a saturated solution of potassium permanganate (4.43 g, 28 mmol) in water (20 mL) was added dropwise over a 4 hour period. At the end of addition, the solution was refluxed for another -172- two hours. The solution was filtered while hot, the brown manganese dioxide filter cake was extracted twice with hot water, and the filtrates were combined and concentrated in vacuo. Then the solid was redissolved with a minimum amount of water, and concentrated hydrochloric acid was added to acidify the solution to pH = 3. The acidic solution was concentrated in vacuo to give 800 mg of brown product (carboxylic acid salt and KCl salt). The product mixture was carried for next step without further purification. Reference: Kataoka, M.; Morisawa, Y.; Kitano, N. J. Med. Chem. 1976, 30(4), 483-487. Example 290B 3-nitro-N-(4-(3.5-bis(trifluoromethyl)- IH-pyrazol- l-yl)phenyl)isonicotinamide Example (i)-a B and Example 290A were processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 207-209 °C; MS (DCI) m/e (M+H)+; l R NMR (DMSO-d6, 300 MHz) δ 11.16 (s, IH), 9.40 (s, IH), 9.10 (d, IH, J = 6Hz), 7.94 (d, IH, J=6 Hz), 7.85 (d, 2H, J=9 Hz), 7.84 (s, IH), 7.65 (d, 2H, J=9 Hz). Example 290 3-amino-N-(4-(3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)isonicotinamide To a slurry 5% Pd-C (11 mg) in ethyl acetate (10 mL) was added Example 290B (110 mg, 0.247 mmol). The resulting mixture was hydrogenated at 4 atm pressure at room temperature for 18 hours. After purging the reaction with nitrogen and filtering the mixture through a plug of diatomaceous earth, the solution was concentrated in vacuo and purified with 10 g of silica-gel using ethyl acetate: hexanes (v/v; 3:7) to afford the title compound as a white powder (80 mg, 77% yield), mp 101-102 °C; MS (DCI/NH 3 ) m/e 416 (M+H)+; *H NMR (DMSO-d6, 300 MHz) δ 10.55 (s, IH), 8.87 (s, IH), 7.94 (d, 2H), 7.86-7.82 (m, 2H), 7.61 (d, 2H), 7.54 (d, IH), 6.40 (s, 2H). Example 291 N-(4-(3.5-bis(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-3-chloro-5-methoxyisonicotinamide -173- Example (i)-a B was processed as described in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 187-188 °C; MS (DCI/NH3) m/e 482 (M+NHJ + ; l NMR (DMSO-d6, 300 MHz) δ 10.81 (s, IH), 7.98 (d, 2H), 7.85 (s, IH), 7.65 (d, 2H), 7.58 (s, IH), 7.35 (s, IH), 3.95 (s, 3H). Example 292 N-(6-(3.5-bis(trifluoromethyD- IH-pyrazol- l-yl)-3-pyridinyl)-2-fluorobenzamide Example 292A 5-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yll-2-nitropyridine To a cold slurry (0°C) of sodium hydride (95%, 160 mg, 6.67 mmol) in dimethylformamide (10 mL) was added 3,5-bis(trifluoromethyl)pyrazole (1.12g, 5.50 mmol). The resulting suspension was stirred for 30 minutes. A solution of 2-chloro-4-nitropyridine (867 mg, 5.5 mmol) was added. The resulting mixture was heated at reflux for 12 hours, then cooled to room temperature. The mixture was poured into saturated sodium chloride solution (100 mL). The aqueous mixture was extracted with ethyl acetate (3 x 100 mL) and the combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography using 20% ethyl acetate/hexane to afford a yellow oil (1.78 g, 99% yield). MS (DCI/NΗ3) m/e 326 (M + H)+; !H NMR (DMSO-d6, 300 MHz) δ 9.39 (d, IH), 8.86 (dd, IH), 8.21 (d, IH), 8.02 (s, IH). Example 292B 5-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yll-2-pyridinylamine To a a slurry of 10% palladium on carbon (192 mg) in ethyl acetate (90 mL) under a nitrogen atmosphere was added a solution of Example 292A (1.77 g, 5.43 mmol) in ethyl acetate (10 mL). A hydrogen balloon was placed on the reaction flask and the reaction mixture was maintained under a hydrogen atmosphere for 20 hours. The reaction flask was purged with nitrogen and then the catalyst was filtered off through a diatomaceous earth/silica gel plug to afford an oil (1.20g, 75% yield). MS (DCI/NΗ3) m/e 297 (M + H)+; -174- !H NMR (DMSO-d6, 300 MHz) δ 7.82 (d, IH), 7.72 (s, IH), 7.43 (d, IH), 7.15 (dd, IH), 5.90 (s, 2H). Example 292 N-(6-(3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl)-3-pyridinyl)-2-fluorobenzamide Example 292B was processed as described in Method 5, 6, or 7 to provide the title compound, mp 164-165 °C; MS (DCI/NH3) m/e 419 (M + H)+; iH NMR (DMSO-d6, 300 MHz) δ 10.96 (s, IH), 8.88 (d, IH), 8.45 (dd, IH), 7.92 (d, IH), 7.87(s, IH), 7.77 (m, IH), 7.66 (m, IH), 7.40 (m, 2H). Example 293 methyl 2-(3.5-bis(trifluoromethyl)-l H-pyrazol- l-yl)-5-((2-fluorobenzoyl)amino)benzoate Example 293 A methyl 2-[3.5-bis(trifluoromethyl)- IH-pyrazol- l-yl]-5-nitrobenzoate 3,5-Bis(trifluoromethyl)pyrazole (1.02 g, 5 mmol) in DMF (5 mL) was added to a mixture of NaΗ (23 mg, 5 mmol, 95%) in DMF (20 mL). The mixture turned brown in 5 minutes and was stirred at room temperature for one hour. Then methyl 2-fluoro-5- nitrobenzoate (1.0 g, 5.0 mmol) 1 in DMF (10 mL) was added to the solution drop wise via syringe. Upon finishing the addition, the solution was heated to 45 °C for 10 hours. Then it was cooled to room temperature, diluted with water (20 mL) and extracted with ethyl acetate (3 X 20 mL). The combined organic portions were washed with IN ΗC1 (2 X 20 mL), dried over Na2SO4, filtered and concentrated in vacuo. This crude product was chromatographed over silica gel, using ethyl acetate: hexanes (2:8 to 3:7) in sequence. The fractions were collected and concentrated in vacuo to give the title compound (1.5 g, 79% yield) as a brown oil. Deutsch, J.; Niclas, Η. J. Synth.Commun.1991, 21(4), 505-513. MS (DCI NΗ 3 ) m/e 371 (M+NH4)+; Η NMR (DMSO-d6, 300 MHz) δ 8.76-8.64 (m, 2H) 8.17 (d, IH, J = 6 Hz), 7.94 (s, IH). Example 293B methyl 5-amino-2-[3.5-bis(trifluoromethyl)- IH-pyrazol- 1-yllbenzoate -175- The nitro group of Example 293A was reduced with iron powder and ammonium chloride as described in Example 355B.. mp 45-47°C; MS (DCI/NH 3 ) m/e 371 (M+NH4)+; 2 H NMR (DMSO-d6, 300 MHz) δ 7.6 (s, H), 7.20 (d, IH, J=6 Hz), 6.76 (dd, IH, J=9,3 Hz), 5.92 (s, 2H), 3.46 (s, 3H). Example 293 methyl 2-(3.5-bis(trifluoromethyl)-l H-pyrazol- l-yl)-5-((2-fluorobenzoyl)amino)benzoate Example 293 B was processed as in Method 5 or 6, or 7 to provide the title compound. MS (DCI/NH3) m e 493 (M+NH 4 ) + ; !H NMR (DMSO-d6, 300 MHz) δ 8.54 (d, IH), 8.16 (dd, IH), 7.80 (d, IH), 7.76 (td, IH), 7.69-7.60 (m, IH), 7.45-7.35 (m, 2H), 3.65 (s, 3H). Example 294 4-(aminomethyl)-N-(4-(3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2-chlorobenzamide Example 294 A 4-cyano-2-chlorobenzoic acid Under a nitrogen atmosphere, Zn(CN) 2 (58 mg, 0.50 mmol) and 4-bromo-2- chlorobenzoic acid (200 mg, 0.90 mmol) were added to dry dimethylformamide (5 mL), followed by tetrakis(triphenylphosphine)palladium(0) (43 mg, 0.036 mmol). The resulting yellow slurry was heated to 80 °C overnight. After it was cooled to room temperature, it was diluted with ethyl ether (20 mL), and washed with water (2 X 10 mL). Then the ethereal portion was collected, dried with Na 2 SO 4 , filtered and concentrated in vacuo to give 2-chloro- 4-cyanobenzoic acid (60 mg, 37% yield) as a white solid. Reference: Magidson, O.J.; Trawin, A.I. Chem Ber. 1936, 69, 537-544. Example 294B N- { 4- \3.5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl } -2-chloro-4-cyanobenzamide Example (i)-a B and Example 294A were processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NΗ3) m/e 476 (M+NH 4 ) + -176- 1H NMR (DMSO-d6, 300 MHz) δ 8.03 (s, IH), 8.0 (d, IH), 7.9 (m, 3H), 7.8 (s, IH), 7.6 (d, 2H). Example 294 4-(aminomethyl)-N-(4-(3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-2-chlorobenzamide To a solution of Example 294B (40 mg, 0.087 mmol) in methanol (10 mL) was added colboltous chloride hexahydrate (23 mg, 0.17 mmol) and sodium borohydride (34 mg, 0.9 mmol) in portions at 0 °C with stirring. After 4 hours at 0 °C, the black slurry was acidified with IN hydrochloric acid solution until the solid was totally dissolved. After removal of methanol in vacuo, the aqueous layer was made alkaline with NaOH solution and extracted with ethyl acetate (3 X 20 mL). The combine organic layers were washed with saturated sodium chloride solution (2 X 20 mL) and dried over Na2SO4, filtered and concentrated in vacuo to give the title compound (30 mg,75% yield) as a pale yellow powder. Reference: Suzuki, Y.; Miyaji, Y.; Imai, Z. Tetrahedron Lett, 1969, 4555-4558. mp 90-93°C; MS (DCI/NH3) m/e 480 (M+NH 4 ) + ; *H NMR (DMSO-d6, 300 MHz) δ 7.94 (d, 2H), 7.84 (s, IH), 7.66-7.55 (m, 4H), 7.42 (d, IH), 4.39 (s, 2H), 3.90 (s, 2H). Example 295 N-(4-(3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2-methylacrylamide Example (i)-a B and was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 160-162 °C; MS (DC17NH3) m/e 364 (M+H)+; 1H NMR (DMSO-d6, 300 MHz) δ 10.1 (s, IH), 7.9 (d, 2H), 7.8 (s, IH), 7.6 (d, 2H), 5.8 (d, IH), 5.6 (d, IH), 2.5 (s, 3H). Example 296 N-(4-(3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-4-chloro-2-fluorobenzamide Example (i)-a B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 156-158 °C; MS (ESI) m/e 486 (M+Cl) " ; 450 (M-l) " ; -177- 'HNMR (300 MHz, CDCL) δ 8.53 (d, IH, J=16.2 Hz), 8.16 (dd, IH, J=8.7, 8.4Hz), 7.84 (m, 2H), 7.52 (m, 2H), 7.35 (dd, IH, J=8.4, 1.8 Hz), 7.27 (dd, IH, J=12.0, 1.8 Hz), 7.08 (s, IH). Anal. Calcd for C 18 H 9 ClF 7 N 3 O: C, 47.86; H, 2.01; N, 9.30. Found: C, 48.14; H, 2.05; N, 9.11. Example 297 N-(5-(3.5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl)-2-pyridinyl)-2-fluorobenzamide Example 297A 5-chloro-2-nitropyridine To cold (0 °C) concentrated sulfuric acid (80 mL) was added 30% hydrogen peroxide (40 mL). To this solution was added 2-amino-5-chloropyridine (4.00 g, 31.11 mmol). The solution became lime colored within 30 minutes. The reaction mixture was allowed to warm to room temperature and stirred for 20 hours. The reaction mixture was then poured into ice water and a white precipitate formed. This solid was filtered and dried in vacuo to afford 5- chloro-2-nitropyridine (3.10 g, 63% yield). MS (DCI/NH3) m/e 129 (M+H for aniline)+; !H NMR (DMSO-d6, 300 MHz) δ 8.78 (m, IH), 8.37 (m, 2H). Example 297B 5-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl1-2-nitropyridine To a cold slurry (0 °C) of sodium hydride (95%, 439 mg, 18.30 mmol) in dimethylformamide 3.0 mL) was added 3,5-bis(trifluoromethyl)pyrazole (2.50 g, 12.30 mmol). The resulting suspension was stirred for 30 minutes. A solution of 5-chloro-2- nitropyridine (1.90 g, 12.00 mmol) was added. The resulting mixture was heated at reflux for 24 hours, then cooled to room temperature. The mixture was poured into saturated sodium chloride solution (100 mL). The aqueous mixture was extracted with ethyl acetate (3 x 100 mL) and the combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography using 20% ethyl acetate/hexane to afford a yellow oil (1.17 g, 30% yield). MS (DCI/NH3) m/e 297 (M+l for aniline)+; J H NMR (DMSO-d 6 , 300 MHz) δ 9.38 (d, IH), 8.88 (dd, IH), 8.21 (d, IH), 8.02 (s, IH). Example 297C -178- 5-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yll-2-pyridinamine To a solution of Example 297B (183 mg, 0.54 mmol) in acetic acid (3.0 mL) was added zinc powder (71 mg, 1.10 mmol). The resulting mixture was heated at 70 °C for one hour. The reaction mixture was cooled and poured into saturated sodium bicarbonate solution (100 mL). The aqueous layer was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were dried over sodium sulfate filtered and concentrated to a crude oil which was used in the next step without further purification. MS (DCI/NΗ3) m/e 297 (M + H)+; ] H NMR (DMSO-d 6 , 300 MHz) δ 7.81 (d, IH), 7.74 (s, IH), 7.44 (d, IH), 7.15 (dd, IH), 5.93 (s, 2H). Example 297 N-(5-(3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl)-2-pyridinyl)-2-fluorobenzamide Example 297C was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 153-155 °C; MS (DCI/NH3) m/e 419 (M + H)+; !H NMR (DMSO-d6, 300 MHz) δ 10.95 (s, IH), 8.88 (d, IH), 8.47 (dd, IH), 7.92 (d, IH), 7.87(s, IH), 7.77 (m, IH), 7.66 (m, IH), 7.40 (m, 2H). Example 298 N- { 3-amino-4-r3.5-bis(trifluoromethyl)- IH-pyrazol- 1 -yllphenyl 1 -2-fluorobenzamide Example 298A 2-[3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-5-nitrobenzoic acid To a cold (0 °C) slurry of potassium hydride (35%, 1.09g, 9.55 mmol) in tetrahydrofuran (20.0 mL) was added 3,5-bis(trifluoromethyl)pyrazole (1.56 g, 7.64 mmol) in portions over 15 min. The resulting mixture was stirred at 0 °C for 30 min., then solid 2- fluoro-4-nitrobenzoic acid (708 mg, 3.82 mmol) was added. The mixture was heated at reflux for 20 hours, cooled, then poured into IN ΗC1 solution (100 mL). The aqueous layer was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The crude oil was used in the next step without purification (450 mg, 34%). MS (DCI/ΝΗ3) m/e 357 (M+NH 4 )+ (for corresponding aniline); -179- *H NMR (DMSO-d6, 300 MHz) δ 8.72 (d, IH), 8.60 (dd, IH), 8.09 (dd, IH), 7.88 (s, IH). Example 298B 2-(trimethylsilyl)ethyl 2- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yll-5-nitrophenylcarbamate A mixture of Example 298A (421 mg, 1.23 mmol), triethylamine (1.0 mL, 6.15 mmol), diphenylphosphorylazide (0.40 mL, 1.85 mmol) and β-trimethylsilylethanol (0.88 mL, 6.15 mmol) in toluene was heated at 70 °C for 20 hours. The reaction mixture was cooled and concentrated in vacuo. Purification of the crude residue with flash chromatography eluting with 10% ethyl acetate/hexane affored the title compound (230 mg, 39% yield) as a yellow oil. MS (DCI/NΗ3) m/e 502 (M + NH 4 )+; iH NMR (DMSO-d6, 300 MHz) δ 9.82 (s, IH), 8.81 (d, IH), 8.03 (dd, IH), 7.85 (s, IH), 7.75 (d, IH), 4.09 (t, 2H), 0.95 (t, 2H), 0.02 (s, 9H). Example 298C 2-(trimethylsilyl)ethyl 5-amino-2-13.5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenylcarbamate Example 298B was reduced using general hydrogenation method described in method 4. !Η NMR (DMSO-d6, 300 MHz) δ 8.71 (s, IH), 7.60 (s, IH), 6.99 (dd, IH), 6.38 (dd, IH), 5.68 (s, 2H), 4.03 (t, 2H), 0.91 (t, 2H), 0.02 (s, 9H). Example 298D 2-(trimethylsilyl)ethyl 2-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yll-5-r(2- fluorobenzoyl)amino]phenylcarbamate Example 298C was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NΗ3) m/e 594 (M + NH 4 )+; *H NMR (DMSO-d6, 300 MHz) δ 10.78 (s, IH), 9.24 (s, IH), 8.25 (d, IH), 7.74 (s, IH), 7.65 (m, 3H), 7.38 (m, 3H), 4.05 (t, 2H), 0.95 (t, 2H), 0.02 (s, 9H). Example 298 Λ^-f 3-amino-4- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllphenyl}-2-fluorobenzamide -180- A mixture of Example 298D (49 mg, 0.085 mmol) and tetrabutylammonium fluoride (01.5 mL, 015 mmol) in tetrahydrofuran (l.OmL) and DMSO (1.0 mL) was heated at 80 °C for 48 hours. The reaction mixture was cooled and purified directly by flash chromatography using 40%ethyl acetate/hexane affording the title compound as an oil (37 mg, 99% yield). MS (DCI/NH3) m/e 450 (M + NH 4 )+; *H NMR (DMSO-d6, 300 MHz) δ 7.71 (s, IH), 7.70-7.75 (m, 3H), 7.40-7.30 (m, 2H), 7.15 (d, IH), 6.85 (dd, IH), 5.38 (s, 2H). Example 299 N-(4-(3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl)-3-cyanophenyl)-2-fluorobenzamide Example 299A 5-amino-2- 3.5-bis(trifluoromethyl)-lH-pyrazol-l-yllbenzonitrile Sodium hydride (95%, 130 mg, 5.39 mmol) was combined with dimethylformamide (20 mL) under a nitrogen atmosphere. To this slurry was added a solution of 3,5- bis(trifluoromethyl)pyrazole (1 g, 4.9 mmol) in dimethylformamide (5 mL). The mixture turned brown in 5 minutes and was stirred at room temperature for one hour. Then 2-fluoro- 5-nitro-benzonitrile (814 mg, 4.9mmol) in dimethylformamide (10 mL) was added to the solution drop wise by syringe. Upon finishing addition, the solution was heated to 45 °C for 10 hours. Then it was cooled to room temperature, diluted with Η2O (20 mL) and extracted with ethyl acetate (3 X 20 mL). The combined organic portions were washed with IN HCl (2 X 20 mL), dried over Na2SO4, filtered and concentrated in vacuo. This crude product, obtained as a brown oil (1.4 g, 84% yield), was used without additional purification. Example 299B 2-r3.5-bis(trifluoromethyl)-lH-pyrazol-l-yn-5-nitrobenzonitrile The nitro group of Example 299A was reduced with iron powder and ammonium chloride as described in Example 355B. mp 124-126°C; MS (DCI/NΗ3) m/e 338 (M+NH 4 ) + ; iH NMR (DMSO-d6, 300 MHz) δ 9.31 (s, IH), 7.71 (d, IH), 7.05 (d, IH), 6.94 (dd, IH). Example 299 N-(4-(3.5-bis(trifluoromethyl)-lH-pyrazol-l-yl)-3-cyanophenyl)-2-fluorobenzamide -181- Example 299B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 132-134°C; MS (DCI/NH3) m/e 460 (M+NH 4 ) + ; iH NMR (DMSO-d6, 300 MHz) δ 11.15 (s, IH), 8.58 (d, IH), 8.47 (d, IH), 8.20 (dd, IH), 8.04 (s, IH), 7.47-8.28 (m, 4H). Example 300 N- { 4-f 5-cyano-3-(trifluoromethyl)- IH-pyrazol- 1 -yllphenyl } -2-fluorobenzamide Example 300A 2.2.2-trifluoroacetaldehyde N-(4-nitrophenyl)hydrazone A IL round bottom flask equipped with a stir bar and a 250 mL pressure equalizing dropping funnel was charged with trifluoroacetic acid (10.0 mL, 130 mmol) and ether (350 mL). To this cold solution (0 °C) solution was added lithium aluminum hydride (1 M soln. in ether, 100 mL, 100 mmol) via the dropping funnel over 20 min. The resulting solution was stirred at 0 °C for 1 h. The reaction was quenched by the addition of methanol (10 mL), followed by water (10 mL), then concentrated ΗC1 (17 mL). The ether layer was extracted with water (300 mL), then dried over sodium sulfate, filtered and concentrated. The crude material was used in the next step without further purification. A mixture of the trifluoroacetaldehyde thus produced (ca. 130 mmol), 4-nitrophenylhydrazine (15.02 g, 98.04 mmol), ethanol (250 mL) and concentrated ΗC1 (5.0 mL) were heated to 100 °C for 2 hours. The reaction was cooled, approximately 90% of the ethanol was removed in vacuo, and then ether (350 mL) was added. The ether layer was washed with saturated sodium bicarbonate solution (300 mL), then dried over sodium sulfate, filtered and concentrated to a crude orange solid (22.8 g, 99%) which was pure enough to use in the next step. MS (DCI/ΝΗ3) m/e 251 (M + NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 11.78 (s, IH), 8.20 (d, 2H), 7.55 (q, IH), 7.19 (d, 2H). Example 300B 2.2.2-trifluoro-N-(4-nitrophenyl)ethanehydrazonoyl chloride To a solution of Example 300A (7.4 g, 0.031 mol) in DMF (30 mL) was added a solution of Ν-chlorosuccinimide (4.38 g, 0.033 mol, 1.05 eq) in DMF (15 mL) dropwise at 0 °C. After addition, the resulting dark green mixture was stirred at room temperature for two -182- hours. The reaction mixture was then poured into an ice water bath with stirring. A light brown solid formed after about 30 minutes at which point the solid was filtered, and dried in a vacuum oven at 40 "C for 12 hours to give 11 g of an orange solid which was pure enough to use in the next step. MS (DCI/NH3) m/e 285 (M+NH 4 ) + ; iH NMR (DMSO-d6, 300 MHz) 6 11.30 (s, IH), 8.24 (d, 2H), 7.44 (d, 2H). Example 300C l-(4-nitrophenyl)-3-(trifluoromethyl)-lH-pyrazole-5-carbonitrile To a 250 mL round bottom flask charged with Example 300B (8.8 lg, 33.75 mmol) at room temperature was added toluene (68 mL) followed by 2-chloroacrylonitrile (5.4 mL, 67.5 mmol), then triethylamine (10.35 mL, 74.25 mmol). The resulting dark reaction mixture was heated to 80 °C for 1 hour. The reaction mixture was cooled and diluted with ethyl acetate (200 mL). The organic layer was washed with 1 N hydrochloric acid solution (150 mL), dried over sodium sulfate, filtered and concentrated. The crude residue was purified by flash chromatography using 10% ethyl acetate/90% hexane affording the title compound as a yellow oil (4.94 g, 58% yield). MS (DCI/NΗ3) m/e 270 (M + NH 4 ) + (For the corresponding aniline produced in the analysis.) !H NMR (DMSO-d6, 300 MHz) δ 8.53 (d, 2H), 8.20 (s, IH), 8.13 (d, 2H). Example 300D l-(4-aminophenyl)-3-(trifluoromethyl)-lH-pyrazole-5-carbonitrile To a 50 mL round bottom flask was Example 300C (1 g, 3.5 mmol), ammonium chloride (138 mg, 2.8 mmol, 0.8 eq), iron powder(1.59 g, 28 mmol, 8 eq) and a mixture of ethanol: Η 2 O (3: 1, 32 mL). The mixture was heated to reflux for 2 hours. After it was cooled to room temperature, the mixture was passed through a diatomaceous earth pad and the filtrate was concentrated in vacuo. The resulting solid was redissolved in dichloromethane (30 mL) and washed with NaHCO 3 solution (30 mL). The dichloromethane portion was dried with Na j SO 4 and concentrated in vacuo to give the amine (800 mg, 91%) as a crude brown solid which was pure enough to use in the next step. MS (DCI/NH3) m/e 252 (M+NH 4 ) + ; iH NMR (DMSO-d6, 300 MHz) δ 7.96 (s, IH), 7.38 (d, 2H), 6.70 (d, 2H), 5.71 (s, 2H). Example 300 -183- N-{4- 5-cyano-3-(trifluoromethyl)-lH-pyrazol-l-yllphenyl)-3-fluoroisonicotinamide Example 300D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 161-162 °C; MS (DCI/NΗ3) m/e 393 (M+NH 4 ) + ; *H NMR (DMSO-d6, 300 MHz) δ 11.05 (s, IH), 8.79 (s, IH), 8.62 (d, IH), 8.07 (s, IH), 7.96 (d, 2H), 7.81 (d, 2H), 7.75 (t, IH); 13 C NMR(DMSO-d6, 75 MHz) δ 161.3, 155.0 (d, J= 259 Hz), 146.4, 142.0 (q, J = 39 Hz), 139.9, 139.0 (d, J = 23 Hz), 133.1, 131.2 (d, J = 14 Hz), 124.9, 123.2, 120.5 (q, J = 262 Hz), 120.5, 116.7, 114.7, 109.9. Anal, calcd for d 7 H 9 F 4 N 5 O: C, 54.40; H, 2.41; N, 18.66. Found: C, 54.47; H, 2.52; N, 18.49. Example 301 2-fluoro-N-(4-(5-(2-furyl)-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)benzamide Example 301 A 5-(2-furyD- 1 -(4-nitrophenyl)-3-(trifluoromethyl)- lH-pyrazole 4-Nitrophenylhydrazine (7.75 g, 50.5 mmol) in a mixture of absolute ethanol (75 mL) and concentrated ΗC1 (40 mL) was treated with 4,4,4-trifluoro-l-(2-furyl)-l,3-butanedione (12.5 g, 60.6 mmol) and heated to reflux for 2 hours. The reaction mixture was cooled to room temperature and diluted with hexanes/ethyl acetate (600 mL of a 1:1 mixture). The layers were separated, and the organic layer was washed with 1.0 N ΗC1 (3 x 100 mL) and then saturated brine solution. The resultant mixture was dried over Na 2 SO 4 , and concentrated in vacuo. Purification using silica gel chromatography (97:3 hexanes/ethyl acetate gradient to 95:5 hexanes/ethyl acetate) yielded a white amorphous solid (14.7 g, 90% yield). 'ΗNMR (300 MHz, CDC1 3 ) δ 8.33 (dt, 2H, J=9.3,2.7Hz), 7.62 (dt, 2H, J=9.0,2.7Hz), 7.45 (dd, IH, J=1.5, 0.6Hz), 6.92 (s, IH), 6.47 (dd, IH, J=3.6,1.5Hz), 6.39 (dd, IH, J=3.3,0.6Hz). Example 301B 4-15-(2-furyl)-3-(trifluoromethyl)- IH-pyrazol- 1 -yllaniline A solution of Example 301 A (1.2 g, 3.7 mmol) in isopropanol (80 mL) was treated with 10% Pd/C (400 mg) and placed under a hydrogen atmosphere (balloon). After 1.75 hours the reaction was complete and the mixture was filtered through a plug of diatomaceous -184- earth. Concentration in vacuo was followed by purification using silica gel chromatography (6: 1 hexanes/ethyl acetate) yielding a white amorphous solid (1.0 g, 92% yield). MS (ESI+) m/e 294 (M+l) + ; 'HNMR (300 MHz, CD 3 OD) δ 7.55 (dd, IH, J=1.8, 0.9 Hz), 7.13-7.08 (m, 2H), 6.95 (s, IH), 6.79 (m, 2H), 6.39 (dd, IH, J=3.3, 1.8 Hz), 5.93 (d, IH, J=3.6 Hz). Example 3012-fluoro-N-(4-(5-(2-furyl)-3-(trifluoromethyl)- IH-pyrazol- 1- yPphenyPbenzamide Example 301B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 171-172 °C; MS (DCI/NH3) m/e 433 (M+NH4)+; 416 (M+H)+; !H NMR (DMSO-d6, 300 MHz) δ 7.91 (m, 2H), 7.76 (dt, IH), 7.62-7.54 (m, 2H), 7.45 (ddd, 2H), 7.33 (dt, IH), 7.27 (ddd, IH), 7.02(s, IH), 6.45(dd, IH), 6.15(dd, IH); 13 C NMR (DMSO-d6, 75 MHz) δ 145.1, 144.2, 141.2, 138.1, 136.6, 134.4, 134.3, 131.32, 131.29, 127.9, 125.8, 125.7, 122.0, 117.5, 117.2, 112.6, 111.6, 104.5. Example 302 N-(4-(5-cyano-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-4-methyl- 1.2.3-thiadiazole-5- carboxamide Example 300D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 193-195 °C; MS (DCI/NH3) m/e 396 (M+NH 4 ) + ; H NMR (DMSO-d6, 300 MHz) δ 11.05 (s, IH), 8.07 (s, IH), 7.94 (d, 2H), 7.82 (d, 2H), 2.84 (s, 3H). Example 303 N-(4-(5-cyano-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)isonicotinamide Example 300D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 145-146 °C; MS (DCI/NH3) m/e 358 (M+l) + ; !H NMR (DMSO-d6, 300 MHz) δ 10.85 (s, IH), 8.83 (d, 2H), 8.09 (s, IH), 8.04 (d, 2H), 7.90 (d, 2H), 7.82 (d, 2H). -185- Example 304 N-(4-(5-cyano-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-3-fluoroisonicotinamide Example 300D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 161-162 °C; MS (DCI/NH3) m/e 393 (M+NH 4 ) + ; l R NMR (DMSO-d6, 300 MHz) δ 11.05 (s, IH), 8.79 (s, IH), 8.62 (d, IH), 8.07 (s, IH), 7.96 (d, 2H), 7.81 (d, 2H), 7.75 (t, IH); 13 C NMR(DMSO-d6, 75 MHz) δ 161.3, 155.0 (d, J= 259 Hz), 146.4, 142.0 (q, J = 39 Hz), 139.9, 139.0 (d, J = 23 Hz), 133.1, 131.2 (d, J = 14 Hz), 124.9, 123.2, 120.5 (q, J = 262 Hz), 120.5, 116.7, 114.7, 109.9. Anal, calcd for C 17 H 9 F 4 N 5 O: C, 54.40; H, 2.41; N, 18.66. Found: C, 54.47; H, 2.52; N, 18.49. Example 305 N-(4-(5-acetyl-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-2-fluorobenzamide Example 305A l-(4-nitrophenyl)-3-(trifluoromethyl)-lH-pyrazole-5-carboxylic acid Example 301 A (3.7 g, 11.6 mmol) in a mixture of tert-butanol (65 mL) and 0.5 N NaOΗ (35 mL) was treated with KMnO 4 (4.5 g, 28.5 mmol) and heated at 75 °C for 1 hour. The mixture was cooled to ambient temperature, and the second portion of KMnO 4 (4.5 g, 28.5 mmol) was added. After stirring for an additional 1 hour at 75 °C, the reaction mixture was cooled to ambient temperature and filtered through a thick plug of diatomaceous earth. The diatomaceous earth was washed with water (3 x 100 mL). The combined washes were concentrated to 50% of the original volume and acidified to pΗ=3 with 50% HCl solution. Next, the mixture was extracted with ethyl acetate (3 x 100 mL) and the combined extracts were dried over Na 2 SO 4 , and concentrated in vacuo. Purification using silica gel chromatography (75:20:5 hexanes/ethyl acetate/acetic acid gradient to 55:35: 10 hexanes/ethyl acetate/acetic acid) yielded a white amorphous solid (1.8 g, 51% yield) along with 1.3 g of the corresponding ketoacid intermediate. The ketoacid intermediate was resubmitted to the conditions above to produce additional carboxylic acid (300 mg, yield after resubmission 60%, unoptimized). MS (ESI-) m/e 300 (M-l) " ; -186- 'HNMR (300 MHz, DMSO-d 6 ) δ 8.32 (d, 2H, J= 8.8 Hz), 7.84 (d, 2H, J= 8.8 Hz), 7.16 (s, IH). Example 305B 7V-methoxy-N-mefhyl- 1 -(4-nitrophenyl)-3-(trifluoromethyl)- lH-pyrazole-5-carboxamide Example 305A (1.8 g, 5.9 mmol) in CΗ 2 C1 2 (25 mL, 0.2 M) was treated with N,0- dimethylhydroxylamine hydrochloride (674 mg, 6.9 mmol), EDC (1.1 g, 5.9 mmol), 4- methylmorpholine (1.6 mL, 14.6 mmol), and 1-hydroxybenzotriazole hydrate (742 mg, 5.5 mmol). The mixture was stirred for 14 hours, then washed with 10% aqueous ΝaHSO 4 . The organic layer was dried over Na 2 SO 4 , and concentrated in vacuo. Purification using silica gel chromatography (2:1 hexanes/ethyl acetate) yielded a white foam (1.8 g, 83% yield). MS (ESI+) m/e 345 (M+l) + ; 'HNMR (300 MHz, CDC1 3 ) δ 8.35 (ddd, 2H, J=8.7,3.0,1.8Hz), 7.68 (ddd, 2H, J=9.3, 2.7, 2.1Hz), 7.08 (s, IH), 3.64 (s, 3H), 3.31 (s, 3H). Example 305C l-(4-aminophenyl)-N-methoxy-N-methyl-3-(trifluoromethyl)-lH-pyrazole-5-carboxamide Example 305B (1.2 g, 3.5 mmol) in an ethanol/water mixture (36 mL, 2:1 ratio respectively) was treated with iron powder (1.2 g) and ammonium chloride (120 mg). The mixture was heated at 80 °C for 35 minutes. The mixture was diluted with ethyl acetate (20 mL) and filtered through a thin plug of diatomaceous earth and concentrated in vacuo. Purification using silica gel chromatography (1: 1 hexanes/ethyl acetate gradient to 1:2 hexanes/ethyl acetate) yielded a white foam (1.0 g, 94% yield). MS (ESI+) m/e 315 (M+l) + ; 'ΗΝMR (300 MHz, CD 3 OD) δ 7.16 (ddd, 2H, J=8.7,3.0, 2.1Hz), 7.02 (s, IH), 6.74 (ddd, 2H, J=9.0, 3.0, 2.4Hz), 3.58 (s, 3H), 3.20 (s, 3H). Example 305D 1-T 1 -(4-aminophenyl)-3-(trifluoromethyl)- lH-pyrazol-5-yl]- 1 -ethanone Example 305C (56 mg, 0.18 mmol) in TΗF (2 mL) was slowly added to methy llithium (330 μL of a 1.4 M solution in diethyl ether, 0.46 mmol) at 0 °C. The reaction was stirred at 0 °C for five minutes then 10% aqueous ΝaΗSO 4 was added. The aqueous layer was back extracted with ethyl acetate (3 x 5 mL) and the combined extracts were concentrated in vacuo. -187- The mixture was purified by silica gel chromatography (1: 1 hexanes/ethyl acetate) to yield a white foam (36 mg, 75% yield). MS (ESI+) m/e 270 (M+l) + ; 'HNMR (300 MHz, DMSO-d 6 ) δ 7.72 (s, IH), 7.06 (ddd, 2H, J=8.4, 3.0, 2.1Hz), 6.58 (ddd, 2H, J=8.7, 3.0, 2.1Hz), 5.47 (s, 2H), 2.49 (s, 3H). Example 305 N-(4-(5-acetyl-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-2-fluorobenzamide Example 305 D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 188-189 °C; MS (ESI+) m/e 393 (M+l) + ; 'HNMR (400 MHz, DMSO-d 6 ) δ 10.93 (s, IH), 8.78 (d, IH, J=1.6Hz), 8.62 (dd, IH, J=4.8, 1.2Hz), 7.86 (s, IH), 7.82 (ddd, 2H, J=8.8, 6.8, 2.8Hz), 7.74 (t, IH, J=5.3Hz), 7.50 (ddd, 2H, J=8.8, 7.2, 3.2Hz), 2.57 (s, 3H); 13 CNMR (100 MHz, DMSO- d 6 ) δ 187.8, 161.0, 156.3, 153.7, 146.4, 141.2, 141.0, 140.6, 139.0, 138.9, 135.4, 131.4, 131.2, 126.5, 123.2, 122.2, 119.7, 119.6, 111.1, 28.8; Anal, calcd for C I8 H 12 F 4 N 4 O 2 : C, 55.11; H, 3.08; N, 14.28. Found: C, 55.05; H, 3.33; N, 13.71. Example 306 N-(4-(5-cyano-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-2-fluoronicotinamide Example 300D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 150-15TC; MS (DCI/NH3) m e 393 (M+NH 4 ) + ; iH NMR (DMSO-d6, 300 MHz) δ 10.96 (s, IH), 8.44 (d, IH), 8.30 (td, IH), 8.09 (s, IH), 7.97 (d, 2H), 7.82 (d, 2H), 7.59-7.52 (m, IH). Example 307 N-(4-(5-cyano-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2.3.5-trifluorobenzamide Example 300D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH 3 ) m/e 428 (M + NH4)+; -188- *H NMR (DMSO-d 6 , 300 MHz) δ 10.99 (s, IH), 8.09 (s, IH), 7.96 (d, 2H), 7.83 (s, IH), 7.82 (d, IH), 7.9-7.50 (m, IH). Example 308 2-fluoro-N-(4-(5-(2-thienyl)-3-(trifluoromethyl)- IH-pyrazol- l-yl)phenyl)benzamide Example 308A l-(4-nitrophenyl)-5-(2-thienyl)-3-(trifluoromethyl)-lH-pyrazole Sodium methoxide ( 0.46g, 8.52 mmol) in diethyl ether (15 mL) was added dropwise to methyl trifluoroacetate (0.82 mL mL, 7.79 mmol) in diethyl ether (10 mL). 2-Acetyl- thiophene (1 g, 7.79 mmol) in diethyl ether (10 mL) was subsequently added, and the mixture was heated to reflux for 16 hours. After cooling to room temperature, the mixture was concentrated to dryness. The crude intermediate was taken into ethanol (20 mL), and then concentrated ΗC1 (5 mL) and 4-nitrophenylhydrazine (1.21 g, 7.79 mmol) were added followed by heating to reflux for 16 hours. The mixture was freed of solvent and used without additional purification. MS (DCI/NΗ3) m/e 310 (M+H) + (For aniline produced under analysis conditions.); *H NMR (DMSO-d6, 300 MHz) δ 8.38 (d, 2H), 7.78 (d, 2H), 7.72 (dd, IH), 7.40 (s, IH), 7.21 (dd, IH), 7.13 (dd, IH). Example 308B 4-r5-(2-thienyl)-3-(trifluoromethyl)- IH-pyrazol- 1-yllaniline The above intermediate was taken into ethanol/water (50 mL, 3: l/v:v), iron powder (3.04 g, 54.53 mmol) and ammonium chloride (0.41 g, 7.79 mmol) were added, and the mixture was heated to reflux for 1 hour. The mixture was filtered through diatomaceous earth (5 g) and freed of solvent. The product was purified by silica gel chromatography (37 g) eluting with 50% acetone in hexanes (v:v). Yield (0.36 g, 15% for three steps). MS (DCI/NΗ3) m/e 310 (M+H)+. Example 308 2-fluoro-N-(4-(5-(2-thienyl)-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)benzamide Example 308B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 154-156 °C; -189- MS (DCI/NH3) m/e 449 (M+NH4)+; 432 (M+H)+; iH NMR (DMSO-d6, 300 MHz) δ 10.75 (s, IH), 7.9 (d, 2H), 7.75-7.65 (m, IH), 7.7 (dd, IH), 7.65-7.55 (m, IH), 7.5 (d, 2H), 7.45-7.30 (m, 2H), 7.3 (s, IH), 7.25 (dd, IH), 7.1 (m, IH). Example 309 2-fluoro-N-(4-(5-(methylsulfanyl)-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)benzamide Examples 309 A- 1 and 309 A-2 5-(methylsulfanyl)-l-(4-nitrophenyl)-3-(trifluoromethyl)-lH-pyrazole and l-(4-nitrophenyl)-3-(trifluoromethyl)-lH-pyrazol-5-ol S-Methyl 4,4,4-trifluoro-3-oxothiobutyrate (2.76 mL, 0.02 mol) and p- nitrophenylhydrazine (3.06 g, 0.02 mol) were dissolved in ethanol 18 mL and 4M ΗCl/dioxane (18 mL). The solution was refluxed overnight. After cooling the reaction mixture to room temperature, it was partitioned between ether and water. The ether layer was extracted with saturated aquesous NaΗCO, (3x), washed with brine, dried over Na 2 SO 4 and evaporated to give 5-(methylsulfanyl)-l-(4-nitrophenyl)-3-(trifluoromethyl)-lH-pyrazole (Example 309A-1, 0.61 g, 10% yield). The NaΗCO 3 extractions were combined and washed with ether. The NaHCO 3 solution was then acidified with IN HCl to pH~5 and extracted with ether (3x). The ether extracts were combined, dried over Na 2 SO 4 and concentrated to give 1- (4-nitrophenyl)-3-(trifluoromethyl)-lH-pyrazol-5-ol (Example 309 A-2, 4.02 g, 74% yield). Example 309 A- 1: MS (DCI/NΗ3) m e 304 (M+H) + ; 1H NMR (DMSO-d6, 300 MHz) δ 8.44 (d, 2H), 7.94 (d, 2H), 7.18 (s, IH), 2.6 (s, 3H). Example 309 A-2: MS (DCI/NH3) m/e 291 (M+NH4)+; *H NMR (DMSO-d6, 300 MHz) δ 8.39 (d, 2H), 8.1 (d, 2H), 6.0 (s, IH). Example 309B 4-r5-(methylsulfanyl)-3-(trifluoromethyl)-lH-pyrazol-l-yllaniline Example 309 A- 1 was reduced with Fe powder as described previously to gave the title compound in 75% yield. MS (DCI/NΗ3) m/e 291(M+NH4)+; -190- J H NMR (DMSO-d6, 300 MHz) δ 7.12 (d, 2H), 6.9 (s, IH), 6.63 (d, 2H), 5.55 (s, 2H), 2.5 (s, 3H). Example 309 2-fluoro-N-(4-(5-(methylsulfanyl)-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)benzamide Example 309B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 162-163 °C; MS (DCI/NH3) m/e 413 (M+NH4)+; iH NMR (DMSO-d6, 300 MHz) δ 10.7 (s, IH), 7.91 (d, 2H), 7.7 (t, IH), 7.6 (m, IH), 7.55 (d, 2H), 7.37 (m, 2H), 7.02 (s, IH), 2.53 (s, 3H). Example 310 2-fluoro-N-(4-(5-(3-pyridinyl)-3-(trifluoromethyl)- 1 H-pyrazol- 1 - yPphenyPbenzamide Example 310A 4-r5-(3-pyridinyl)-3-(trifluoromethyl)- IH-pyrazol- 1-yllaniline Sodium methoxide ( 0.46g, 8.52 mmol) in diethyl ether (15 mL) was added dropwise to methyl trifluoroacetate (0.83 mL, 7.85 mmol) in diethyl ether (10 mL). 2-Acetyl-pyridine (0.88 mL, 7.85 mmol) in diethyl ether (10 mL) was then added, and the mixture was heated to reflux for 16 hours. The mixture was freed of solvent and then redissolved in ethanol (20 mL). Concentrated ΗC1 (5 mL) and 4-nitrophenylhydrazine (1.21 g, 7.85 mmol) were added, and the mixture was heated to reflux for 16 hours. A solvent change to ethanol/water (50 mL, 3:l/v:v) was performed, iron powder (3.04 g, 54.53 mmol) and ammonium chloride (0.41 g, 7.79 mmol) were added, and the mixture was heated to reflux for 1 hour. The reaction mixture was filtered through diatomaceous earth (5 g), and the filtrate was concentrated to dryness. The product was purified by silica gel chromatography (75 mL silica gel) eluting with 50% acetone in hexanes (v:v). Yield (0.57 g, 22% for three steps). MS (DCI/NΗ3) m/e 305 (M+H) + ; *H NMR (DMSO-d6, 300 MHz) δ 9.10 (m, IH), 8.59 (dd, IH), 8.26 (dt, IH), 7.70 (s, IH), 7.49 (m, IH), 7.28 (d, 2H), 6.67 (d, 2H), 5.60 (s, 2H), Example 310 2-fluoro-N-(4-(5-(3-pyridinyl)-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)benzamide -191- Example 310B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 138-140 °C; MS (DCI/NH3) m e 427 (M+H)+; ^ NMR (DMSO-d6, 300 MHz) δ 10.7 (s, IH), 8.6-8.6 (m, 2H), 7.8 (d, 2H), 7.7-7.65 (m, 2H), 7.65-7.55 (m, IH), 7.45-7.3 (m, 6H). Example 311 3-fluoro-N-(4-(5-(2-thienyP-3-(trifluoromethyP-lH-pyrazol-l-yl)phenyl)isonicotinamide Example 308B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 153-155 °C; MS (DCI/NH3) m/e 433 (M+H)+; iH NMR (DMSO-d6, 300 MHz) δ 11.0 (s, IH), 8.8 (s, IH), 8.6 (d, IH), 7.9 (d, 2H), 7.75 (t, IH), 7.6 (d, IH), 7.5 (d, 2H), 7.3 (s, IH), 7.25 (d, IH), 7.1 ( , IH). Example 312 N-(4-(5-methoxy-3-(trifluoromethyP- 1 H-pyrazol- 1 -yPphenyPisonicotinamide Example 312A methyl 1 -(4-nitrophenyP-3-(trifluoromethyP- lH-pyrazol-5-yl ether To a mixture of Example 309 A-2 (0.776 g, 2.84 mmol) and K^CO j (0.94 g, 6.8 mmol) in acetonitrile (10 mL) was added dimethyl sulfate (0.32 mL, 3.4 mmol). Then the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with ether and washed with brine. After evaporation of the solvent, the crude was passed through short silica gel plug eluting with methylene chloride to give the title compound (0.71 g, 88% yield). MS (DCI/NΗ3) m/e 305 (M+NH4)+; !H NMR (DMSO-d6, 300 MHz) δ 8.39 (d, 2H), 8.03 (d, 2H), 6.59 (s, IH), 4.08 (s, 3H). Example 312B 4- | " 5-methoxy-3-(trifluoromethyP- IH-pyrazol- 1 -yl] aniline Reduction of the nitro group of Example 312A with Fe powder gave the title compound in 82% yield. -192- MS (DCI NH3) m/e 275 (M+NH4)+; !H NMR (DMSO-d6, 300 MHz) δ 7.18 (d, 2H), 6.61 (d, 2H), 6.36 (s, IH), 5.41 (s, 2H), 3.94 (s, 3H) . Example 312 N-(4-(5-methoxy-3-(trifluoromethyl)-l H-pyrazol- 1-yPphenyPisonicotinamide Example 312B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 181-182 °C; MS (DCI/NH3) m/e 380 (M+NH4)+; IH NMR (DMSO-d 6 , 300 MHz) δ 10.61 (s, IH), 8.8 (d, 2H), 7.94 (d, 2H), 7.89 (d, 2H), 7.66 (d, 2H), 6.49 (s, IH), 4.02 (s, 3H). Example 313 2-fluoro-N-(4-(5-methoxy-3-(trifluoromethyP- 1 H-pyrazol- 1 -yPphenyPbenzamide Example 312B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 167-168 °C; MS (DCI/NH3) m/e 397 (M+NH4)+; *H NMR (DMSO-d6, 300 MHz) δ 10.61 (s, IH), 7.86 (d, 2H), 7.69 (t, IH), 7.64 (d, 2H), 7.6 (m, IH), 7.35 (m, 2H), 6.46 (s, IH), 4.01 (s, 3H). Example 314 N-(4-(5-methoxy-3-(trifluoromethyP- 1 H-pyrazol- 1 -yl)phenyl)-4-methyl- 1.2.3-thiadiazole-5- carboxamide Example 312B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 159-160 °C; MS (DCI/NH3) m/e 401 (M+NH4)+; iH NMR (DMSO-d6, 300 MHz) δ 10.92 (s, IH), 7.84 (d, 2H), 7.66 (d, 2H), 6.49 (s, IH), 4.01 (s, 3H), 2.84 (s, 3H). Example 315 -193- N-(4-(5-acetyl-3-(trifluoromethyP- 1 H-pyrazol- 1 -yl)phenyl)-2-fluoronicotinamide Example 305 D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 188-189 °C; MS (ESI+) m/e 393 (M+l) + ; 'HNMR (400 MHz, DMSO-d 6 ) δ 10.93 (s, IH), 8.78 (d, IH, J=1.6Hz), 8.62 (dd, IH, J=4.8, 1.2Hz), 7.86 (s, IH), 7.82 (ddd, 2H, J=8.8, 6.8, 2.8Hz), 7.74 (t, IH, J=5.3Hz), 7.50 (ddd, 2H, J=8.8, 7.2, 3.2Hz), 2.57 (s, 3H); 13 CNMR (100 MHz, DMSO-d 6 ) δ 187.8, 161.0, 156.3, 153.7, 146.4, 141.2, 141.0, 140.6, 139.0, 138.9, 135.4, 131.4, 131.2, 126.5, 123.2, 122.2, 119.7, 119.6, 111.1, 28.8; Anal, calcd for C 18 H ]2 F 4 N 4 O 2 : C, 55.11 ; H, 3.08; N, 14.28. Found: C, 55.05; H, 3.33; N, 13.71. Example 316 2-fluoro-N-(4-(5-(methylsulfanyl)-3-(trifluoromethyl)- IH-pyrazol- 1 -yPphenyPnicotinamide Example 309B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 167-168 °C; MS (DCI/NH3) m/e 414 (M+NH4)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.88 (s, IH), 8.43 (m, IH), 8.3 (m, IH), 7.9 (d, 2H), 7.58 (d, 2H), 7.55 (m, IH), 7.04 (s, IH), 2.55 (s, 3H). Example 317 2-fluoro-N-(4-(5-methoxy-3-(trifluoromethyP- 1 H-pyrazol- 1 -yPphenyPnicotinamide Example 312B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 153-154 °C; MS (DCI/NH3) m/e 398 (M+NH4) -; iH NMR (DMSO-d6, 300 MHz) δ 10.78 (s, IH ), 8.42 (m, IH), 8.29 (m, IH), 7.86 (d, 2H), 7.66 (d, 2H), 7.53 (m, IH), 6.48 (s, IH), 4.0 (s, 3H). Example 318 3-fluoro-N-(4-(3-(4-pyridinyP-5-(trifluoromethyP- IH-pyrazol- 1 -yPphenyPisonicotinamide -194- Example 318A 4-r3-(4-pyridinyP-5-(trifluoromethyP- IH-pyrazol- 1-yllaniline Sodium methoxide ( 2.6 g, 48.1 mmol) in diethyl ether (30 mL) was added dropwise to methyl trifluoroacetate (4.1 mL, 40.8 mmol) in diethyl ether (10 mL). 4-Acetylpyridine (4.58 mL, 41.3 mmol) in diethyl ether (10 mL) was then added, and the mixture was heated to reflux for 16 hours. The mixture was freed of solvent and then redissolved in ethanol (200 mL). Concentrated ΗC1 (41 mL) and 4-nitrophenylhydrazine (6.3 g, 41.2 mmol) were added, and the mixture was heated to reflux for 16 hours. A solvent change to ethanol/water (250 mL, 3: l/v:v) was performed, iron powder (10 g, 179 mmol) and ammonium chloride (2.5 g, 47.2 mmol) were added, and the mixture was heated to reflux for 1 hour. The reaction mixture was filtered through diatomaceous earth (50 g), and the filtrate was concentrated to dryness. The product was purified by silica gel chromatography (200 mL silica gel) eluting with 50% acetone in hexanes (v:v). Yield (2.26 g, 18% for three steps). MS (DCI/NΗ3) m/e 305 (M+H)+ l U NMR (DMSO-d6, 300 MHz) δ 8.70 (d, 2H), 7.90 (d, 2H), 7.80 (s, IH), 7.15 (d, 2H), 6.65 (d, 2H), 5.60 (s, 2H). Example 318 3-fluoro-N-(4-(3-(4-pyridinyl)-5-(trifluoromethyl)-l H-pyrazol- 1 -yPphenyPisonicotinamide Example 318A was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 148-152 °C; MS (DCI/NH3) m e 428 (M+H)+; !H NMR (DMSO-d6, 300 MHz) δ 11.05 (s, IH), 8.8 (d, IH), 8.7 (d, 2H), 8.4 (dd, IH), 7.9- 7.8 (m, 5H), 7.75 (t, IH), 7.65 (d, 2H); 13 C NMR (DMSO-d6, 75 MHz) δ 161.2, 156.7, 153.3, 150.4, 150.3, 148.6, 146.4, 146.3, 139.6, 139.1, 138.8, 138.3, 134.0, 126.7, 124.8, 132.2, 121.2, 120.2, 119.8, 117.6, 114.1, 107.7, 107.6; Anal, calcd for C 21 H 13 F 4 N 5 O: C, 59.02; H, 3.06; N.16.38. Found: C, 58.82; H, 3.20; N, 16.44. Example 319 N-(4-(5-ethoxy-3-(trifluoromethyP- IH-pyrazol- l-yl)phenyP-2- fluoronicotinamide Example 319A -195- 4-[5-ethoxy-3-(trifluoromethyl)-lH-pyrazol-l-yl1aniline Example 309 A-2 was alkylated as described in Example 312 A (substituting ethyl bromide for dimethyl sulfate). Yield, 65%. Subsequent reduction with iron powder supplied the aniline. Yield, 71%. MS (DCI/NΗ3) m/e 289 (M+NH4)+; !H NMR (DMSO-d6, 300 MHz) δ 7.18 (d, 2H), 6.62 (d, 2H), 6.34 (s, IH), 5.4 (s, 2H), 4.23 (q, 2H), 1.34 (t, 3H). Example 319 N-(4-(5-ethoxy-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-2-fluoronicotinamide Example 319A was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 152-153 °C; MS (DCI/NH3) m/e 412 (M+NH4)+; H NMR (DMSO-d6, 300 MHz) δ 10.3 (s, IH), 8.92 (m, IH), 8.28 (m, IH). 7.85 (d, 2H), 7.67 (d, 2H), 7.54 (m, IH), 6.48 (s, IH), 4.3 (q, 2H), 1.38 (t, 3H). Example 320 3-fluoro-N-(4-(5-(methylsulfanyl)-3-(trifluoromethyl)- IH-pyrazol- 1 - yPphenyPisonicotinamide Example 309B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 142-143 °C; MS (DCI/NH3) m/e 414 (M+NH4)+; *H NMR (DMSO-d6, 300 MHz) δ 8.79 (s, IH), 8.62 (d, IH), 7.9 (d, 2H), 7.76 (t, IH), 7.59 (d, 2H), 7.04 (s, IH), 2.58 (s, 3H). Example 321 3-fluoro-N-(4-(5-methoxy-3-(trifluoromethyl)-l H-pyrazol- 1 -yPphenyPisonicotinamide Example 312B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 160-161 °C; MS (DCI/NH3) m/e 398 (M+NH4)+; X H NMR (DMSO-d6, 300 MHz) δ 8.79 (s, IH), 8.61 (d, IH), 7.76 (d, 2H), 7.74 (t, IH), 7.68 (d, 2H), 6.49 (s, IH), 4.01 (s, 3H). -196- Example 322 N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)-l H-pyrazol- 1 -yPphenyPisonicotinamide Example 322A 5-(difluoromethoxy)-l-(4-nitrophenyP-3-(trifluoromethyl)-lH-pyrazole To a solution of Example 309 A-2 (1.00 g, 3.66 mmol) in dry dimethylformamide (10 mL) was added potassium carbonate (1.42 g, 10.3 mmol). This mixture was heated for 5 minutes at 80 °C, then chlorodifluoromethane was bubbled through the reaction mixture for 30 minutes will maintaining the temperature at 80 °C. Introduction of chlorodifluoromethane was stopped after 30 min, then the reaction mixture was heated an additional 30 min. The reaction mixture was partitioned between ether and water. The ether layer was separated and washed with brine, dried over sodium sulfate, filtered and concentrated to give the crude difluoromethoxyether (0.90g, 76% yield) which was sufficiently pure to use in the next step. MS (DCI/NΗ3) m/e 311 (M+NH4) " " (For corresponding aniline produced by analysis.); *H NMR (DMSO-d6, 300 MHz) δ 8.44 (d,2H), 7.98 (d, 2H), 7.2-7.68 (t, IH), 6.94 (s, IH). Example 322B 4-[5-(difluoromethoxy)-3-(trifluoromethyP- IH-pyrazol- 1-yllaniline A mixture of the Example 322A (0.90g, 2.79 mmol), iron powder (1.25 g) and ammonium chloride (0.125g) in ethanol (12 mL) and water (4 mL) was heated to 100 °C for 30 minutes. Then the reaction mixture was cooled to room temperature and partitioned between ether and brine. The ether layer was dried over sodium sulfate and concentrated to give the crude amine, which was dissolved in methylene chloride and passed through a short silica gel plug to give the pure amine (0.80g, 97% yield). MS (DCI/NΗ3) m/e 311 (M+NH4)+; iH NMR (DMSO-d6, 300 MHz) δ 7.18 (d, 2H), 7.11-7.59 (t, IH), 6.73 (s, IH), 6.65 (d, 2H), 5.55 (s, 2H). Example 322 N-(4-(5-(difluoromethoxy)-3-(trifluoromethyP- IH-pyrazol- 1 -yPphenyPisonicotinamide Example 322B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 154-155 °C; -197- MS (DCI/NH3) m/e 416 (M+NH4)+; l U NMR (DMSO-d6, 300 MHz) δ 8.8 (d, 2H), 7.99 (d, 2H), 7.88 (d, 2H), 7.65 (d, 2H), 7.16- 7.64 (t, IH), 6.84 (s, IH). Example 323 N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-4-methyl- 1.2.3- thiadiazole-5-carboxamide Example 322B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 122-123 °C; MS (DCI/NH3) m/e 437 (M+NH4)+; l H NMR (DMSO-d6, 300 MHz) δ 7.89 (d, 2H), 7.65 (d, 2H), 7.16-7.64 (t, IH), 6.84 (s, IH), 2.84 (s, 3H). Example 324 N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-2-fluoronicotinamide Example 322B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 149-150 °C; MS (DCI/NH3) m/e 434 (M+NH4)+; l H NMR (DMSO-d6, 300 MHz) δ 8.44 (m, IH), 8.28 (m, IH), 7.9 (d, 2H), 7.65 (d, 2H), 7.55 (m, IH), 7.16-7.64 (t, IH), 6.84 (s, IH). Example 325 N-(4-(5-chloro-3-(trifluoromethyP-l H-pyrazol- l-yl)phenyP-2-fluoronicotinamide Example 325A 5-chloro- 1 -(4-nitrophenyP-3-(trifluoromethyP- lH-pyrazole A slurry of Example 309 A-2 (4.63 g, 16.9 mmol) in phenylphosphinic dichloride (11.5 mL, 81.1 mmol) was heated to 145 °C for 48 hours in a sealed tube with stirring. The reaction mixture was cooled to room temperature and carefully poured into saturated sodium bicarbonate solution (300 mL). The aqueous layer was further basified with 1 N NaOΗ (50 mL). The aqueous layer was extracted with ether (2 x 300 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The crude oil was purified with -198- 93% hexane/7% ethyl acetate to afford the title compound as a light yellow oil (3.10 g, 63% yield). MS (DCI/NH 3 ) m/e 279 (M+NH 4 )+ (for the corresponding aniline produced in the analysis); l NMR (DMSO-d 6 , 300 MHz) δ 8.47(d, 2H), 8.02 (d, 2H), 7.44 (s, IH). Example 325B 4-r5-chloro-3-(trifluoromethyP- IH-pyrazol- 1-yllaniline The nitro group of Example 325A was reduced with by the iron reduction procedure described previously. MS (DCI/NΗ3) m e 279 (M + NH 4 )+; H NMR (DMSO-d6, 300 MHz) δ 7.19 (s, IH), 7.18 (d, 2H), 6.65 (d, 2H), 5.62 (s, 2H). Example 325 N-(4-(5-chloro-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyP-2-fluoronicotinamide Example 325B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH 3 ) m/e 402 (M + NH 4 )+; l NMR (DMSO-d6, 300 MHz) δ 10.91 (s, IH), 8.45 (d, IH), 8.30 (dt, IH), 7.93 (d, 2H), 7.63 (d, 2H), 7.57 (dt, IH), 7.31 (s, IH). Example 326 2-fluoro-N-(4-(5-nitro-3-(trifluoromethyP- 1 H-pyrazol- 1 -yPphenyPbenzamide Example 326A tert-butyl l-(4-nitrophenyP-3-(trifluoromethyl)-lH-pyrazol-5-ylcarbamate To a solution of Example 305 A (2.11 g, 6.96 mmol) in toluene (40.0 mL) was added triethylamine (1.5 mL, 10.4 mmol) followed by diphenylphosphorylazide (2.25 mL, 10.4 mmol) and tert-butanol (4.7 mL, 48.7 mmol). The resulting mixture was heated at 80 °C for 20 hours. The reaction mixture was cooled and concentrated. The crude oil was chromatographed with 25% ethyl acetate/75% hexane to afford the title compound as a thick yellow oil (2.59 g, 99% yield). MS (DCI/NΗ3) m/e 373 (M + H)+; l NMR (DMSO-d6, 300 MHz) δ 9.79 (s, IH), 8.45 (d, 2H), 7.88 (d, 2H), 6.88 (s, IH), 1.32 (s, 9H). -199- Example 326B tert-butyl 1 -(4-aminophenyP-3-(trifluoromethyP- lH-pyrazol-5-ylcarbamate The nitro group of Example 326A was reduced with by the iron reduction procedure described previously. MS (DCI/NΗ3) m/e 343 (M + H)+; *H NMR (DMSO-d6, 300 MHz) δ 9.16 (s, IH), 7.10 (d, 2H), 6.69 (s, IH), 6.64 (d, 2H), 1.33 (s, 9H). Example 326C tert-butyl 1 - ( 4- [(2-fluorobenzoyPaminolphenyl } -3 -(trifluoro methyl)- 1 H-pyrazol-5- ylcarbamate Example 326B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NΗ3) m/e 465 (M + H)+; iH NMR (DMSO-d6, 300 MHz) δ 10.66 (s, IH), 9.43 (s, IH), 8.10 (dt, IH), 7.89 (d, 2H), 7.70 (dt, IH), 7.51 (d, 2H), 7.50-7.29 (m, 2H), 6.79 (s, IH), 1.34 (s, 9H). Example 326 2-fluoro-N-(4-(5-nitro-3-(trifluoromethyl)-l H-pyrazol- 1-yPphenyPbenzamide To an ice cold (0 °C) flask containing Example 326C (25 mg, 0.054 mmol) was added sulfuric acid (1 mL). This mixture was stirred at room temperature for 30 min. 30% Hydrogen peroxide (0.5 mL) solution was then added and the resulting mixture was stirred at room temperature for 20 hours. The mixture was poured into saturated sodium bicarbonate solution (30 mL), and the aqueous layer was extracted with ethyl acetate (3 x 30 mL) The combined organic layers was dried over sodium sulfate, filtered and concentrated. The crude oil was purified by flash column chromatography with 10% ethyl acetate/90% hexane to afford the title compound as an oil (7 mg, 33% yield). MS (DCI/NH3) m/e 412 (M + NH 4 )+; iH NMR (DMSO-d6, 300 MHz) δ 10.76 (s, IH), 8.15 (s, IH), 7.91 (d, 2H), 7.75-7.58 (m, 3H), 7.67 (d, 2H), 7.43- 7.27 (m, 2H). Example 327 -200- N-(4-(5-(difluoromethoxy)-3-(trifluoromethyP-lH-pyrazol-l-yl)phenyP-3- fluoroisonicotinamide Example 322B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 135-136 °C; MS (DCI/NH3) m/e 434 (M+NH4)+; !H NMR (DMSO-d6, 300 MHz) δ 10.98(s, IH), 8.79 (s, IH), 8.62 (d, IH), 7.9 (d, 2H), 7.74 (t, IH), 7.66 (d, 2H), 7.16-7.66 (t, IH), 6.85 (s, IH). Example 328 N-(4-(5-chloro-3-(trifluoromethyP- 1 H-pyrazol- 1 -yPphenyP-3-fluoroisonicotinamide Example 325B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 128-129 °C; MS (DCI/NH 3 ) m/e 412 (M + NH 4 )+; Η NMR (DMSO-d6, 300 MHz) δ 11.03 (s, IH), 8.80 (s, IH), 8.63 (d, IH), 7.93 (d, 2H), 7.75 (t, IH), 7.67 (d, 2H), 7.32 (s, IH); 13 C NMR (DMSO-d 6 , 75 MHz) δ 161.2, 154.5, 146.4, 141.8, 139.4, 139.0, 132.6, 131.2, 129.1, 126.4, 123.3, 121.0, 120.3, 105.0; Anal, calcd for C 16 H 9 ClF 4 N 4 O: C, 49.95; H, 2.35; N, 14.56. Found: C, 50.07; H, 2.46; N, 14.47. Example 329 N-(4-(5-(difluoromethyl)-3-(3-pyridinyP- IH-pyrazol- l-yl)phenyl)-3-fluoroisonicotinamide Example 329A nicotinaldehyde /V-(4-nitrophenyl)hydrazone 3-Pyridine carboxaldehyde (3.69 mL, 0.04 mol), -nitrophenylhydrazine (6 g, 0.04 mol), 1 drop of acetic acid, and ethanol (150 mL) were combined. The slurry was heated at 100 °C for 12 hours with stirring. After it was cooled to room temperature, the yellow solid was filtered and dried to give the title compound (9.12 g 96%) which was pure enough to use in the next step. MS (DCI/NH3) m/e 243 (M+l) + ; -201- 1H NMR (DMSO-d6, 300 MHz) δ 11.45 (s, IH), 8.89 (d, IH), 8.59 (d, IH), 8.57-8.52 (m, IH), 8.16 (d, 2H), 8.08 (s, IH), 7.78 (dt, IH), 7.21 (d, 2H). Example 329B /V ~ -(4-nitrophenyl)-3-pyridinecarbohydrazonoyl chloride To a solution of the Example 329A (6 g, 0.025 mol) in DMF (10 mL) at 0 (1 C was added a solution of N-chlorosuccinimide (3.45 g, 0.026 mol, 1.05 eq) in N, N- dimethylformamide (15 mL) dropwise over 30 minutes. After addition, the resulting dark green mixture was stirred at room temperature for two hours. Then it was poured into ice water with stirring. The resulting light brown solid was filtered, and dried in a vacuum oven at 40 °C for 12 hours to give the title compound (4.9 g, 71% yield) as an orange solid which was used in the next step without additional purification. MS (DCI/NH3) m/e 277 (M+l) + ; iH NMR (DMSO-d6, 300 MHz) δ 10.91 (s, IH), 9.17 (d, IH), 8.68 (dd, IH), 8.32 (dd, IH), 8.20 (d, 2H), 7.61-7.53 (m, 3H). Example 329C methyl 1 -(4-nitrophenyl)-3-(3-pyridinyP- lH-pyrazole-5-carboxylate Example 329B (2.0 g, 7.2 mmol), methyl α-chloroacrylate (1.5 g, 10.8 mmol, 1.5 eq), toluene (15 mL), and triethylamine (2.5 mL,18 mmol, 2.5 eq) were combined and heated at 80°C for 8 hours. After cooling to room temperature, the mixture was diluted with ethyl acetate (30 mL), and washed with IN ΗC1 (30 mL), and saturated NaCl solution (30 mL). The organic portion was dried over Na j SO 4 , filtered, and concentrated in vacuo. This dark brown crude oil was purified by flash chromatography, using ethyl acetate-hexane (v/v, 3:7) to give the pyrazole (650 mg, 28%) as a brown oil. MS (DCI/NΗ3) m/e 243 (M+l) + ; *H NMR (DMSO-d6, 300 MHz) δ 9.19 (d, IH), 8.60 (dd, 1 H), 8.39 (d, 2H), 8.33 (dd, IH), 7.94 (d, 2H), 7.88 (s, IH), 7.50 (dd, IH). Example 329D ri-(4-nitrophenyl)-3-(3-pyridinyl)-lH-pyrazol-5-yllmethanol To a -78 "C solution of Example 329C (650 mg, 2.0 mmol) in TΗF (30 mL) was added DIBAL (IM soln in hexane, 6.7 mL, 6.7 mmol) dropwise with stirring. After two hours at -78 -202- "C, the mixture was warmed to 0 "C and stirred an additional two hours. After it was quenched with potassium sodium tartrate solution (30 mL), the resulting mixture was stirred at room temperature overnight. Then the reaction mixture was diluted with ethyl acetate (20 mL) and washed with brine solution (20 mL). The organic layer was dried over Na j SO,,, filtered and concentrated vacuo. The crude product was purified by flash chromatography, with ethyl acetate-hexane (v/v, 75:25) to give the alcohol (370 mg,60%) as an oil. MS (DCI/NH3) m/e 297 (M+l) + ; iH NMR (DMSO-d6, 300 MHz) δ 9.13 (d, IH), 8.59 (dd, IH), 8.42 (d, 2H), 8.29 (dd, IH), 8.09 (d, 2H), 7.50 (dd, IH), 7.19 (s, IH), 5.81 (t, 1 H), 4.67 (d, 2H). Example 329E l-(4-nitrophenyl)-3-(3-pyridinyP-lH-pyrazole-5-carbaldehyde Under an argon atmosphere, solid tetrapropylammoniumperruthenate (21 mg, 0.06 mmol) was added in one portion to a solution of Example 329D (350 mg,1.2 mmol) dissolved in dichloromethane (5 mL) and acetonitrile (0.5 mL). N-methylmorpholine N-oxide (208 mg,1.8 mmol) was then added followed by flame dried powdered molecular sieves (1 g). The resulting black mixture was stirred at room temperature for 18 hours. The mixture was diluted with 10 mL of dichloromethane and filtered through a short silica gel plug with ethyl acetate- hexane (v/v, 7:3) to afford the aldehyde (180 mg, 53% yield) as an oil. MS (DCI/NΗ3) m/e 295 (M+l) + ; *H NMR (DMSO-d6, 300 MHz) δ 9.93 (s, IH), 9.19 (d, IH), 8.63 (dd, IH), 8.43 (d, 2H), 8.36 (dd, IH), 8.04 (d, 2H), 7.99 (s, IH), 7.52 (dd, IH). Example 329F 3-r5-(1.3-dithiolan-2-yl)-l-(4-nitrophenyP-lH-pyrazol-3-yl1pyridine Example 329E (150 mg,0.51 mmol), a catalytic amount of p-toluenesulfonic acid (3 mg), 1,2-ethanediol (0.04 mL, 0.51 mmol) and toluene (50 mL) were combined and refluxed for 4 hours in a Dean-Stark apparatus. Then the solution was cooled to room temperature. The toluene solution was washed with NaΗCO 3 solution (20 mL) and brine (20 mL). The organic layer was separated, dried with Na^O,,, filtered and concentrated in vacuo to give the dithiane (135 mg,72%) as a crude yellow solid which was pure enough to use in the next step. MS (DCI/NH3) m/e 371 (M+l) + ; *H NMR (DMSO-d6, 300 MHz) δ 9.11 (d, IH), 8.57 (dd, IH), 8.43 (d, 2H), 8.27 (dd, IH), 7.97 (d, 2H), 7.48 (dd, IH), 7.29 (s, IH), 6.03 (s, IH), 3.48-3.36 (m, 2H), 3.10-3.04 (m, 2 H). -203- Example 329G 3-[5-(difluoromethyD- 1 -(4-nitrophenyP- lH-pyrazol-3-yllpyridine To a cold (0 °C) solution of l,3-dibromo-5,5-dimethylhydantoin (302 mg, 1.06 mmol) in anhydrous dichloromethane (5 mL) under argon atmosphere was added ΗF-pyridine (0.2 mL, 0.88 mmol), followed by Example 329F (130 mg, 0.35 mmol). The resulting red solution was stirred at 0 °C for 45 minutes, then diluted with dichloromethane (10 mL) and quenched with NaΗCO 3 solution (10 mL). The organic layer was separated and washed with more NaHCO, solution (10 mL) dried with Na 2 SO 4 , filtered and concentrated in vacuo to give 100 mg of black crude material. This crude product was purified by HPLC with ethyl acetate-hexane (v/v, 6:4) to give the difluoromethane (40 mg, 46%) as an oil. See Reference: Katzenellenbogen, J.A.; Sondej, S.C. J. Org. Chem. 1986, 51(18). 3508-3513. MS (DCI/NH3) m/e 317 (M+l) + ; iH NMR (DMSO-d6, 300 MHz) δ 9.19 (d, IH), 8.62 (dd, IH), 8.46 (d, 2H), 8.33 (dt, IH), 7.96 (d, 2H), 7.65 (s, IH), 7.52 (dd, IH), 7.49 (s, IH). Example 329H 4- 5-(difluoromethyl)-3-(3-pyridinyP- IH-pyrazol- 1-yllaniline The title compound was prepared by iron powder and ammonium chloride reduction as previously described. The product was used in the subsequent step without additional purification or charactherization. Example 329 N-(4-(5-(difluoromethyl)-3-(3-pyridinyl)-lΗ-pyrazol-l-yPphenyl)-3-fluoroisonicotinamide Example 329H was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 176-178 °C; MS (ESI-) m/e 408 (M-l) " ; iH NMR (DMSO-d6, 300 MHz) δ 9.14 (d, IH), 8.8 (d, IH), 8.64-8.58 (m, 2H), 8.48 (dd, IH), 8.29 (dt, IH), 7.92 (d, 2H), 7.75 (t, IH), 7.65 (d, 2H), 7.53-7.46 (m, 2H), 3.72 (t, IH). Example 330 N-(4-(5-cyano-3-(2-pyridinyP- 1 H-pyrazol- 1 -yl)phenyP-3-fluoroisonicotinamide -204- Example 330A 7V-(4-nitrophenyl)-2-pyridinecarbohydrazonoyl chloride This compound was obtained from 2-pyridinecarboxaldehyde 4-nitrophenylhydrazone in 84% yield using the methodology described in the preparation of Example 329A. MS (DCI) m/e 277 (M+ 1 ) + ; ^ NMR (DMSO-d 6 , 300 MHz) δ 10.93 (s, IH), 8.68 (d, IH), 8.21 (d, 2H), 7.93 (td, IH), 7.58 (d, 2H), 7.49 (dd, IH), 7.24 (d, IH). Example 330B 1 -(4-nitrophenyl)-3-(2-pyridinyP- lH-pyrazole-5-carbonitrile The title compound was prepared from Example 330A and 2-chloroacrylonitrile in 39% yield using methodology described in the preparation of Example 329. MS (DCI) m/e 292 (M+l) + ; *Η NMR (CDC13, 300 MHz) δ 8.70 (d, IH), 8.45 (d, 2H), 8.16-8.07 (m, 3H), 7.84 (td, IH), 7.80 (s, IH), 7.35 (dd, IH). Example 330C 1 -(4-aminophenyl)-3-(2-pyridinyP- lH-pyrazole-5-carbonitrile This material was prepared in 34% yield from Example 330B using methodology described in the preparation of Example 329. MS (DCI) m/e 262 (M+l) + ; *Η NMR (DMSO-d6, 300 MHz) δ 8.66 (d, IH), 8.03 (d, IH), 7.92 (td, IH), 7.82 (s, IH), 7.43-7.36 (m, 3H), 6.61 (d, 2H), 5.68 (s, 2H). Example 330 N-(4-(5-cyano-3-(2-pyridinyP- IH-pyrazol- l-yPphenyP-3-fluoroisonicotinamide Example 330C was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 118-1 19 °C; MS (DCI/NH3) m/e 385 (M+l) + ; iH NMR (DMSO-d6, 300 MHz) δ 8.8 (d, IH), 8.68 (dt, IH), 8.63 (dd, IH), 8.08 (d, IH), 7.99-7.92 (m, 4H), 7.85 (d, 2H), 7.77 (t, IH), 7.48-7.42 (m, IH). Example 331 N-(4-(5-cyano-3-(3-pyridinyP- IH-pyrazol- l-yl)phenyl)-4-methyl-1.2.3-thiadiazole-5- -205- carboxamide Example 331 A 1 -(4-nitrophenyl)-3-(3-pyridinyP- lH-pyrazole-5-carbonitrile The title compound was prepared in 32% yield using the methodology described in the preparation of Example 304 using 2-chloroacrylonitrile and the chlorohydrazone previously described in the preparation of Example 329. MS (DCI) m/e 292 (M+l) + ; !Η NMR (DMSO-d6, 300 MHz) δ 9.19-9.16 (m, IH), 8.66 (d, IH), 8.51 (d, 2H), 8.37-8.30 (m, IH), 8.23 (s, IH), 8.17 (d, 2H), 7.56 (dd, IH). Example 33 IB l-(4-aminophenyP-3-(3-pyridinyl)-lH-pyrazole-5-carbonitrile The title compound was prepared in 84% yield from the 331 A using methodology described in the preparation of Example 304. MS (DCI) m/e 262 (M+l) + ; *Η NMR (DMSO-d6, 300 MHz) δ 9.10 (d, IH), 8.25 (dt, IH), 7.95 (s, IH), 7.50 (dd, IH), 7.39 (d, 2H), 6.70 (d, 2H), 5.65 (s, 2H). Example 331 N-(4-(5-cyano-3-(3-pyridinyP- IH-pyrazol- l-yl)phenyP-4-methyl-1.2.3-thiadiazole-5- carboxamide Example 33 IB was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 215-218 °C; MS (ESI) m/e 386 (M-l) " , 388 (M+l) + ; 1H NMR (DMSO-d6, 300 MHz) δ 9.15 (d, IH), 8.63 (dd, IH), 8.30 (dt, IH), 8.10 ( s, IH), 7.95 (d, 2H), 7.85 (d, 2H), 7.54 (dd, IH), 2.80 (s, 3H). Example 332 N-(4-(5-bromo-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyP-3-fluoroisonicotinamide Example 332A 5-bromo- 1 -(4-nitrophenyl)-3-(trifluoromethyP- lH-pyrazole -206- Example 309 A-2 (442 mg, 1.62 mmol) and phosphorous tribromide (2.63, 9.17 mmol) were heated at 160 °C for 20 hours. The reaction mixture was cooled and saturated sodium bicarbonate solution (20 mL) was added cautiously over 30 minutes. The mixture was diluted further with bicarbonate solution (100 mL). The aqueous layer was extracted with ethyl acetate (2 x 150 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The crude oil was purified by flash chromatography using 95% hexane/5% ethyl acetate affording the title compound as a dark brown oil (467 mg, 86% yield). MS (DCI/NH 3 ) m/e 325 (M + NH 4 )+ (for aniline produced in analysis); J H NMR (DMSO-d 6 , 300 MHz) δ 8.45 (d, 2H), 7.98 (d, 2H), 7.43 (s, IH). Example 332B 4-f5-bromo-3-(trifluoromethyD- IH-pyrazol- 1-yllaniline The title compound was prepared by iron powder and ammonium chloride reduction as previously described. The product was used in the subsequent step without additional purification or charactherization. MS (DCI/NΗ 3 ) m/e 323 (M + NH 4 )+; ] H NMR (DMSO-d 6 , 300 MHz) δ 7.16 (d, 2H), 7.14 (s, IH), 6.67 (d, 2H), 5.60 (s, 2H). Example 332 N-(4-(5-bromo-3-(trifluoromethyl)-l H-pyrazol- l-yPphenyP-3-fluoroisonicotinamide Example 332B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 143-144 °C; MS (DCI/NH3) m/e 446 (M + NH 4 )+; 1H NMR (DMSO-d6, 300 MHz) δ 11.03 (s, IH), 8.80 (s, IH), 8.63 (d, IH), 7.92 (d, 2H), 7.76 (t, IH), 7.64 (d, 2H), 7.33 (s, IH); Anal, calcd for Cι 6 H 9 BrF 4 N 4 O: C, 44.77; H, 2.11; N, 12.95. Found: C, 44.43; H, 2.11; N, 12.95. Example 333 3-fluoro-N-(4-(5-nitro-3-(trifluoromethyl)-l H-pyrazol- 1 -yPphenyPisonicotinamide Example 333 A tert-butyl l-r4-(isonicotinoylamino)phenyl]-3-(trifluoromethyl)-lH-pyrazol-5-ylcarbamate -207- Example 326B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. MS (DCI/NH 3 ) m/e 483 (M + NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 10.95 (s, IH), 9.46 (s, IH), 8.79 (s, IH), 8.62 (d, IH), 7.87 (d, 2H), 7.74 (t, IH), 7.54 (d, 2H), 6.80 (s, IH), 1.33 (s, 9H). Example 333 3-fluoro-N-(4-(5-nitro-3-(trifluoromethyl)-l H-pyrazol- 1 -yPphenyPisonicotinamide A solution of Example 333A (100 mg, 0.215 mmol) in trifluoroacetic acid (2 mL) and methylene chloride (2 mL) was stirred at room temperature for 30 min. The solvent was removed in vacuo and the residue was dissolved in acetonitrile (1 mL). Sodium nitrate (300 mg) and copper sulfate were mixed together in a separate flask with acetonitrile (2 mL) and water (1 mL). The amine solution was added slowly over 5 minutes, then the resulting mixture was allowed to stir for 15 minutes. The reaction mixture was poured into saturated sodium bicarbonate solution (50 mL). The aqueous layer was extracted with ethyl acetate (2 x 50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography with 50% ethyl acetate/ 50% hexane to obtain the title compound (8 mg, 9% yield), mp 188-190 °C; MS (DCI/NH 3 ) m/e 413 (M + NH 4 )+; ! H NMR (DMSO-d 6 , 300 MHz) δ 11.01 (s, IH), 8.80 (s, IH), 8.63 (d, IH), 8.14 (s, IH), 7.89 (d, 2H), 7.76 (t, IH), 7.69 (d, 2H); Anal, calcd for Cι 6 H 9 F 4 N 5 O 3 : C, 48.61; H, 2.29; N, 17.71. Found: C, 48.89; H, 2.37; N, 17.38. Example 334 3-fluoro-N-(4-[5-nitro-3-(3-pyridinyP-lH-pyrazol-l-yllphenyllisonicotinamide Example 334 A l-(4-nitrophenyl)-3-(3-pyridinyl)-lH-pyrazol-5-amine 3-Oxo-3-pyridin-3-yl-propionitrile (3.57g, 24.4 mmol)[Chem. Abstr.; 60; 10689d; 1964] and p-nitrophenylhydrazine (3.74g, 24.4 mmol) were dissolved in ethanol (100 mL), treated with 4N ΗC1 in dioxane (61 mL) and refluxed for 2 hours. After cooling to ambient temperature and evaporation to dryness, the residue was partitioned between ethyl acetate and -208- IN sodium bicarbonate solution. After removal of the aqueous phase, the organic layer was dried over MgSO 4 and concentrated in vacuo to provide 5.57g (19.8 mmol, 81%) of crude product. Silica gel chromatography of the crude product eluting with hexanes-acetone (4 step gradient from 6: 1 to 1: 1) provided 3.59g (12.8 mmol, 52.5%) of pure product as an oil. MS (ESI-) m/e 280 (M-H) ' ; !H NMR (DMSO-d6, 300 MHz) δ 9.02 (dd, J=0.5, 2Hz, IH), 8.54 (dd, J=2,5Hz, IH), 8.37 (dm, J=9Hz, 2H), 8.17 (dt, J=8,2Hz, IH), 8.04 (dm, J=9Hz, 2H), 7.46 (dd, J=5,8Hz, IH), 6.11 (s, IH), 5.92 (s, 2H). Example 334B r4-nitro-[3-(3-pyridyl)-5-(bis-Boc-amino)-l H-pyrazol- l-yl " | " [benzene Example 334A (0.66g, 2.35 mmol) was dissolved into dioxane (5 mL) and treated with di-t-butyldicarbonate (0.62g, 2.82 mmol) and a catalytic amount of 4- (dimethylamino)pyridine at 60 °C for 1 day. Additional di-t-butyldicarbonate (0.62g, 2.82 mmol) and 4-(dimethylamino)pyridine were introduced at 60 "C for 3 hours to completely consume the starting material. The solvent was evaporated in vacuo and the residue was purified by chromatography on silica gel (Biotage 40S) eluting with hexanes-acetone (step gradient 9: 1 to 2: 1) to provide 537 mg (1.41 mmol, 48%) of pure product as the bis-Boc material (some mono-Boc product was sometimes also present and was combined with the bis-Boc product for the subsequent reactions). MS (ESI-) m/e 380 (M-H) " ; MS (ESI+) m/e 482 (M+H) + ; !H NMR (DMSO-d6, 300 MHz) δ 9.14 (d, J=2Hz, IH), 8.62 (dd, J=2,5Hz, IH), 8.52 (dm, J=9Hz, 2H), 8.29 (dt, J=8,2Hz, IH), 7.78 (dm, J=9Hz, 2H), 7.53 (dd, J=5,8Hz, IH), 7.33 (s, IH), 1.29 (s, 18H). Example 334C r4-nitro-[3-(3-pyridyl)-5-(bis-Boc-amino)-lH-pyrazol-l-yinbenzene Example 334B (525 mg, 1.11 mmol) was dissolved in ethanol (10 mL) and water (0.5 mL) and reduced with iron and ammonium chloride as described previously to provide 375 mg (0.83 mmol, 75%) as a mixture of mono and bis-Boc protected product which was used directly in the subsequent amide coupling reactions. MS (ESI+) m/e 352(M+H) + (mono-Boc); (ESI-) m/e 452(M+H) + (bis-Boc); !H NMR (DMSO-d6, 300 MHz) δ 9.04 (d, J=2Hz, 0.33H), 9.02 (d, J=2Hz, 0.67H), 8.44 (s, 0.67H), 8.55-8.50 (m, IH), 8.62-8.14 (m, IH), 7.47-7.42 (m, IH), 7.15 (dm, J=9Hz, 1.33H), -209- 7.06 (dm, J=9Hz, 0.67H), 7.04 (s, 0.33H), 6.82 (s, 0.67H), 6.67-6.62 (m, 2H), 5.43 (s, 0.67H), 5.36 (s, 1.33H), 1.30-1.38 (m, 12H). Example 334D N- 4-[3-(3-pyridyl)-5-(bis-Boc-amino)-lH-pyrazol-l-yllphenyl1-3-fluoropyridin-4-yl- carboxamide Example 334C was processed as in Example (i)-a (Method 5, 6, or 7) to provide 530 mg of product as a mixture of mono and bis Boc protected substances. MS (ESI-) m/e 473(M-H) ' ; iH NMR (DMSO-d6, 300 MHz) δ 9.23 (s, 0.4H), 9.09 (d, J=2Hz, 0.6H), 9.06 (d, J=2Hz, 0.4H), 8.78 (s, IH), 8.62 (d, J=5Hz, IH), 8.58-8.54 (m, IH), 8.26-8.20 (m, IH), 7.92-7.84 (m, 2H), 7.76-7.73 (m, IH), 7.59 (dm, J=9Hz, 0.8H), 7.52-7.44 (m, 2.2H), 7.18 (s, 0.6H), 6.93 (s, 0.4H), 5.98 (s, 0.4H); Example 334E N- 4-r3-(3-pyridyl)-5-amino-lH-pyrazol-l-yllphenyll-3-fluoropyridin-4-yl-carboxamide Example 334E (530 mg) was treated with 4N HCl in dioxane (20 mL) for 1 hour. The excess reagent and solvent were removed by evaporation in vacuo, and the residue (0.60 g) was used without purification. MS (ESI-) m/e 373(M-H) ' ; 409(M+C1) " ; l H NMR (DMSO-d6, 300 MHz) δ 10.92 (s, IH), 9.15 (s, IH), 8.79 (s, IH), 8.72 (d, J=6Hz, IH), 8.67-8.62 (m, 2H), 7.89-7.85 (m, 2H), 7.74 (t, J=5Hz, IH), 7.66 (dm, J=9Hz, 2H), 6.14 (s, IH); Example 334 3-fluoro- V " - { 4-| " 5-nitro-3-(3-pyridinyD- IH-pyrazol- 1 -yllphenyl } isonicotinamide Example 334E (54 mg, 0.14 mmol) in 10% Η 2 SO 4 (1 mL) was added dropwise to NaNO 2 (400 mg) in water (2 mL) at 50 °C. The outgassing of the reaction stopped after approximately 15 minutes. The reaction was cooled to ambient temperature and diluted with IN NaHCO 3 solution. The product was extracted into ethyl acetate, the ethyl acetate layer was washed with water (2x) and dried over MgSO 4 . After evaporation of the solvent, the residue was purified by chromatography on silica gel (2g Alltech Extract-Clean™ silica) by elution with hexanes-ethyl acetate (1:2) to provide 17 mg (0.042 mmol, 30%) of the title compound as an off-white solid. -210- mp 213-215 °C; MS (ESI-) m/e 403(M-H) " ; 439(M+C1) " ; l R NMR (DMSO-d6, 300 MHz) δ 11.02 (s, lH) 9.19 (d, IH, J=2 Hz), 8.82 (s, IH), 8.62-8.66 (m, 2H), 8.35 (dt, IH, J=8,2 Hz), 8.22 (s, IH), 7.89 (d, 2H, J=9 Hz), 7.77 (t, IH, J=5 Hz), 7.69 (d, 2H, J=9 Hz), 7.53 (dd, IH, J=5,8 Hz). Example 335 N-(4-(5-bromo-3-(trifluoromethyP- IH-pyrazol- 1 -yl)phenyP-4-methyl- 1.2.3-thiadiazole-5- Example 332B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 145-147 °C; MS (DCI/NH3) m/e 451 (M + NH 4 )+; !H NMR (DMSO-d6, 300 MHz) δ 11.02 (s, IH), 7.90 (d, 2H), 7.64 (d, 2H), 7.32 (s, IH), 2.84 (s, 3H); Anal, calcd for C 14 H 9 BrF 3 N 5 OS: C, 48.61; H, 2.29; N, 17.71. Found: C, 48.89; H, 2.37; N, 17.38. Example 336 N- { 4-[5-chloro-3-(trifluoromethyP- IH-pyrazol- 1 -yl]phenyl 1 -3- fluoroisonicotinamide Example 336A l-(4-nitrophenyP-3-(trifluoromethyl)-lH-pyrazol-5-amine To a cold (0 °C) mixture of 2,2,2-trifluoro-N-(4-nitrophenyl)ethanehydrazonoyl chloride (161 mg, 0.60 mmol) and 5-aminotetrazole (51 mg, 0.60 mmol) in ethanol was added triethylamine (0.180 mL, 1.27 mmol). The resulting mixture was stirred at room temperature for one hour then heated to reflux for 4 hours. The reaction mixture was cooled and poured into saturated sodium bicarbonate solution (50 mL) and then extracted with ethyl acetate (3 x 50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The crude residue was purified using flash chromatography with 50% ethyl acetate / 50% hexane to afford the title compound as an oil (95 mg, 58% yield). MS (DCI/ΝΗ 3 ) m/e 274 (M+l) + ; 1H NMR (DMSO-d6, 300 MHz) δ 8.41 (d, 2H), 7.91 (d, 2H), 7.32 (s, 2H). Example 336B -211- 4-[5-chloro-3-(trifluoromethyl)-lH-pyrazol-l-yHanirine A solution of Example 336A (90 mg, 0.329 mmol) in acetonitrile (1 mL) was added to to a cold solution (0 °C) of copper chloride (66 mg, 0.49 mmol) and t-butyl nitrite (0.058 mL, 0.49 mmol) in acetonitrile (2 mL). The resulting mixture was stirred for 30 minutes, then poured into brine (50 mL). The aqueous layer was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The crude residue was purified by flash chromatography with 10% ethyl acetate/ 90% hexane to afford the chlorotriazole as an oil (70 mg, 73% yield). MS (DCI/NΗ,) m/e 280 (M+NΗ ,) + (For aniline produced by the analysis.); Η NMR (DMSO-d 6 , 300 MHz) δ 8.50 (d, 2H), 8.07 (d, 2 H). This nitro compound was subjected to the usual iron reduction conditions and used without purification in the next step. TLC analysis indicated that the reaction was complete. Example 336 N-f4-r5-chloro-3-(trifluoromethyP- IH-pyrazol- l-yllphenyU-3-fluoroisonicotinamide mp 167-170 °C; MS (DCI/NΗ 3 ) m/e 386 (M + H)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 11.08 (s, IH), 8.80 (s, IH), 8.63 (d, IH), 7.95 (d, 2H), 7.76 (d, 2H), 7.75 (s, IH). N-(4-(5-chloro-3-(trifluoromethyP- 1 H- 1.2.4-triazol- 1 -yl)phenyP-3-fluoroisonicotinamide Example 325B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 167-170 °C; MS (DCI/NH 3 ) m/e 386 (M + H)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 11.08 (s, IH), 8.80 (s, IH), 8.63 (d, IH), 7.95 (d, 2H), 7.76 (d, 2H), 7.75 (s, IH). Example 337 4-methyl-N-(4-(5-nitro-3-(3-pyridinyP- lH-pyrazol- 1 -v phenyP- 1.2.3-thiadiazole-5- Example 337A tert-bu yl l-(4-( r(4-methyl-1.2.3-thiadiazol-5-yl)carbonyllamino}phenyP-3-(3-pyridinyP-lH- pyrazol-5-ylcarbamate -212- The aniline used to prepare Example 334 (510 mg, 1.45 mmol) was was processed as in Example (i)-a (Method 5, 6, or 7) to provide 580 mg (1.21 mmol, 84%) of product that was used directly in the next step. MS (ESI-) m/e 476(M-H) " (mono-Boc); 576(M-H) " (bis-Boc); iH NMR (DMSO-d6, 300 MHz) δ 10.96 (s, 0.4H), 10.93 (s, 0.6H), 9.97 (s, 0.6H), 9.10 (D, J=2HZ, 0.4H), 9.06(d, J=2Hz, 0.6H), 8.61-8.54 (m, 1.4H), 8.26-8.20 (m, IH), 7.88 (d, J=9Hz, 0.8H), 7.83 (d, J=9Hz, 1.2H), 7.59 (d, J=9Hz, 1.2H), 7.52-7.45 (m, 1.4H), 7.42-7.37 (m, 0.4H), 7.18 (s, 0.4H), 6.93 (s, 0.6H), 2.83 (s, 3H). Example 337B /V-{4- 5-amino-3-(3-pyridinyl)-lH-pyrazol-l-yl1phenyl)-4-methyl-1.2.3-thiadiazole-5- carboxamide Example 337A (580 mg, 1.21 mmol) was treated with 4N ΗC1 in dioxane (20 mL) for 1 hour. The excess reagent and solvent were evaporated in vacuo to provide 0.71 mg of solid. The solid was partitioned between ethyl acetate and IN sodium bicarbonate solution, and the organic layer was further washed with water (2x) and dried over MgSO 4 to provide 363 mg (0.96 mmol, 79%) of product. MS (ESI+) m/e 378(M+Η) + ; l R NMR (DMSO-d6, 300 MHz) δ 10.91 (s, IH), 8.96 (d, J=2Hz, IH), 8.51 (d, J=5Hz, IH), 8.12 (d, J=8Hz, IH), 7.83 (d, J=9Hz, 2H), 7.67 (d, J=9Hz, 2H),7.42 (dd, J=5,8Hz, IH, 6.00 (s, IH), 5.54 (s, 2H), 2.83 (s, 3H). Example 337 N-[4-r3-(3-pyridyP-5-nitro-lH-pyrazol-l-yllphenyl1-4-methylthiadiazol-5-yl-carboxamide Example 337B (145 mg, 0.38 mmol) was dissolved in 10% H 2 SO 4 (1.5 mL) and added in portions over 1 minute to sodium nitrite (548 mg, 7.9 mmol) in 5.5 mL water. The mixture was allowed to react with vigorous stirring for 5 minutes at 60 °C. The reaction was quenched by the addition of IN sodium bicarbonate solution, and the product was extracted into ethyl acetate followed by concentration in vacuo. Additional purification was achieved chromatographically with an Alltech Extract-Clean™ cartridge eluting with ethyl acetate to provide 30 mg (0.073 mmol, 19%) of the title compound, mp 208-210 °C; MS (ESI-) m e 406(M-H) " ; -213- l R NMR (DMSO-d6, 300 MHz) δ 9.18 (d, IH, J=2 Hz), 8.63 (dd, IH, J=2,5 Hz), 8.33 (dt, IH, J=8,2 Hz), 8.20 (s, IH), 7.87 (d, 2H, J=9 Hz), 7.69 (d, 2H, J=9 Hz), 7.53 (dd, IH, J=5,8 Hz), 2.86 (s, 3H). Example 338 N-(4-(5-cyano-3-( 1.3-thiazol-2-yP- 1 H-pyrazol- 1 -yl)phenyP-3-fluoroisonicotinamide Example 338A 1.3-thiazole-2-carbaldehyde N-(4-nitrophenyl)hydrazone The hydrazone was prepared from 4-nitrophenylhydrazine and 2- thiazolecarboxaldehyde in 88% yield using the methodology described in the preparation of Example 300A. MS (DCI) m/e 249 (M+l) + ; !H NMR (DMSO-d6, 300 MHz) δ 8.21 (s, IH), 8.09 (d, 2H), 7.88 (d, IH), 7.69 (d, IH), 7.09 (d, 2H). Example 338B /V-(4-nitrophenyD- 1.3-thiazole-2-carbohydrazonoyl chloride The chlorohydrazone was prepared in 88% yield from the hydrazone prepared above using methodology described in the preparation of Example 300B. MS (DCI) m/e 283 (M+l) + ; *H NMR (DMSO-d6, 300 MHz) δ 11.10 (s, IH), 8.24 (d, 2H), 7.96 (d, IH), 7.92 (d, IH), 7.48 (d, 2H). Example 338C 1 -(4-nitrophenyl)-3-( 1.3-thiazol-2-yP- lH-pyrazole-5-carbonitrile The title compound was prepared in 15% yield using the chlorohydrazone prepared above and the reagents and methodology described in the preparation of Example 300C. MS (DCI) m/e 298 (M+l) + ; 1H NMR (DMSO-d6, 300 MHz) δ 8.51 (d, 2H), 8.15 (d, 2H), 8.09 (s, IH), 8.04 (d, IH), 7.97 (d, IH). Example 338D 1 -(4-aminophenyl)-3-( 1.3-thiazol-2-yP- lH-pyrazole-5-carbonitrile The compound was prepared in 36% yield from the nitrophenyl compound prepared above using the methodology described in the preparation of Example 300D. MS (ESI) m/e 268 (M+l) + , 266 (M-l)\ -214- 1H NMR (DMSO-d6, 300 MHz) δ 7.97 (d, IH), 7.83 (d, IH), 7.81 (s, 1H),7.38 (d, 2H), 6.70 (d, 2H), 5.68 (s, 2H). Example 338 N-(4-(5-cyano-3-( 1.3-thiazol-2-yP- 1 H-pyrazol- 1 -yl)phenyl)-3-fluoroisonicotinamide Example 338D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 210-211 °C; MS (ESI) m/e 389 (M-l) " , 391 (M+l) + ; 1H NMR (DMSO-d6, 300 MHz) δ 11.04 (s, IH), 8.80 (d, IH), 8.63 (dd, IH), 8.00 (d, IH), 7.97 (d, 2H), 7.89 (d, IH), 7.84 (d, 2H), 7.76 (t, IH). Example 339 N-(4-(3-(5-bromo-3-pyridinyl)-5-(difluoromethoxy)- 1 H-pyrazol- 1 -yPphenyl)-3- fluoroisonicotinamide Example 339A 3-(5-bromo-3-pyridinyP- 1 -(4-nitrophenyP- lH-pyrazol-5-ol Condensation of methyl 5-bromonicotinoylacetate and p-nitrophenylhydrazine using methodology previously described gave the title compound in quantitative yield. MS (APCI) m/e 361 (M+Η)+; 1H NMR (DMSO-d6, 300 MHz) δ 9.1 (d, IH), 8.73 (d, IH), 8.52 (t, IH), 8.38 (d, 2H), 8.22 (d, 2H), 6.33 (s, IH). Example 339B 3-bromo-5-[5-(difluoromethoxy)-l-(4-nitrophenyl)-lH-pyrazol-3-yl1pyridine This intermediate was prepared by alkylation of Example 339A in 81% yield using the procedure described in the preparation of Example 322A. MS (DCI/NΗ3) m/e 430 (M+NH4)+; !H NMR (DMSO-d6, 300 MHz) δ 9.4 (d, IH), 8.75 (d, IH), 8.57 (t, IH), 8.44 (d, 2H), 8.07 (d, 2H), 7.66-7.18 (t, IH), 7.14 (s, IH). Example 339C -215- 4-r3-(5-bromo-3-pyridinyl)-5-(difluoromethoxy)- IH-pyrazol- 1-yllphenylamine This intermediate was prepared by reduction of the above compound with iron powder in 82% yield as described in the preparation of Example 322B. MS (DCI/NΗ3) m/e 400 (M+NH4)+; iH NMR (DMSO-d6, 300 MHz) δ 9.04 (d, IH), 8.67 (d, IH), 8.45 (t, IH), 7.54-7.06 (t, IH), 7.22 (d, 2H), 6.93 (s, IH), 6.65 (d, 2H), 5.47 (s, 2H). Example 339 N-(4-(3-(5-bromo-3-pyridinyl)-5-(difluoromethoxy)-l H-pyrazol- l-yl)phenyP-3- fluoroisonicotinamide Example 339C was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 179-180 °C; MS (DCI/NH3) m/e 506 (M+H)+; iH NMR (DMSO-d6, 300 MHz) δ 10.94 (s, IH), 9.1 (d, IH), 8.8 (s, IH), 8.72 (d, IH), 8.62 (d, IH), 8.51 (t, IH), 7.9 (d, 2H), 7.74 (t, IH), 7.71 (d, 2H), 7.13-7.61 (t, IH), 7.05 (s, IH). Example 340 N-f 4-f 5-cy ano-3-f 1.3-thiazol-2-yl IH-pyrazol- 1 -yl)phenyl)-4-methyl- 1.2.3-thiadiazole-5- carboxamide Example 338D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 230°C; MS (ESI-) m/e 392 (M-l) " ; iH NMR (DMSO-d6, 300 MHz) δ 8.10 (d, IH), 7.96 (d, 2H), 7.97 (s, IH), 7.89 (d, IH), 7.85 (d, 2H), 2.86 (d, 3H). Example 341 N-(4-(5-cyano-3-( 1.3-thiazol-2-yP- IH-pyrazol- 1 -yPphenyl)-3-fluoroisonicotinamide Example 338D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 162-163 °C; MS (DCI/NH3) m/e 434 (M+l) + ; -216- iH NMR (DMSO-d6, 300 MHz) δ 11.06 (s, IH), 8.80 (d, IH), 8.63 (dd, IH), 8.00 (d, IH), 7.93 (d, 2H), 7.87 (d, IH), 7.78 (t, IH), 7.66 (d, 2H), 7.62 (s, IH); IR(KBr)cm' 3277,3102, 1653, 1604, 1541, 1516, 1416, 1389, 1325, 1295, 1247, 1168, 1125,990,934,844,726. Example 342 4-methyl-N-(4-(3-( 1.3-thiazol-2-yP-5-(trifluoromethvP- 1 H-pyrazol- 1 -yPphenyP- 1.2.3- thiadiazole-5-carboxamide Example 342A 4.4.4-trifluoro- 1 -( 1.3-thiazol-2-yP- 1.3-butanedione. sodium salt To a slurry of sodium methoxide (5.2 g, 96 mmol) in ethyl ether (250 mL) under nitrogen was added methyl trifluoroacetate (9.66 mL, 96 mmol) slowly with stirring. The resulting white slurry was stirred at room temperature for 30 minutes. It was cooled to 0 °C and 2- acetylthiazole (8.28 mL, 80 mmol) was added dropwise to the mixture. This slurry became a clear solution upon addition of 2-acetylthiazole. Then the mixture was heated to reflux for 1 hour. This resulting reddish slurry was cooled to room temperature and ethyl ether was removed in vacuo to give the diketone product (17.80g, quantitative) as an off white solid. This crude product was not further purified before the next step. MS (ESI) m/e 222 (M-l) " ; ! H NMR (DMSO-d6, 300 MHz) δ 7.88 (d, IH), 7.84 (d, IH), 6.39 (s, IH). Example 342B 2-[5-(trifluoromethyl)-lH-pyrazol-3-yP-1.3-thiazole Example 342A (4.8 g, 22 mmol), anhydrous hydrazine (1.28 mL, 26.4 mmol), and dry toluene (100 mL) were combined and heated to reflux for 3 hours. The reaction mixture was cooled to room temperature and the toluene was removed in vacuo. This crude material was purified by flash chromatography, eluting with ethyl acetate-hexanes (v/v, 3:7) to give the desired pyrazole product (1.8 g, 38%). MS (DCI/NΗ3) m/e 220 (M+l)+; *H NMR (DMSO-d6, 300 MHz) δ 10.52 (s, IH), 8.02 (d, IH), 7.49 (d, IH), 7.25 (s, 1H),6.98 (s, IH). Example 342C -217- 2- 1 -(4-nitrophenyl)-5-(trifluoromethyP- lH-pyrazol-3-yll- 1 ,3-thiazole To a cooled (0 °C) slurry of sodium hydride (95%, 432 mg, 17 mmol) and dry DMF (20 mL) was added dropwise Example 342B (3.4 g, 16 mmol) in dry DMF (5 mL). The resulting mixture was stirred for 10 minutes, 4-fluoronitrobenzene (1.80 mL, 17 mmol) was also added dropwise to the reaction mixture at 0 °C. After addition, the mixture was heated to reflux for 3 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, partitioned between 30 mL of ethyl acetate (30 mL) and water (20 mL). The organic layer was separated, dried with Na 2 SO 4 , filtered and concentrated in vacuo to give a mixture of regioisomers (5 g, 91%, 2: 1 mixture of regioisomers). This crude material was not purified before next iron reduction step. MS (ESI) m/e 341 (M+l) + ; Compound 1: 1Η NMR (DMSO-d6, 300 MHz) δ 8.36 (d, 2H), 7.97 (d, IH), 7.91 (d, IH), 7.82 (d, 2H), 7.66 (s, IH); Compound 2: IH NMR (DMSO-d6, 300 MHz) δ 8.47 (d, 2H), 8.02 (d, IH), 7.95 (d, 2H), 7.89 (d, IH), 7.73 (s, IH). Example 342D 4-f3-(1.3-thiazol-2-yl)-5-(trifluoromethyP- IH-pyrazol- 1-yllaniline Iron powder (5.75 g, 103 mmol), ammonium chloride( 595 mg, 12 mmol), Example 342C (isomeric mixture from previous step, 5g, 15 mmol) and ethanol-Η 2 O (4: 1, 50 mL) were combined. This resulting black mixture was heated to reflux for 8 hours. The reaction mixture was cooled to room temperature, passed through a diatomaceous earth pad and a silica gel plug, eluting with ethyl alcohol. After the desired fractions was combined and concentrated in vacuo, the residue was diluted with dichloromethane (20 mL) and washed with NaHCO 3 (20 mL X 2). The organic portion was dried with Na^O,,, filtered and concentrated in vacuo. This brown crude product was purified by flash chromatography, eluting with ethyl acetate- hexanes (v/v, 2:8) to give the desired product as a pale white solid (1.5 g, 33% yield). MS (ESI) m/e 311 (M+l)\ 309 (M-l) " ; !H NMR (DMSO-d6, 300 MHz) δ 7.97 (d, IH), 7.82 (d, IH), 7.49 (s, IH), 7.19 (d, 2H), 6.65 (d, 2H), 5.65 (s, 2H). Example 342 -218- 4-methyl-N-(4-(3-( 1 ■3-thiazol-2-yl)-5-(trifluoromethvP- lH-pyrazol- 1 -vPphenvP- 1.2.3- thiadiazole-5-carboxamide Example 342D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 162-163 °C; MS (ESI) m/e 437 (M+l) + , 435 (M-l) ' ; iH NMR (DMSO-d6, 300 MHz) δ 11.04 (s, IH), 8.00 (d, IH), 7.92 (d, 2H), 7.86 (d, IH), 7.65 (d, 2H), 7.62 (s, IH), 2.86 (s, 3H). Example 343 N-(4-(3-(2.4-dimethyl- 1 ■3-thiazol-5-vP-5-(trifluoromethyP- IH-pyrazol- 1 -yl)phenyP-3- fluoroisonicotinamide Example 343 A 4-[3-(2.4-dimethyl-1.3-thiazol-5-yP-5-(trifluoromethyP- IH-pyrazol- 1-yllaniline A mixture of sodium methoxide (2.10 g, 38.65 mmol), methyl trifluoroacetate (3.90 mL, 38.65 mmol) and 5-acetyl-2,4-dimethylthiazole (5.0 g, 32.2 mmol) in ether (150 mL) was heated at reflux for 16 hours. The reaction mixture was cooled and ether was removed in vacuo. Ethanol (100 mL), 4-nitrophenylhydrazine (4.92 g, 32.2 mmol) and concentrated ΗC1 (10 mL) were added and the resulting mixture was heated to reflux for 16 hours. The reaction mixture was cooled and iron powder (12.5 g, 225 mmol) was added and the mixture was heated at reflux for 2 hours. The reaction mixture was cooled and poured in saturated sodium bicarbonate solution (200 mL). The aqueous layer was extracted with ethyl acetate (3 x 150 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The residue was purified three times by flash chromatography using 15% isopropanol/ 85% hexane to afford (150 mg, 1.4% yield) the desired product. ! Η NMR (DMSO-d 6 , 300 MHz) δ 7.28 (s, IH), 7.14 (d, 2H), 6.64 (d, 2H), 5.60 (s, 2H), 2.61 (s, 3H), 2.51 (s, 3H). Example 343 N-(4-(3-(2.4-dimethyl- 1 ■3-thiazol-5-yl)-5-(trifluoromethyP- lH-pyrazol- 1 -yl)phenvP-3- fluoroisonicotinamide Example 342D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. -219- mp 194-195 °C; MS (DCI/NH3) m/e 462 (M + H)+; !H NMR (DMSO-d6, 300 MHz) δ 11.01 (s, IH), 8.80 (s, IH), 8.62 (d, IH), 7.91 (d, 2H), 7.75 (t, IH), 7.60 (d, 2H), 7.41 (s, IH), 2.63 (s, 3H), 2.51 (s, 3H). Example 344 3-fluoro-N-(4-(5-(l -methyl- lH-pyrrol-3-yP-3-(trifluoromethyl)- IH-pyrazol- 1- yPphenyPisonicotinamide Example 344A 4- \5-( 1 -methyl- lH-pyrrol-3-yP-3-(trifluoromethyP- IH-pyrazol- 1 -yllphenylamine 3-Acetyl-l -methyl pyrrole (5 g, 40.65 mmol), sodium methoxide (2.6 g, 48.15 mmol) and methyl trifluoroacetate (4.9 mL, 48.15 mmol) were combined with diethyl ether (200 mL). The mixture was heated to reflux for 2 hours. After cooling to room temperature, solvent was removed. Hydrazine monohydrate (2.16 mL, 44.58 mmol) and toluene (150 mL) were added, and the reaction mixture was heated to reflux for 16 hours. Upon cooling to room temperature, solvent was once again removed. The crude material was dissolved in dimethylformamide (100 mL) and cooled to 0 °C. This solution was added dropwise to a mixture of sodium hydride (60% in mineral oil, 1.79g, 44.72 mmol) in dimethylformamide (30 mL). After stirring at 0 °C for 30 minutes, l-fluoro-4-nitrobenzene (4.3 mL, 40.65 mmol) was added. The resulting mixture was warmed to 90 °C for 16 hours. After cooling to 0 °C, the reaction was quenched with water (5 mL). The quenched mixture was partitioned between ethyl acetate (100 mL) and water (100 mL). The aqueous layer was back extracted with ethyl acetate (2 x 100 mL). The organic layers were combined, washed with brine (2 x 100 mL), dried over magnesium sulfate and concentrated to dryness. Iron powder (15.6 g, 0.28 mol), ammonium chloride (2.26 g, 40.65 mmol) and a mixture of ethanol water (200 mL, 3: l/v:v) were added to the crude intermediate. The mixture was heated to reflux for 1 hour. After cooling to ambient temperature, the reaction mixture was passed through a pad of diatomaceous earth (20 g). The filtrate was concentrated to dryness. The crude product was purified by silica gel chromatography eluting with 40% acetone in hexanes (v:v). Fractions containing the desired product were combined and freed of solvent (2.11 g, 17 % yield). MS (DCI/NH3) m/e 307 (M+H)+; !H NMR (DMSO-d6, 300 MHz) δ 7.01 (d, 2H), 7.95 (s, IH), 6.72 (t, IH), 6.60 (d, 2H), 6.37 (t, IH), 5.85 (m, IH), 5.53 (s, 2H), 3.53 (s, 3H) -220- Example 344 3-fluoro-N-(4-(5-(1 -methyl-lH-pyrrol-3-yP-3-(trifluoromethyl)-lH-pyrazol-l- yPphenyPisonicotinamide Example 344A was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 171-173 °C; MS (DCI/NH3) m/e 430 (M+H)+; !H NMR (DMSO-d6, 300 MHz) δ 8.80 (d, IH), 8.60 (dd, IH), 7.85 (d, 2H), 7.45 (d, 2H), 7.22 (s, IH), 6.91 (s, IH), 6.75 (m, IH), 6.70 (t, IH), 5.80 (m, IH), 3.55 (s, 3H). Example 345 3-fluoro-N-(4-(3-tetrahydro-2-furanyl-5-(trifluoromethyl)-l H-pyrazol- 1- yPphenyPisonicotinamide Example 345A 3-(2-furyl)-5-(trifluoromethyl)-lH-pyrazole 4,4,4-Trifluoro-l-(2-furyl)-l,3-butanedione (0.9 g, 4.39 mmol) and hydrazine monohydrate (0.19 mL, 4.82 mmol) were combined in toluene (10 mL) and refluxed overnight. After cooling to room temperature, solvent was removed in vacuo. The product (0.77 g, 87 % crude yield) was used without further purification. !Η NMR (DMSO-d6, 300 MHz) δ 7.85 (m, IH), 7.00 (s, IH), 6.95 (d, IH), 6.67 (m, IH). Example 345B 3-(2-furyP- 1 -(4-nitrophenyP-5-(trifluoromethyP- lH-pyrazole To a mixture of sodium hydride (60% in mineral oil, 0.193 g, 4.83 mmol) and dimethylformamide (10 mL) under nitrogen at 0 °C was added dropwise the Example 345 A (0.89 g, 4.41 mmol) dissolved in dimethylformamide (5 mL) over a period of 10 minutes. Then l-fluoro-4-nitrobenzene (0.47 mL, 4.43 mmol) was added dropwise, and the resulting mixture was heated to 100 °C for 3 hours. The reaction mixture was cooled and partitioned between water (20 mL) and ethyl acetate (30 mL). The aqueous layer was further washed with ethyl acetate (2x20 mL). The organic washes were combined and dried over MgSO 4 . Solvent was removed, and the crude product was loaded onto a filter cake (70 mL silica gel -221- and 10 g anhydrous magnesium sulfate), and the product eluted with 50% acetone in hexanes (v:v). Fractions containing the desired product and the regioisomer were combined and concentrated in vacuo. The two isomers were separated by HPLC (silica gel, YMC) eluting with 10% ethyl acetate in hexanes. The regioisomers were present in a 1:2 ratio with the desired material being the minor constituent. Overall yield: 0.35 g (26%) of the desired product. MS (DCI/NH3) m/e 324 (M+H)+; !H NMR (DMSO-d6, 300 MHz) δ 8.45 (d, 2H), 7.92 (d, 2H), 7.83 (m, IH), 7.62 (s, IH), 7.05 (m, IH), 6.67 (m, IH). Example 345C (±) 4- r3-tetrahydro-2-furanyl-5-(trifluoromethyP- IH-pyrazol- 1-yllphenylamine A solution of the above compound and 10% palladium on carbon in methanol containgin one drop of concentrated hydrochloric acid was hydrogenated at 4 atm at room temperature for 18 hours, filtered through a short silica gel plug, and concentrated to provide the desire compound. MS (DCI/NΗ3) m/e 298 (M+H)+. Example 345D 3-fluoro-N-(4-(3-tetrahydro-2-furanyl-5-(trifluoromethyl)- IH-pyrazol- 1- yPphenyPisonicotinamide Example 345C was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 116-118 °C; MS (DCI/NH3) m/e 421 (M+H)+; H NMR (DMSO-d6, 300 MHz) δ 11.00 (s, IH), 8.80 (d, IH), 8.62 (dd, IH), 7.9 (d, 2H), 7.85 (t, IH), 7.52 (d, 2H), 7.10 (s, IH), 4.95-4.90 (m, IH), 3.97-3.89 (m, IH), 3.81-3.73 (m, IH), 2.30-2.21 (m, IH), 2.27-1.90 (m, 3H). Example 346 3-chloro-N-(4-(5-chloro-3-(trifluoromethyl)-lH-pyrazol-l-yI)phenyPisonicotinamide Example 325B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound using 3-chloroisonicotinic acid prepared as described in the reference below. Reference: Lecomte, L.; Ndzi, B.; Queguiner, G.; Turck, A. FR. 2,686,340-Al. mp 184-185 °C; -222- MS (DCI/NH3) m/e 418 (M + NH 4 )+; *H NMR (DMSO-d6, 300 MHz) δ 11.06 (s, IH), 8.83 (s, IH), 8.71 (d, IH), 7.92 (d, 2H), 7.73 (d, IH), 7.66 (d, 2H), 7.32 (s, IH). Example 347 N-(4-(5-chloro-3-( 1.3-thiazol-2-yP- 1 H-pyrazol- 1 -yPphenyP-3-fluoroisonicotinamide Example 347A methyl 3-oxo-3-( 1.3-thiazol-2-yl)propanoate To a cold solution (-78 °C) of diisopropylamine (7.5 mL, 51.82 mmol) in diethyl ether (200 mL) was added n-BuLi (2.5 M in hexane, 18.0 mL, 45 mmol). The resulting solution was stirred at -78 °C for 30 minutes at which point neat 2-acetylthiazole (5.07 g, 39.87 mmol) was added. The resulting solution was stirred for one hour at -78 °C and neat methyl cyanoformate (4.7 mL, 59.81 mmol) was added and the resulting mixture was stirred at -78 °C for 3 hours. The reaction mixture was then warmed to room temperature over a period of one hour. The reaction was quenched by the addition of water (150 mL). The layers were separated. The aqueous layer was acidified to pH 1, then extracted with ether (150 mL). The organic layer was dried over sodium sulfate, filtered and concentrated to give the title compound as an oil (7.37 g, 99% yield). MS (DCI NH3) m/e 186 (M + H)+; *H NMR (DMSO-d 6 , 300 MHz) δ 8.29 (d, IH), 8.18 (d, IH), 4.21 (s, 2H). Example 347B 1 -(4-nitrophenyl)-3-( 1.3-thiazol-2-vP- 1 H-pyrazol-5-ol A mixture of Example 347A (7.32 g, 39.6 mmol), 4-nitrophenylhydrazine (6.65 g, 43.5 mmol), concentrated ΗC1 (15 mL) and water (15 mL) in dioxane (200 mL) was heated at reflux for 4 hours. The reaction mixture was cooled to room temperature and approximately 75% of the solvent was removed in vacuo. The reaction mixture was diluted with brine (200 mL) and the aqueous mixture was extracted with ethyl acetate (2 x 200 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated to a crude orange solid (7.32 g, 64% yield) which was pure enough for the next step. MS (DCI/NΗ 3 ) m/e 306 (M + NH 4 )+; -223- J H NMR (DMSO-d 6 , 300 MHz) d 8.40 (d, 2H), 8.17 (d, 2H), 7.92 (d, IH), 7.79 (d, IH), 6.10 (s, IH). Example 347C 2-r5-chloro-l-(4-nitrophenyl)-lH-pyrazol-3-yl]-1.3-thiazole A mixture of the Example 347B (938 mg, 3.25 mmol) and phenylphosphinic dichloride (5.0 mL, 35.3 mmol) was heated at 150 °C for 24 hours. The reaction mixture was cooled and poured slowly into saturated sodium bicarbonate solution (150 mL). The aqueous layer was extracted with ether (3 x 150 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The crude residue was purified by flash chromatography with 90% hexane/ 10% ethyl acetate affording the title compound as a yellow oil (215 mg, 22% yield). MS (DCI/NΗ3) m/e 307 (M + H)+; ! H NMR (DMSO-d 6 , 300 MHz) δ 8.46 (d, 2H), 8.04 (d, 2H), 7.99 (d, IH), 7.86 (d, IH), 7.29 (s, IH). Example 347D 4-r5-chloro-3-(1.3-thiazol-2-yP- IH-pyrazol- 1-yllphenylamine The nitro group of Example 347C was reduced with iron as described previously. MS (DCI/NΗ3) m/e 277 (M + H)+; *H NMR (DMSO-d 6 , 300 MHz) δ 7.92 (d, IH), 7.78 (d, IH), 7.21 (d, 2H), 7.06 (s, IH), 6.68 (d, 2H), 5.58 (s, 2H). Example 347 N-(4-(5-chloro-3-( 1 ,3-thiazol-2-yP- 1 H-pyrazol- 1 -yPphenyP-3-fluoroisonicotinamide Example 347D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 194-195 °C; MS (DCI/NH3) m/e 400 (M + H)+; iH NMR (DMSO-d6, 300 MHz) δ 10.98 (s, IH), 8.79 (s, IH), 8.63 (d, IH), 7.95 (d, IH), 7.93 (d, 2H), 7.81 (d, IH), 7.75 (t, IH), 7.68 (d, 2H), 7.17 (s, IH); Anal, calcd for C 18 H,ιClFN 5 OS: C, 54.07; H, 2.77; N, 17.51. Found: C, 53.90; H, 3.05; N, 17.00. -224- Example 348 N-(4-(5-bromo-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-2.3-difluorobenzamide Example 332B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 109-112 °C; MS (DCI/NH3) m/e 446 (M+H)+; !H NMR (DMSO-d6, 300 MHz) δ 7.91 (d, 2H), 7.70-7.60 (m, IH), 7.61 (d, 2H), 7.58-7.51 (m, IH), 7.41-7.33 (m, IH), 7.30 (s, IH); Anal, calcd for C 17 H 9 F s N 3 OBr: C, 45.30; H, 2.12; N, 9.32. Found: C, 45.09; H, 2.3; N, 9.07. Example 349 N-(4-(5-bromo-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-3-chloroisonicotinamide Example 332B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 79-82 °C; MS (DCI/NH3) m e 445 (M+H)+; *H NMR (DMSO-d6, 300 MHz) δ 8.81 (s, IH), 8.70 (d, IH), 7.90 (d, 2H), 7.72 (d, IH), 7.62 (d, 2H, J=9 Hz), 7.30 (s, IH). Example 350 2-chloro-N-(4-(5-cyano-3-(trifluoromethyP- IH-pyrazol- 1-yPphenyPbenzamide Example 300D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 162-163 °C; MS (ESI) m e 391 (M+l) + , 389 (M-l) " ; !H NMR (DMSO-d6, 300 MHz) δ 10.91 (s, IH), 8.09 (s, IH), 7.98 (d, 2H), 7.79 (d, 2H), 7.67-7.46 (m, 4H); IR (KBr) cm " ' 3279, 3144, 2241, 1659, 1606, 1516, 1474, 1413, 1377, 1325, 1238, 1200, 1152,1099,972,827,751. Example 351 3-chloro-N-(4-(5-cyano-3-(trifluoromethyP- 1 H-pyrazol- 1 -yPphenyPisonicotinamide Example 300D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. -225- mp 221-222 °C; MS (ESI-) m/e 374 (M-l) ~ ; *H NMR (DMSO-d6, 300 MHz) δ 11.06 (s, IH), 8.8 (d, IH), 8.63 (dd, IH), 8.08 (s, IH), 7.97 (d, 2H), 7.82 (d, 2H), 7.76 (t, IH); IR (KBr) cm "1 3188, 3132, 3046, 2244, 1694, 1609, 1557, 1513, 1475, 1417, 1326, 1242, 1153, 1129, 1101, 972, 843. Example 352 N-(4-(5-(difluoromethoxy)-3-(trifluoromethyP- 1 H-pyrazol- 1 -yPphenyP-2-fluorobenzamide Example 322B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 130-131 °C; MS (DCI/NH3) m/e 433 (M+NH4)+; !H NMR (DMSO-d6, 300 MHz) δ 10.7 (s, IH), 7.92 (d, 2H), 7.7 (t, IH), 7.61 (d, 2H), 7.6 (m, IH), 7.32-7.41 (m, 2H), 7.15-7.65 (t, IH), 6.82 (s, IH). Example 353 2-chloro-N-(4-(5-(difluoromethoxy)-3-(trifluoromethyP-l H-pyrazol- 1-yPphenyPbenzamide Example 322B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 122-123 °C; MS (DCI/NH3) m/e 449 (M+NH4)+; 1H NMR (DMSO-d6, 300 MHz) δ 10.82 (s, IH), 7.92 (d, 2H), 7.62 (d, 2H), 7.59-7.66 (m, 2H), 7.45-7.57 (m, 2H), 7.16-7.64 (t, IH), 6.85 (s, IH). Example 354 N-(4-(5-(difluoromethoxy)-3-(trifluoromethyP- IH-pyrazol- l-yPphenyl)-2.3- difluorobenzamide Example 322B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 154-155 °C; MS (DCI/NH3) m/e 451 (M+NH4)+; l H NMR (DMSO-d6, 300 MHz) δ 10.69 (s, IH), 7.79 (d, 2H), 7.53 (d, 3H), 7.4 (t, IH), 7.2 (m, IH), 7.09-7.45 (t, IH), 6.69 (s, IH). -226- Example 355 N-(4-(5-chloro-3-(3-furyl)-lH-pyrazoI-l-yPphenyP-4-methyl-1.2.3-thiadiazole-5- carboxamide Example 355A 3-(3-furyl)-l-(4-nitrophenyl)-lH-pyrazol-5-ol Ethyl β-oxo-3-furanpropionate (2 g, 10.9 mmol) in ethanol (100 mL) was added p- nitrophenylhydrazine (1.77 g, 11.6 mmol) and 4M ΗC1 in dioxane. The mixture was heated to reflux for 3 hours. Upon cooling to room temperatur, the solvent was removed and the crude product was used in the next step without further purification. MS (APCI) m/e 270 (M-Η) " ; *Η NMR (DMSO-d6, 300 MHz) δ 8.35 (d, 2H), 8.20 (s, IH), 8.13 (d, 2H), 7.75 (t, IH), 6.88 (d, IH), 6.90 (s, IH). Example 355B 4-f5-chloro-3-(3-furyP- IH-pyrazol- 1-yllaniline Example 355A (1.0 g, 3.7 mmol) was added to phenylphosphonic dichloride (5 mL) in a sealed tube. The mixture was heated to 120 °C (oil bath) for 5 hours. Upon cooling to room temperature, the mixture was poured over a period of 30 minutes into an ice cold saturated aqueous solution of NaΗCO 3 (100 mL). The resulting mixture was extracted with ethyl acetate (3 xlOO mL). The organic layers were combined and passed through a filter cake (100 mL silica gel and 15 g annhydrous magnesium) eluting with ethyl acetate. Solvent was removed leaving the product as a brown oil. MS (DCI/NH3) m/e 260 (M+H)+ (For aniline produced under analysis conditions.) l H NMR (DMSO-d 6 , 300 MHz) δ 8.4 (d, 2H), 8.2 (s, IH), 8.0 (d, 2H), 7.8 (t, IH), 7.1 (s, IH), 6.9 (m, IH) The crude product was redissolved in ethanol/water (20 mL, 3: l/v:v). Iron powder (1.5g, 27.3 mmol) and ammonium chloride (0.206 g, 3.89 mmol) were added, and the mixture was warmed to reflux for 1 hour. After cooling to room temperature, solvent was removed, and the residue was passed through a filter cake (100 mL silica gel and 15 g annhydrous magnesium sulfate) eluting with 20% acetone in hexanes (v:v). Fractions containing the desired product were combined, and solvent was removed leaving the product as a off white solid. (0.42 g, 44% overall yield). -227- MS (DCI/NH3) m/e 260 (M+H)+; l H NMR (DMSO-d6, 300 MHz) δ 7.15 (d, 2H), 6.81 (s, IH), 6.65 (d, 2H), 5.50 (s, 2H). Example 355 N-(4-(5-chloro-3-(3-furyl)-lH-pyrazol-l-yl)phenvP-4-methyl-1.2.3-thiadiazole-5- carboxamide Example 355B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 150-152 °C; MS (DCI/NH3) m/e 386 (M+H)+; l H NMR (DMSO-d6, 300 MHz) δ 8.17 (m, IH), 7.89 (d, 2H), 7.76 (t, IH), 7.62 (d, 2H), 6.96 (s, IH), 6.86 (m, IH), 2.84 (s, 3H). Example 356 N-(4-(5-chloro-3-(3-furyl)-l H-pyrazol- l-yPphenyP-3-fluoroisonicotinamide Example 355B was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 165-166 °C; MS (DCI/NH3) m/e 383 (M+H)+; *H NMR (DMSO-d6, 300 MHz) δ 10.98 (s, IH), 8.80 (s, IH), 8.63 (d, IH), 8.18 (s, IH), 7.90 (d, 2H), 7.77-7.74 (m, 2H), 7.65 (d, 2H), 6.97 (s, IH), 6.87 (m, IH). Example 357 N-(4-(5-cyano-3-tetrahydro-2-furanyl-lH-pyrazol-l-yPphenyl)-3-fluoroisonicotinamide Example 357A (±)-N'-(4-nitrophenyl)tetrahydro-2-furancarbohydrazide A mixture of 4-nitrophenylhydrazine (719 mg, 4.70 mmol), tetrahydro-2-furoic acid (818 mg, 7.05 mmol), dimethylaminopyridine (860 mg, 7.05 mmol) and l-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.34 g, 7.05 mmol) in methylene chloride (20 mL) was stirred at room temperature for 24 hours. The reaction mixture was diluted with ethyl acetate (150 mL) and the organic mixture was washed with IN HCl solution (150 mL) and saturated sodium bicarbonate solution (150 mL). The organic layer was dried -228- over sodium sulfate, filtered and concentrated to a crude solid which was pure enough to use in the next step (1.20g, 99% yield). MS (DCI/NH3) m/e 269 (M + NH4)+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.05 (s, IH), 9.00 (s, IH), 8.06 (d, 2H), 6.71 (d, 2H), 4.43 (dd, IH), 3.95 (m, IH), 3.80 (m, IH), 2.20 (m, IH), 2.01-1.80 (m, 3H). Example 357B N-(4-nitrophenyl)tetrahydro-2-furancarbohydrazonoyl chloride A mixture of Example 357A (1.15 g, 4.58 mmol), triphenylphosphine (1.80 g, 6.87 mmol), and carbon tetrachloride (0.70 mL, 6.87 mmol) in methylene chloride (10 mL) and acetonitrile (5 mL) was stirred at room temperature for 20 hours. The reaction mixture was concentrated and purified by flash chromatography using 15% ethyl acetate/ 85% hexane to afford the title compound (420 mg, 34% yield) as an oil. MS (DCI/ΝH3) m/e 287 (M + NH4)+; J H NMR (DMSO-d 6 , 300 MHz) δ 10.45 (s, IH), 8.17 (d, 2H), 7.34 (d, 2H), 4.74 (t, IH), 3.92-3.79 (m, 2H), 2.25-1.88 (m, 4H). Example 357C l-(4-nitrophenyP-3-tetrahydro-3-furanyl-lH-pyrazole-5-carbonitrile A mixture of the Example 357C (207 mg, 0.768 mmol), 2-chloroacrylonitrile (100 mg, 1.15 mmol) and triethylamine (0.225 mL, 1.61 mmol) in toluene (5 mL) was heated to 70 °C for 2 hours. The reaction mixture was concentrated and purified by flash chromatography using 10% ethyl acetate/ 90% hexane to afford the title compound (155 mg, 71% yield) as an oil. MS (DCI/NΗ3) m/e 285 (M + H)+; ] H NMR (DMSO-d 6 , 300 MHz) δ 8.48 (d, 2H), 8.07 (d, 2H), 7.56 (s, IH), 4.99 (t, IH), 3.92 (m, IH), 3.80 (m, IH), 2.27 (m, IH), 2.00 (m, 3H). Example 357D l-(4-aminophenyl)-3-tetrahydro-3-furanyl-lH-pyrazole-5-carbonitrile The nitro group of Example 357C was reduced with iron as described previously. MS (DCI/NΗ 3 ) m/e 255 (M + H)+; ] H NMR (DMSO-d 6 , 300 MHz) δ 7.27 (d, 2H), 7.26 (s, IH), 6.67 (d, 2H), 5.57 (s, 2H), 4.91 (t, IH), 3.90 (m, IH), 3.78 (m, IH), 2.25 (m, IH), 1.98 (m, 3H). -229- Example 357 N-(4-(5-cyano-3-tetrahydro-2-furanyl-l H-pyrazol- l-yl)phenyP-3-fluoroisonicotinamide Example 357D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 160-162 °C; MS (DCI/NH 3 ) m/e 395 (M + NH 4 )+; *H NMR (DMSO-d 6 , 300 MHz) δ 11.01 (s, IH), 8.80 (s, IH), 8.62 (d, IH), 7.93 (d , 2H), 7.75 (t, IH), 7.74 (d, 2H), 7.43 (s, IH), 4.96 (t, IH), 3.93 (m, IH), 3.80 (m, IH), 2.30 (m, IH), 1.99 (m, 3H). Example 358 N-(4-(5-(difluoromethoxy)-3-(l-methyl-lH-pyrrol-3-yl)-lH-pyrazol-l-yl)phenyl)-3- fluoroisonicotinamide Example 358A methyl 3-(l -methyl- lH-pyrrol-3-yl)-3-oxopropanoate To a -78° C solution of lithium hexamethyldisilazide (2 mL, 2 mmol) in tetrahydrofuran (5 mL) was added 3 -acetyl- 1 -methy Ipyrrole (0.24 mL, 2 mmol). The reaction was warmed to 0 °C and stirred for 1 hour. The reaction mixture was again cooled to -78 °C, and methylcyanoformate (0.19 mL, 2.4 mmol) was added. After stirring for 1 hour at -78 °C, the reaction was slowly allowed to warm to room temperature. Then the reaction mixture was partitioned between ether and 1 N ΗC1. The organic layer was washed with saturated aqueous NaΗCO, and brine, dried over Na^O^ and concentrated to give crude material. Purification by ΗPLC (silica gel; acetone-hexane, 20:80) provided the desired product (0.18 g, 50% yield). MS (DCI/NΗ3) m/e 199 (M+NH4)+; !H NMR (DMSO-d6, 300 MHz) δ 7.64 (t, IH), 6.84 (dd, IH), 6.47 (dd, IH), 5.45 (s, IH), 3.67 (s, 3H), 3.66 (s, 3H). Example 358B 3-( 1 -methyl- lH-pyrrol-3-yP- 1 -(4-nitrophenyP- lH-pyrazol-5-ol Condensation of of the β-ketoester prepared above with p-nitrophenylhydrazine using conditions previously described furnished the hydroxypyrazole in 64% yield. MS (DCI/NΗ3) m/e 302 (M+NH4)+; -230- !H NMR (DMSO-d6, 300 MHz) δ 8.34 (d, 2H), 8.17 (d, 2H), 7.3 (bt, IH), 6.87 (bt, IH), 6.49 (bt, IH), 5.22 (bs, IH), 3.68 (bs, 3H). Example 358C 5-(difluoromethoxy)-3-( 1 -methyl- lH-pyrrol-3-yP- l-(4-nitrophenyl)- lH-pyrazole The difluoromethoxy ether was prepared using alkylation conditions analogous to those described in the preparation of Example 322A in 59% yield. MS (DCI/NΗ3) m/e 335 (M+H)+; 1H NMR (DMSO-d6, 300 MHz) δ 8.49 (d, 2H), 7.97 (d, 2H), 7.64-7.16 (t, IH), 7.25 (t, IH), 6.78 (t, IH), 6.48 (s, IH) 6.42 (dd, IH), 3.65 (s, 3H). Example 358D 4-r5-(difluoromethoxy)-3-(l -methyl- lH-pyrrol-3-yP- IH-pyrazol- 1-yllaniline The aniline was prepared using the iron powder reduction conditions described in the preparation of 322B in 93% yield. MS (DCI/NΗ3) m/e 305 (M+H)+; 1H NMR (DMSO-d6, 300 MHz) δ 7.51-7.03 (t, IH), 7.15 (d, 2H), 7.09 (t, IH), 6.7 (t, IH), 6.63 (d, 2H), 6.3 (dd, IH), 6.2 (s, IH), 5.33 (s, 2H), 3.63 (s, 3H). Example 358 N-(4-(5-(difluoromethoxy)-3-( 1 -methyl- lH-pyrrol-3-yP- 1 H-pyrazol- 1 -yl)phenyl)-3- fluoroisonicotinamide Example 358D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 135-136 °C; MS (DCI/NH3) m/e 428 (M+NH4) + ; 1H NMR (DMSO-d6, 300 MHz) δ 8.79 (s, IH), 8.62 (d, IH), 7.85 (d, 2H), 7.74 (t, IH), 7.62 (d, 2H), 7.17 (t, IH), 7.1-7.58 (t, IH), 6.74 (t, IH), 6.37 (dd, IH), 6.34 (s, IH), 3.65 (s, 3H). Example 359 N-(4-(5-(difluoromethoxy)-3-(3-furyP- IH-pyrazol- l-yl)phenyl)-3-fluoroisonicotinamide Example 359A -231- Example 355A (1 g, 3.89 mmol) and K,CO 3 (1.53 g, 11.1 mmol) were combined in dimethylformamide (10 mL) and heated to 50 °C. Chlorodifluoromethane was bubbled into the reaction mixture for 45 minutes. The mixture was then cooled to room temperature and partition between saturated NaCl solution (50 mL) and diethyl ether (50 mL). The organic layer was separated, the aqueous layer was washed again with diethyl ether (2 x 50 mL). The combined organic layers were dried over MgSO 4 and concentrated in vacuo. The residue was passed through a silica gel cake (150 mL) eluting with 20% acetone in hexanes and then concentrated in vacuo to provide the desired product. MS (DCI/NH3) m/e 292 (M+H) + (For the aniline produced under the analysis conditions.); iH NMR (DMSO-d6, 300 MHz) δ 8.42 (d, 2H), 8.29 (s, IH), 7.99 (d, 2H), 7.80 (t, IH), 7.42 (t, IH), 6.92 (s, IH), 6.70 (s, IH). The crude product was redissolved in 20 mL of ethanol/water (3: l/v:v). Iron powder (1.5g, 27.27 mmol) and ammonium chloride (0.206 g, 3.89 mmol) were added and the mixture was warmed to reflux for 1 hour. Upon cooling to room temperature, solvent was removed in vacuo, and the residue was loaded onto a filter cake (100 mL silica gel and 15 g anhydrous magnesium sulfate) and then eluted with 50% acetone in hexanes (v:v). Fractions containing the desired product were combined and solvent removed in vacuo leaving the product as an off white solid (0.52 g, 48% overall yield). MS (DCI/NH3) m/e 292 (M+H)+. Example 359 N-(4-(5-(difluoromethoxy)-3-(3-furyP-lH-pyrazoI-l-yPphenyl)-3-fluoroisonicotinamide Example 359 A was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound. mp 172-174 °C; MS (DCI/NH3) m/e 415 (M+H)+; H NMR (DMSO-d6, 300 MHz) δ 8.77 (m, IH), 8.60 (m, IH), 8.20 (m, IH), 7.87 (d, 2H), 7.75 (m, IH), 7.73 (m, IH), 7.63 (d, 2H), 7.35 (t, IH), 6.89 (m, IH), 6.55 (s, IH). Example 360 N-(4-(5-(difluoromethoxy)-3-(l-methyl-lH-pyrrol-2-yP-lH-pyrazol-l-yl)phenyl)-3- fluoroisonicotinamide Example 360 A -232- ethyl 3-(l-methyl-lH-pyrrol-2-yl)-3-oxopropanoate l-Methyl-2-pyrrolecarboxylic acid (1.25 g, 10 mmol) was heated to reflux in thionyl chloride (10 mL) for 2 hours. The excess thionyl chloride was removed under vacuum. Ethyl malonate (2.64 g, 20 mmol) in tetrahydrofuran (50 mL, containing 1 mg of 2,2'-bipyridyl as an indicator) was cooled to -70 °C. n-Butyllithium ( 2.5 M solution in hexane) was added slowly until the pink color persisted for several minutes. After stirring for 5 minutes, 1- methyl-2-pyrrolecarboxylic acid chloride in tetrahydrofuran (6 mL) was then added dropwise . The reaction was stirred at -70 °C for 30 minutes and slowly warmed to room temperature for 2 hours. The reaction mixture was partitioned between ether and 1 N ΗC1. The organic layer was washed with saturated aqueous NaΗCO 3 and brine, dried over Na 2 SO 4 and concentrated to give the crude beta-ketoester (0.65 g, 33% yield). MS (DCI/NH3) m/e 213 (M+NH4)+; iH NMR (DMSO-d6, 300 MHz) δ 7.2 (t, 1H), 7.11 (dd, IH), 6.15 (dd, 1H), 4.1 (q, 2H), 3.89 (s, 2H), 3.84 (s, 3H), 1.18 (t, 3H). Example 360B 3-( 1 -methyl- lH-pyrrol-2-yP- 1 -(4-nitrophenyP- lH-pyrazol-5-ol Condensation of of the beta-ketoester prepared above with p-nitrophenylhydrazine using conditions previously described furnished the hydroxypyrazole in 44% yield. MS (DCI/NΗ3) m/e 302 (M+NH4)+; *H NMR (DMSO-d6, 300 MHz) δ 8.34 (d, 2H), 8.17 (bd, 2H), 6.85 (bs, IH), 6.49 (bs, IH), 6.04 (bs, IH), 5.8 (bs, IH), 3.95 (bs, 3H). Example 360C 5-(difluoromethoxy)-3-( 1-methyl- lH-pyrrol-2-yP- 1 -(4-nitrophenyP- lH-pyrazole The difluoromethoxy ether was prepared using alkylation conditions analogous to those described in the preparation of Example 322A in 23% yield. MS (DCI/NΗ3) m/e 335 (M+H)+; *H NMR (DMSO-d6, 300 MHz) δ 8.4 (d, 2H), 8.1 (d, 2H), 7.68-7.2 (t, IH), 6.9 (t, IH), 6.63 (s, IH), 6.48 (dd, IH) 6.08 (dd, IH), 3.96 (s, 3H). Example 360D 4-r5-(difluoromethoxy)-3-(l-methyl-lH-pyrrol-2-yP-lH-pyrazoI-l-yllaniline -233- The aniline was prepared using the iron powder reduction conditions described in the preparation of 322B in quantitative yield. MS (DCI/NH3) m/e 305 (M+H)+; iH NMR (DMSO-d6, 300 MHz) δ 7.66-7.18 (t, IH), 7.2 (d, 2H), 6.8 (t, IH), 6.64 (d, 2H), 6.4 (dd, IH), 6.36 (s, IH), 6.03 (dd, IH), 5.39 (s, 2H), 3.87 (s, 3H). Example 360 N-(4-(5-(difluoromethoxy)-3-(l -methyl- lH-pyrrol-2-yl)- IH-pyrazol- l-yl)phenyP-3- fluoroisonicotinamide Example 360D was processed as in Example (i)-a (Method 5, 6, or 7) to provide the title compound, mp 154-155 °C; MS (DCI/NH3) m/e 428 (M+NH4)+; iH NMR (DMSO-d6, 300 MHz) δ 10.9 (s, IH), 8.8 (s, IH), 8.62 (d, IH), 7.87 (d, 2H), 7.74 (t, IH), 7.68 (d, 2H), 7.14-7.62 (t, IH), 6.84 (t, IH), 6.06 (t, IH), 4.49 (s, IH), 4.48 (t, IH), 3.92 (s, 3H). -234-

Claims: WHAT IS CLAIMED IS: 1. A compound having Formula I J N 3 — Q +— E I or a pharmaceutically acceptable salt or prodrug thereof, where Rl and R3 are independently selected from (1) hydrogen, (2) aryl, (3) perfluoroalkyl of one to fifteen carbons, (4) halo, (5) -CN, (6) -NO 2 , (7) -OH, (8) -OG where G is a hydroxyl protecting group, (9) -CO2R6 where R6 is selected from (a) hydrogen, (b) cycloalkyl of three to twelve carbons, (c) aryl, (d) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, (ii) alkoxy of one to fifteen carbons, (iii) thioalkoxy of one to fifteen carbons, (iv) halo, (v) -NO2, and (vi) -N 3 , (e) a carboxy protecting group, (f) alkyl of one to fifteen carbons, (g) alkyl of one to fifteen carbons substituted with 1, 2, or 3, or 4 -235- substituents independently selected from (i) alkoxy of one to fifteen carbons, (ii) thioalkoxy of one to fifteen carbons, (iii) aryl, (iv) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from alkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, -NO 2 , and -N 3 , (v) cycloalkyl of three to twelve carbons, and (vi) halo, (h) alkenyl of three to fifteen carbons, provided that a carbon of a carbon-carbon double bond is not attached directly to oxygen, (i) alkynyl of three to fifteen carbons, provided that a carbon of a carbon-carbon triple bond is not attached directly to oxygen, and (j) cycloalkyl of three to twelve carbons, (10) -LiNRγRg where Li is selected from (a) a covalent bond, (b) -X'C(X)- where X and X' are independently O or S, (c) -C(X)-, and (d) -NR 6 - and R 7 and R% are independently selected from (a) hydrogen, (b) alkanoyl where the alkyl part is one to fifteen carbons, (c) alkoxycarbonyl where the alkyl part is one to fifteen carbons, (d) alkoxycarbonyl where the alkyl part is one to fifteen carbons and is substituted with 1 or 2 substituents selected from the group consisting of aryl, (e) cycloalkyl of three to twelve carbons, -236- (g) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, (ϋ) alkoxy of one to fifteen carbons, (ϋi) thioalkoxy of one to fifteen carbons, (iv) halo, (v) -NO 2 , and (vi) -N 3 , (h) -OR 6 , provided that only one of R or Rg is -OR6, (i) a nitrogen protecting group, (j) alkyl of one to fifteen carbons, (k) alkyl of one to fifteen carbons substituted with 1, 2, or 3, or 4 substituents independently selected from (i) alkoxy of one to fifteen carbons, (ϋ) thioalkoxy of one to fifteen carbons, (ϋi) aryl, (iv) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from alkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, -NO2, and -N 3 , (v) cycloalkyl of three to fifteen carbons, (vi) halo, (vii) -CO 2 R6, and (viii) -OH, (1) alkenyl of three to fifteen carbons, provided that a carbon of a carbon-carbon double bond is not attached directly to nitrogen, (m) alkynyl of three to fifteen carbons, -237- provided that a carbon of a carbon-carbon triple bond is not attached directly to nitrogen, 100 (n) -SO 2 -alkyl, and (o) cycloalkyl of three to twelve carbons, or R and Rs together with the nitrogen atom to which they are attached form a ring selected from (i) aziridine, 105 (ii) azetidine, (iii) pyrrolidine, (iv) piperidine, (v) piperazine, (vi) morpholine, 110 (vii) thiomorpholine, and (viii) thiomorpholine sulfone where (i)-(viii) can be optionally substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl of one to fifteen carbons, 115 (11) -L2R9 where L 2 is selected from (a) -Li-, (b) -O-, and (c) -S(O) t - where t is 0, 1 , or 2 and R9 is selected from 120 (a) cycloalkyl of three to twelve carbons, (b) aryl (c) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, 125 (ii) alkoxy of one to fifteen carbons, (iii) thioalkoxy of one to fifteen carbons, (iv) halo, (v) -NO2, and (vi) -N 3 , 130 (d) alkyl of one to fifteen carbons, (e) heterocycle, -238- (f) alkenyl of two to fifteen carbons, and (e) alkyl of one to fifteen carbons substituted with 1, 2, or 3, or 4 substituents independently selected from 135 (i) alkenyl of two to fifteen carbons, (ii) alkoxy of one to fifteen carbons, (iii) -CN, (iv) -CO 2 R 6 , (v) -OH, 140 provided that no two -OH groups are attached to the same carbon, (vi) thioalkoxy of one to fifteen carbons, (vii) alkynyl of two to fifteen carbons, (viii) aryl, 145 (ix) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from alkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, 150 halo, -NO2, and -N 3 , (x) cycloalkyl of three to twelve carbons, and (xi) halo, 155 (xii) -NR 7 R 8 , (xiii) heterocycle, and (xiv) heterocycle substituted with 1, 2, or 3, or 4 substituents independently selected from alkyl of one to fifteen carbons, 160 alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, -NO 2 , and -N3, 165 (12) alkyl of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 halo substituents, -239- (13) alkyl of one to fifteen carbons, (14) alkenyl of two to fifteen carbons, (15) alkynyl of two to fifteen carbons where (13)-(15) can be optionally substituted with 170 (a) (=X), (b) alkanoyloxy where the alkyl part is one to fifteen carbons, (c) alkoxy of one to fifteen carbons, (d) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo, 175 (e) thioalkoxy of one to fifteen carbons, (f) perfluoroalkoxy of one to fifteen carbons, (g) -N 3 , (h) -NO 2 , (i) -CN, 180 0) -OH, (k) -OG (1) cycloalkyl of three to twelve carbons, (m) halo, (n) -CO 2 R 6 , 185 (o) -LιNR 7 R 8 , and (p) -L2R9, (16) -L2-heterocycle, and (17) -L2-heterocycle where the heterocycle is substituted with 1, 2, 3 or 4 substituents independently selected from 190 (a) alkyl of one to fifteen carbons, (b) perfluoroalkyl of one to fifteen carbons, (c) alkoxy of one to fifteen carbons, (d) thioalkoxy of one to fifteen carbons, (e) halo, and 195 (f) -NO 2 , (18) -NRχC(O)NRγRz where Rχ ? Ry and Rz are independently selected from (a) hydrogen and (b) alkyl of one to fifteen carbons, (19) -C(=NRχ)NRγR z , -240- 200 (20) -NRχC(=NRχ')NRγRz where Rx, Ry and Rz are defined previously and Rx is selected from (a) hydrogen and (b) alkyl of one to fifteen carbons, (21 ) -NRχC(O)OR , where R w is selected from 205 (a) alkyl of one to fifteen carbons and (b) alkenyl of three to fifteen carbons, provided that a carbon of a carbon-carbon double bond is not attached directly to oxygen, and (22) -OC(O)NR 7 R 8 ; 210 Z is nitrogen or carbon; R. 2 is absent or is selected from (1) hydrogen, 215 (2) -CO 2 R 6 , (3) alkyl of one to fifteen carbons, (4) -C(O)R6' where RQ is selected from (a) alkyl of one to fifteen carbons, (b) aryl, and 220 (c) heterocycle, (5) -C(O)NR 7 'R8' where R 7 ' and R% are independently selected from (a) hydrogen, (b) alkyl of one to fifteen carbons, or R 7 ' and R together with the nitrogen to which they are attached form a ring 225 selected from (i) piperidine, (ii) piperazine, (iii) morpholine, (iv) thiomorpholine, and 230 (v) thiomorpholine sulfone (6) perfluoroalkyl of one to fifteen carbons, (7) cycloalkyl of three to ten carbons, (8) alkyl of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents -241- selected from the group conststing of halo, 235 (9) alkyl of one to fifteen carbons substituted with (a) -CN, (b) -OH, provided that no two -OH groups are attached to the same carbon, (c) (=X), and 240 ( ) -CO R6, and (10) halog( in; provided that when X is nitrogen, R 2 is absent; Q is aryl or heterocycle where, when Q is phenyl, the phenyl is 2-, 3-, or 4- substituted 245 by E relative to the position of attachment of the pyrazole or 1,2,4-triazole ring to the phenyl ring; R 4 and R5 are independently selected from (I) hydrogen, 250 (2) alkyl of one to fifteen carbons, (3) alkyl of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 halo substituents, (4) alkyl of one to fifteen carbons substituted with (a) -CN, (b) -CO 2 R 6 , 255 (c) -L 1 NR7R8, and (d) -L 2 R 9 , (5) perfluoroalkyl of one to fifteen carbons, (6) -CN, (7) -CO 2 R 6 , 260 (8) -L ! NR 7 R 8 , (9) -L2R9, (10) alkoxy of one to fifteen carbons, (I I) thioalkoxy of one to fifteen carbons, (12) halo, 265 (13) -C(=NR 6 )NR 7 R 8 , (14) -NRι 2 (=NR6)NR 7 R8 where R6, R7, and Rs are defined previously and Rι is selected from -242- (a) hydrogen, (b) cycloalkyl of three to twelve carbons, 270 (c) aryl, (d) alkyl of one to fifteen carbons, and (e) alkyl of one to fifteen carbons substituted with 1, 2, or 3, or 4 substituents independently selected from (i) alkenyl of two to fifteen carbons, 275 (ii) alkoxy of one to fifteen carbons, (iii) thioalkoxy of one to fifteen carbons, (iv) alkynyl of two to fifteen carbons, and (v) aryl, (15) -L 2 -heterocycle, and 280 (16) -L2-heterocycle where the heterocycle is substituted with 1, 2, 3, or 4 substituents independently selected from (a) alkyl of one to fifteen carbons, (b) perfluoroalkyl of one to fifteen carbons, (c) alkoxy of one to fifteen carbons, 285 (d) thioalkoxy of one to fifteen carbons, (e) halo, (f) -N 3 , and (g) -NO 2 ; 290 E is (1) -L3-B where L3 is selected from (a) a covalent bond, (b) alkenylene of two to six carbons in the Z or E configuration, (c) alkynylene of two to six carbons, 295 (d) -C(X)-, (e) -N=N-, ω -NR7-, (g) -N(R 7 )C(O)N(R 8 )-, (h) -N(R 7 )SO 2 N(R 8 )-, 300 (i) -X-, 0 ) -(CH 2 ) m O-, -243- (k) -O(CH 2 ) m -, (1) -N(R 7 )C(X)-, (m) -C(X)N(R 7 )-, 305 (n) -S(O) t (CH 2 ) m -, (o) -(CH 2 ) m S(O) r , (p) -NR 7 (CH 2 ) m -, (q) -(CH 2 ) m NR 7 -, (r) -NR 7 S(O) r , 310 (s) -S(O) t NR 7 -, (t) -N=C(H)-, (u) -C(H)=N-, (v) -ON=CH-, (w) -CH=NO- 315 where (g)-(w) are drawn with their left ends attached to Q, (x) -N(R 7 )C(O)N(Rιo)(Rι ι)- where Rio and Ri i together with the nitrogen atom to which they are attached form a ring selected from (i) morpholine, (ii) thiomorpholine, 320 (iii) thiomorpholine sulfone, and (iv) piperidine where (i)-(iv) are attached to Q through the nitrogen to which is attached R7 and to B through a carbon in the ring, (y) -N(R 7 )SO 2 N(Rιo)(Rι ι)-, and 325 (z) -N(R 7 )C(O)N(Rιo)(Rn)- and B is selected from (a) alkyl of one to fifteen carbons, (b) alkenyl of three to fifteen carbons in the E or Z configuration, provided that a carbon of a carbon-carbon double bond is not directly 330 attached to L3 when L 3 is other than a covalent bond, (c) alkynyl of three to fifteen carbons, provided that a carbon of a carbon-carbon triple bond is not directly attached to L 3 when L 3 is other than a covalent bond where (a), (b) and (c), can be optionally substituted with 1, 2, 3, or 4 335 substituents independently selected from -244- RB RA ^^^ RC (i) R E where L 2 is defined previously and RA, RB. Rc, RD > and RE are independently selected from hydrogen, alkanoyl where the alkyl part is one to fifteen carbons, 340 alkanoyloxy where the alkyl part is one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, alkoxy of one to fifteen carbons substituted with 1, 2, 3, 345 4, or 5 substituents selected from the group consisting of halo , perfluoroalkyl of one to fifteen carbons, perfluoroalkoxy of one to fifteen carbons, -N 3 , 350 -NO2, -CN, -OH, -OG, cycloalkyl of three to fifteen carbons, 355 halo, -CO 2 R 6 -LιNR 7 R 8 -L 2 R 9 alkyl of one to fifteen carbons, 360 alkyl of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents independently selected from (=X), alkanoyloxy where the alkyl part is one to fifteen carbons, 365 alkoxy of one to fifteen carbons, -245- thioalkoxy of one to fifteen carbons, alkoxy of one to fifteen carbons substituted with 1, 2, 3,4, or 5 halo substituents, perfluoroalkoxy of one to fifteen carbons, 370 -N 3 , -NO 2 , -CN, -OH, provided that no two -OH groups are attached to 375 the same carbon, -OG, cycloalkyl of three to fifteen carbons, halo, -CO 2 R 6 , 380 -LιNR 7 R 8 , and - 2 R 9 , -L2-heterocycle, and -L2-heterocycle where the heterocycle is substituted with 385 1, 2, 3, or 4 substituents independently selected from alkyl of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, 390 thioalkoxy of one to fifteen carbons, halo, -NRχC(O)NR γ R z , -C(=NRX)RγR z , -NO 2 , and 395 -N 3 , (ϋ) (=X) (iii) alkanoyloxy where the alkyl part is one to fifteen carbons, (iv) alkoxy of one to fifteen carbons, (v) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 -246- 400 substituents selected from the group consisting of halo, (vi) thioalkoxy of one to fifteen carbons, (vii) perfluoroalkoxy of one to fifteen carbons, (viii) -N3, (ix) -NO 2 , 405 (x) -CN, (xi) -OH, provided that no two -OH groups are attached to the same carbon, (xii) -OG, 410 (xiii) cycloalkyl of three to fifteen carbons, (xiv) halo, (xv) -CO 2 R 6 , (xvi) -LιNR 7 R 8 , (xvii) perfluoroalkyl of one to fifteen carbons, 415 (xviii) -L 2 -heterocycle, and (xix) -L 2 -heterocycle where the heterocycle is substituted with 1 , 2, 3, or 4 substituents independently selected from (=X), alkanoyl where the alkyl part is one to fifteen carbons, 420 alkanoyloxy where the alkyl part is one to fifteen carbons, alkoxy of one to fifteen carbons, alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group 425 consisting of halo , thioalkoxy of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, perfluoroalkoxy of one to fifteen carbons, -N 3 , 430 -NO2, -CN, -OH, provided that no two -OH groups are attached to the -247- same carbon, 435 -OG, cycloalkyl of three to fifteen carbons, halo, -CO 2 R 6 , -LιNR 7 R 8 , and 440 -L2R9, (d) cycloalkyl of three to twelve carbons, (e) cycloalkenyl of four to twelve carbons, provided that a carbon of a carbon-carbon-double bond is not attached directly to L 3 when L 3 is other than a covalent bond 445 where (d) and (e) can be optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, (ϋ) aryl, (iii) alkoxy of one to fifteen carbons, 450 (iv) thioalkoxy of one to fifteen carbons, (v) halo, (vi) -OH, provided that no two -OH groups are attached to the same carbon, 455 (vii) oxo, (viii) perfluoroalkyl, (ix) heterocycle, and (x) heterocycle substituted with 1, 2, 3, 4, or 5 substituents independently selected from 460 alkyl of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, 465 -NO 2 , and -N 3 , -248- R, R A\^ R^c (f) R E provided that when Ri and R 3 are both perfluoroalkyl of one carbon, Z is carbon, R 2 is hydrogen, Q is phenyl that is 4-substituted by E 470 relative to the position of attachment of the pyrazole ring to the phenyl group, R4 and R5 are hydrogen, E is -L 3 -B, L 3 is -N(R 7 )C(X)-, R 7 is hydrogen, X is oxygen, and RA, RB, RD > and Rβ are hydrogen, Re is other than chloro, and (g) heterocycle where the heterocycle can be optionally substituted with 1 , 475 2, 3, or 4 substituents independently selected from (i) (=X), (ii) alkanoyl where the alkyl part is one to fifteen carbons, (iii) alkanoyloxy where the alkyl part is one to fifteen carbons, 480 (iv) alkoxy of one to fifteen carbons, (v) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo, (vi) halo , 485 (vii) thioalkoxy of one to fifteen carbons, (viii) perfluoroalkyl of one to fifteen carbons, (ix) perfluoroalkoxy of one to fifteen carbons, (x) -N 3 , (xi) -NO2, 490 (xii) -CN, (xiii) -OH, provided that no two -OH groups are attached to the same carbon, (xiv) -OG, 495 (xv) cycloalkyl of three to fifteen carbons, (xvi) halo, -249- (xvii) -CO 2 R 6 , (xviii) alkyl optionally substituted with -OH, (xix) -L 1 NR 7 R 8 , and 500 (xx) -L 2 R 9 , provided that when Ri and R 3 are perfluoroalkyl of one carbon, Z is carbon, R 2 is hydrogen, Q is phenyl that is 4- substituted by E relative to the position of attachment of the pyrazole ring to the phenyl group, R 4 and R5 are 505 hydrogen, E is -L 3 -B, L 3 is -N(R 7 )C(X)-, R 7 is hydrogen, X is oxygen, and B is a 1,2,3-thiadiazolyl ring attached to L 3 through the 5-position of the ring, the substituent at the 4-position of the 1,2,3-thiadiazolyl ring is other than alkyl of one carbon, and 510 further provided that when Ri and R 3 are perfluoroalkyl of one carbon, Z is carbon, R 2 is hydrogen, Q is phenyl that is 4-substituted by E relative to the position of attachment of the pyrazole ring to the phenyl group, R4 and R5 are hydrogen, E is -L3-B, L 3 is -N(R 7 )C(X)-, R is 515 hydrogen, X is oxygen, and B is an isoxazole ring attached to L3 through the 4-position of the ring, the substituents at the 3- and 5- positions of the isoxazole ring are not both alkyl of one carbon or % -R13 520 (2) where Rι 3 and R14 are independently selected from (a) hydrogen, (b) alkyl of one to fifteen carbons, (c) alkenyl of three to fifteen carbons in the E or Z configuration, provided that a carbon of a carbon-carbon double bond is not attached 525 directly to the C(=O) group, (d) alkynyl of three to fifteen carbons, provided that a a carbon-carbon triple bond is not directly attached to -250- the C(=O) group where (b), (c), and (d) can be optionally substituted with 1, 2, 3, or 4 530 substituents independently selected from RB R A\ RC (i) RE (ϋ) (=X), (iii) alkanoyloxy where the alkyl part is one to fifteen carbons, (iv) alkoxy of one to fifteen carbons, 535 (v) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo, (vi) thioalkoxy of one to fifteen carbons, (vii) perfluoroalkoxy of one to fifteen carbons, (viii) -N 3 , 540 (ix) -NO2, (x) -CN, (xi) -OH, provided that no two -OH groups are attached to the same carbon, (xii) -OG, 545 (xiii) cycloalkyl of three to fifteen carbons, (xiv) halo, (xv) -CO 2 R 6 , (xvi) -L!NR 7 R 8 , (xvii) perfluoroalkyl of one to fifteen carbons, 550 (xviii) -L2-heterocycle, and (xix) -L2-heterocycle where the heterocycle is substituted with 1, 2, 3, or 4 substituents independently selected from (=X), alkanoyl where the alkyl part is one to fifteen carbons, 555 alkanoyloxy where the alkyl part is one to fifteen carbons, alkoxy of one to fifteen carbons, alkoxy of one to fifteen carbons substituted with 1, 2, 3, -251- 4, or 5 substituents selected from the group 560 consisting of halo, thioalkoxy of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, perfluoroalkoxy of one to fifteen carbons, -N 3 , 565 -NO 2 , -CN, -OH, provided that no two -OH groups are attached to the same carbon, 570 -OG, cycloalkyl of three to fifteen carbons, halo, -CO 2 R6, -LιNR 7 R 8 , 575 -L2R9, (e) cycloalkyl of three to twelve carbons, (f) cycloalkenyl of four to twelve carbons, provided that a carbon of a carbon-carbon double bond is not attached directly to the C(=O) group 580 where (e) and (f) can be optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, (ii) aryl, (iii) alkoxy of one to fifteen carbons, 585 (iv) thioalkoxy of one to fifteen carbons, (v) halo, (vi) -OH, provided that no two -OH groups are attached to the same carbon, 590 (vii) heterocycle, and (viii) heterocycle substituted with 1, 2, 3, 4, or 5 substituents independently selected from -252- alkyl of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, 595 alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, -NO2, and -N 3 , 600 (g) heterocycle, and (h) heterocycle substituted with 1, 2, 3, or 4 substituents independently selected from (i) (=X), (ii) alkanoyl where the alkyl part is one to fifteen carbons, 605 (iii) alkanoyloxy where the alkyl part is one to fifteen carbons, (iv) alkoxy of one to fifteen carbons, (v) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group 610 consisting of halo, (vi) thioalkoxy of one to fifteen carbons, (vii) perfluoroalkyl of one to fifteen carbons, (viii) perfluoroalkoxy of one to fifteen carbons, (ix) -N 3 , 615 (x) -NO2, (xi) -CN, (xii) -OH, provided that no two -OH groups are attached to the same carbon, 620 (xiii) -OG, (xiv) cycloalkyl of three to fifteen carbons, (xv) halo, (xvi) -CO 2 R 6 , (xvii) -LιNR 7 R 8 , 625 (xviii) -L2R9, provided that at least one of R 1 3 and R14 is other than hydrogen, or -253- R l3 and R 14 together with the nitrogen to which they are attached form a ring selected from (a) succinimidyl, 630 (b) maleimidyl, (c) glutarimidyl, (d) phthalimidyl, (e) naphthalimidyl, H 3 C V Jl (f) V o o H 3 C N I H,C N y 635 (g) O o H a 3C°S A H C (h) O O & H 3 C (i) (j) (k) 640 (1) , and -254- O I A. (m) CH where (a)-(m) can be optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo and 645 -L2R9. 2. A compound according to Claim 1 of Formula R 2 ; R 3 R4 N z^\ r-\= J- N_ \\ ) ~E R * , or a pharmaceutically acceptable salt or prodrug thereof, where 5 Z is carbon, R 2 is hydrogen, and R R 3 , R 4 , R 5 , and E are defined above. 3. A compound according to Claim 2 where Ri is perfluoroalkyl of one to fifteen carbons and R4 and R5 are hydrogen. 4. A compound according to Claim 3 where L3 is -N(R 7 )C(X)-, R 7 is hydrogen, and W is O. 5. A compound according to Claim 4 selected from N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-cyclopropanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,2,3,3- tetramethylcyclopropanecarboxamide, 5 N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-2,2-dichloro- 1 - methylcyclopropanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-oxo-6-pentyl-2H-pyran-3- carboxamide, -255- N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]- 1 -cyclohexene- 1- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2- methylcyclopropanecarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] -5-(3 , 5-dichlorophenoxy)-2- f urancarboxamide , N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl] - 1 -methyl-2-cyclohexene- 1 - carboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] - 1 -cyclopentene- 1 - carboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] -3- methoxycyclohexanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-butynamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenylJ-2-methyl-3-nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yljphenyl]- 1 - hydroxycyclopropanecarboxamide, N-[4[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyljcycloheptanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-benzofurancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-fluoro-lH-indole-2- carboxamide, (E)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-(2-chlorophenyl)-2- propenamide, 2-benzoyl-N-[4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyljbenzamide , 3a(S)-(3aα,4β,6aα)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-ylJ- pheny 1] hexahydro-2-oxo- 1 H-thieno [3 ,4-d] imidazole-4-pentanamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-iodobenzamide, exo-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-ylJphenyl]bicyclo[2.2.1]hept-5-ene- 2-carboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-2-methylcyclo- hexanecarboxamide, (R)-phenylmethyl [ 1 - [[[4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 - yljphenyl] amino] carbonyljpropyljcarbamate, -256- N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-cyclohexene-l- carboxamide, N- [4-[3,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl]- 1 -methylcyclopropane- carboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl] -5-methyl-2-thiophene- carboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]-4-(lH-pyrrol-l-yl)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-7-methoxy-2-benzofuran- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-(hydroxymethyl)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-cyanoacetamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-cyclohexane-l- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-methylcyclohexane- carboxamide, (R)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-α-methoxy-α- (trifluoromethyl)benzeneacetamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]heptanamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-phenoxybenzamide, 3-Amino-N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]benzamide, 4-Amino-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, 4-Azido-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-2-thiopheneacetamide, N-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l-tricyclo[3.3.1.1 3 ' 7 ]- decanecarboxmide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-N 2 - [( 1 , 1 -dimethylethoxy )- carbonyl]-L-asparagine, phenylmethyl ester, 1 , 1 -dimethylethyl [7-[[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]amino]- N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-(methylthio)propanamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l-naphthylenecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-cyanobenzamide, (trans)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-phenyl- cyclopropanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-iodobenzamide, -257- N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-3-chloropropanamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-4-methoxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2-ethylhexanamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-4-hydroxybenzamide, 80 N-[4-[3,5-bis(trifluoromethyl)- lH-pyrazol- -yl]phenyl]-4-(hexyloxy)benzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]pheny 1] -3 -methylbenzamide , 2-(acetyloxy)-N-[4-[3,5-bis(trifluoromethyl -IH-pyrazol- 1 -yl]phenyl]benzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2,4,6-trimethylbenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]- 1 -methyl-5-nitro- 1 H- 85 pyrazole-4-carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-4-bromobenzamide' N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2-(dimethylamino)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-3-(dimethylamino)benzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-4-(trifluoromethyl)benzamide, 90 N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-4-fluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2-chlorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl] phenyl] -4-nitrobenzamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2-methylbenzamide, 95 N-[4-[3,5-bis(trifluoromethyl)- lH-pyrazol- -yl]phenyl]-3,4-dimethoxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]cyclopentanepropanamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl] phenyl] -4-methy lbenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-3-(trifluoromethyl)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-3-methyl-2-butenamide, 100 N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2-hydroxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl] phenyl] -3 -hy droxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2,4-dimethyl-5-thiazole- carboxamide, N-[4-[3,5-bis(trifluoromethyP- lH-pyrazol- -yl]phenyl]-3-pyridinecarboxamide, 105 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-4-(hydroxymethyl)benzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-4-(methylsulfonyl)benzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2-iodobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-4-heptybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2-furancarboxamide, -258- 110 N-[4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-2-fluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-N'-methyl- 1 ,2-benzene- dicarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-4-pyridinecarboxamide, N- [4- [3, 5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-4-chloro-2-nitrobenzamide, 115 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-cinnolinecarboxamide, 4-acetyl-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, 1,1-dimethylethyl 4-[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]- amino]carbonyl]- 1 -piperidinecarboxylate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-pyridinecarboxamide, 120 N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]-4-(diethylamino)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]cyclopentanecarboxmide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]cyclohexanecarboxmide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-piperidinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-(methylsulfonyl)benzamide, 125 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-(trifluoromethyl)benzamide, methyl 3-[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]amino]- carbonyl]benzoate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-chlorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-2-thiophenecarboxamide, 130 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l,4-benzenedicarboxamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3,5-dinitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,4-difluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-nitrobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl] -3-cyanobenzamide, 135 N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yljphenyl]- 1 ,3-benzenedicarboxamide , N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-3-nitrobenzamide, 3-(aminosulfonyl)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, methyl 4-[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]amino]- carbonyl]benzoate, 140 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-methoxybenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-bromobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-methoxybenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-fluorobenzamide, -259- N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl] -2-bromobenzamide, 145 N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]-l, 3-benzodioxole-5- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,6-dichloro-3- pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-chloro-3- 150 pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-chloro-6-methyl-3-, pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-fluoro-γ- oxobenzenebutanamide, 155 N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] - 1 ,2,3 ,4-tetrahydro-2- naphthalenecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-(4-chlorophenoxy)-2- methylpropanamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yljphenyl] acetamide, 160 4- [ [ [4- [3 ,5 -bis(trifluoromethyl) - 1 H-pyrazol- 1 -yljphenyl] amino] carbonyl]benzoic acid, phenylmethyl N- [4- [3, 5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]amino]-4- oxobutyl]carbamate, 3-[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]amino]carbonyl]benzoic acid, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-bromo-2-thiophene- 165 carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-methyl-2-thiophene- carboxamide, 2-amino-N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-fluoro-3-pyridine- 170 carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-chloro-4-(methylsulfonyl)- 2-thiophenecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-lH-pyrrole-2-carboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-3 ,6-dichloro-2-pyridine- 175 carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-(2-nitrophenoxy)acetamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]- 1 H-indole-2-acetamide, -260- (E)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-(2-thienyl)-2- propenamide, N- [4- [3,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]py azinecarboxamide, 1 , 1 -dimethylethyl [[4-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yljphenyl] amino] - 4-oxobutyl]carbamate, 1 -acetyl-N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-4-piperidine- carboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazo -yl]phenyl butanamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol -yljphenyl -4-chloro-2- methoxybenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazo^ -yljphenyl -α-methyl-4-(2- thienylcarbonyl)benzeneacetamide, N-[4-[3,5-bis(trifluoromethyl)- lH-pyrazo -yljphenyl -α-methyl-4-(2- thienylcarbonyl)benzeneacetamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazo -yljphenyl -2-methoxy-4- (methythio)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazo -yljphenyl -4-hydroxy-3-nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazo -yljphenyl -3 ,4-dihydroxybenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazo -yljphenyl -2-hydroxy-6- methoxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazo -yljphenyl -2,4- bis(trifluoromethyl)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazo -yljphenyl -5-methyl-4- isoxazolecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazo: -yl]phenyl -4-fluoro-3- (trifluoromethyl)benzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol -yl]phenyl -4-fluoro-3-nitrobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazo -yljphenyl -4-fluoro-2- (trifluoromethyl)benzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazo -yljphenyl -2-bromo-3 -nitrobenzamide , N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazo -yl]phenyl -2-chloro-4-fluorobenzamide, N- [4- [3, 5-bis(trifluoromethyl)- IH-pyrazol -yljphenyl -2-chloro-4-(methylsulfonyl)- benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,5-dichlorobenzamide, -261- N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,3-difluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3-chloro-4-fluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,5-difluorobenzamide, 215 N- [4- [3 , 5 -bis(trifluoromethy 1)- H-pyrazol- -yl]phenyl]-2-chloro-6-fluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyP- H-pyrazol- -ylJphenyl]-2-fluoro-6-(trifluoromethyl)- benzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -ylJphenyl]-3-chloro-2-fluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2-chloro-4- 220 methoxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,6-dichloro-3- nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-bromo-2-chlorobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3,4-difluorobenzamide, 225 N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2-bromo-5- methoxybenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-4-chloro-2- hydroxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenylJ-3-bromo-4- 230 methoxybenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3-bromo-4- hydroxybenzamide, N- [4- [3 , 5 -bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2-chloro-4,5- difluorobenzamide, 235 N-[4-[3,5-bis(trifluoromethyP- H-pyrazol- -yl]phenylJ-4-chloro-2,5- difluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,3,4-trifluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-3,4,5-trifluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,4,5-trifluorobenzamide, 240 N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,4,6-trifluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -y 1] phenyl] -2 ,6-difluoro-3 - nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,3,5-trifluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- H-pyrazol- -yl]phenyl]-2,4-dichloro-6- 245 fluorobenzamide, -262- N-4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl-2,4-dichloro-3 ,5- dinitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,3,5,6-tetrafluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,3,4,5-tetrafluorobenzamide, 250 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-bromo-2,3,5,6-tetrafluoro- benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-methyl-2-nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-thiophene-carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-isoxazolecarboxamide, 255 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]tetrahydro-2- furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-pyrrolidinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]tetrahydro-3- furancarboxamide, 260 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l,2,3-thiadiazole-5- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-chloro-4-pyridine- carboxamide, 1,1-dimethylethyl 2-[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]- 265 amino]carbonyl]- 1-pyrrolidinecarboxylate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-nitro-2-furancarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl]- 1 -methyl- 1 H-pyrrole-2- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-6-chloro-3-pyridine- 270 carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-bromo-2-furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-methyl-2- furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-chloro-2-thiophene- 275 carboxamide, (S)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]tetrahydro-5-oxo-2- furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-oxo-2-pyrrolidine- carboxamide, -263- N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-bromo-3- pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-nitro-3-thiophene- carboxamide, 1 , 1 -dimethylethyl 4-[[[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]- amino]carbonyl]-3-thiazolidinecarboxylate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-methoxy-3-thiophene- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,3-dibromo-5-thiophene- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-fluoro-4-pyridine- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l-methyl-lH-pyrazole-4- carboxamide, N- [4- [3, 5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-5-chloro-4-methoxy-3- thiophenecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5,6-dichloro-3-pyridine- carboxamide, N-[4-[3,5-bis(trifluorornethyl)- IH-pyrazol- 1 -yl]phenyl]-2,6-dichloro-4-pyridine- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,5-dichloro-3-pyridine- carboxamide, 3-amino-N-(4-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)isonicotinamide, N-(4-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-3-chloro-5- methoxyisonicotinamide, 4-(aminomethyl)-N-(4-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2- chlorobenzamide, N-(4-(3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-2-methylacrylamide, N-(4-(3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-4-chloro-2-fluorobenzamide, N-(4-(5-cyano-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-2-fluorobenzamide, 2-fluoro-N-(4-(5-(2-furyl)-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)benzamide, N-(4-(5-cyano-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-4-methyl- 1 ,2,3- thiadiazole-5-carboxamide, N-(4-(5-cyano-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)isonicotinamide, -264- N-(4-(5-cyano-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-3-fluoroisonicotinamide, 315 N-(4-(5-acetyl-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-2-fluorobenzamide, N-(4-(5-cyano-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-2-fluoronicotinamide, N-(4-(5-cyano-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2,3,5-trifluorobenzamide, 2-fluoro-N-(4-(5-(2-thienyl)-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)benzamide, 2-fluoro-N-(4-(5-(methylsulfanyl)-3-(trifluoromethyl)-lH-pyrazol-l- 320 yl)phenyl)benzamide, 2-fluoro-N-(4-(5-(3-pyridinyl)-3-(trifluoromethyl)- IH-pyrazol- 1- yPphenyPbenzamide, 3-fluoro-N-(4-(5-(2-thienyl)-3-(trifluoromethyl)-lH-pyrazol-l- yl)phenyl)isonicotinamide, 325 N-(4-(5-methoxy-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)isonicotinamide, 2-fluoro-N-(4-(5-methoxy-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)benzamide, N-(4-(5-methoxy-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-4-methyl- 1,2,3- thiadiazole-5-carboxamide, N-(4-(5-acetyl-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2-fluoronicotinamide, 330 2-fluoro-N-(4-(5-(methylsulfanyl)-3-(trifluoromethyl)- IH-pyrazol- 1 - yPphenyPnicotinamide, 2-fluoro-N-(4-(5-methoxy-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)nicotinamide, N-(4-(5-ethoxy-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-2-fluoronicotinamide, 3-fluoro-N-(4-(5-(methylsulfanyl)-3-(trifluoromethyl)- 1 H-pyrazol- 1 - 335 yPphenyPisonicotinamide, 3-fluoro-N-(4-(5-methoxy-3-(trifluoromethyl)- 1 H-pyrazol- 1 - yl)phenyl)isonicotinamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- 1 H-pyrazol- 1 - yPphenyPisonicotinamide, 340 N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-4-methyl- 1 ,2,3-thiadiazole-5-carboxamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2- fluoronicotinamide, N-(4-(5-chloro-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-2-fluoronicotinamide, 345 2-fluoro-N-(4-(5-nitro-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)benzamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- IH-pyrazol- l-yl)phenyl)-3- fluoroisonicotinamide, -265- N-(4-(5-chloro-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-3-fluoroisonicotinamide, N-(4-(5-bromo-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-3-fluoroisonicotinamide, 350 3-fluoro-N-(4-(5-nitro-3-(trifluoromethyl)-l H-pyrazol- 1 -yPphenyPisonicotinamide, N-(4-(5-bromo-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-4-methyl- 1 ,2,3-thiadiazole- 5-carboxamide, N-(4-(5-chloro-3-(trifluoromethyl)- IH- 1 ,2,4-triazol- 1 -yl)phenyl)-3- fluoroisonicotinamide, 355 3-fluoro-N-(4-(5-(l -methyl- lH-pyrrol-3-yl)-3-(trifluoromethyP- IH-pyrazol- 1- yPphenyPisonicotinamide, 3-chloro-N-(4-(5-chloro-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyPisonicotinamide, N-(4-(5-bromo-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2,3-difluorobenzamide, N-(4-(5-bromo-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-3-chloroisonicotinamide, 360 2-chloro-N-(4-(5-cyano-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)benzamide, 3-chloro-N-(4-(5-cyano-3-(trifluoromethyl)- IH-pyrazol- 1 -yPphenyPisonicotinamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-2- fluorobenzamide, 2-chloro-N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- IH-pyrazol- 1- 365 yPphenyPbenzamide, and N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2,3- difluorobenzamide. 6. A compound according to Claim 3 where L3 is -N(R 7 )C(X)-, R 7 is alkyl of one to fifteen carbons, and W is O. 7. A compound according to Claim 6 selected from N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-chloro-N-methylbenzamide and N- [4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-2-chloro-4-nitro-N-methyl- 5 benzamide. 8. A compound according to Claim 3 where L3 is -N(R 7 )C(O)N(Rs)- and R 7 and Rs are hydrogen. -266- 9. A compound according to Claim 8 selected from ethyl 3-[[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-amino]carbonyl]- amino]benzoate, N- [4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol - -yl]phenyl]-N'-(3-cyanophenyl)urea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-N'-(3-nitrophenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-N'-(4-fluorophenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-N'-[4-(trifluoromethyl)- phenyl]urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl] phenyl] -N'- (3 , 5-dimethy lpheny 1) urea, N-[4-[3,5-bis(trifluoromethyl)- lH-pyrazol- -yl]phenyl]-N'-phenylurea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-N'-(3-chloro-2-methyl- phenyl)urea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-N'-[4-(butyloxyphenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-N'-(2-methyl-3-nitro- phenyl)urea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-N'-(2-chloro-4-nitro- phenyl)urea, N-(4-acetylphenyl)-N'-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-phenyl]urea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-N'-(4-methyl-2-nitro- phenyl)urea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-N'-(4-bromo-2,6-dimethy- lphenyPurea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol - -yl]phenyl]-N'-heptylurea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-N'-(4-chloro-2-nitro- phenyl)urea, N- [4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-N'-2-methyl-5-nitro- phenyl)urea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-N'-(4-bromo-2-methyl- phenyl)urea, and N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-N'-(4-chloro-3-nitro- phenyl)urea. 10. A compound according to Claim 3 where L3 is -NR 7 S(O)r, t is 2, and -267- R is hydrogen. 11. A compound according to Claim 10 that is N- [4- [3, 5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-3,5-difluorobenzene- sulfonamide. 12. A compound according to Claim 3 where L3 is -C(X)N(R )-, X is O, and R 7 is hydrogen. 13. A compound according to Claim 12 sei lected from 4-[3,5-bis(trifluoromethyl)-lH-pyrazoJ 1-1-ylJ- ■N-(4-fluorophenyl)benzamide, 4-[3,5-bis(trifluoromefhyl)-lH-pyrazoJ 1-1-ylJ- •N-(2-chlorophenyl)benzamide, 4 1--1[3^,5 ^--hbiissf(trriiffllιuιnorrnommpe.tthhvylπ)--1l HH--rpyrrΛaz7no 1-1-ylJ- N-(3-cyanophenyl)benzamide, 4- [3, 5-bis(trifluoromethyl)-l H-pyrazo 1-1-ylJ- ■N- (2 ,4-difluoropheny pbenzamide , 4- [3, 5-bis(trifluoromethyl)-l H-pyrazo I!-l-ylJ- N-(2-cyanophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazoj 1-1-ylJ- N-(2-nitrophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazo] 1-1-ylJ- N-(2,6-difluorophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazo 1]-1-ylJ- N-(2-bromophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazo] 1-1-ylJ- N-(4-cy anopheny pbenzamide , 4- [3, 5-bis(trifluoromethyl)-l H-pyrazo] 1-1-ylJ- N-(4-pyridinyl)benzamide, and N-[2-(aminocarbonyl)phenyl]-4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]benzamide. 14. A compound according to Claim 3 where L3 is -NR 7 (CH2) m - > R 7 is hydrogen, and m is 1. 15. A compound according to Claim 14 selected from N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] -2-chlorobenzenemethanamine and N- [4- [3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-4-fluorobenzenemethanamine. 16. A compound according to Claim 3 where L3 is -(CH2) m NR 7 -, R 7 is hydrogen, and m is 1. -268- 17. A compound according to Claim 16 selected from 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-N-(4-fluorophenyl)benzenemethanamine, 3-[4-[[[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]methyl]amino]benzonitrile, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-N-(2,4-difluorophenyl)benzene- methanamine, and 3 - [ [ [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]methyl]amino]benzonitrile. 18. A compound according to Claim 3 where L 3 is -C(H)=N-. 19. A compound according to Claim 18 that is (E)-N- [4- [3 ,5-bis(trifluoromethyP- 1 H-pyrazol- 1 -yl]phenylmethylene]-2,4- difluorobenzenamine . 20. A compound according to Claim 3 where L 3 is alkenylene of two to six carbons in the Z or E configuration. 21. A compound according to Claim 20 selected from (E)-3-[2-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]ethenyl]benzonitrile, (Z)-3-[2-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]ethenyl]benzonitrile, and (E)- 1 -[4-[2-(2-chlorophenyl)ethenyl]phenyl]-3,5-bis(trifluoromethyP- lH-pyrazole. 22. A compound according to Claim 2 where Z is carbon, R 2 is hydrogen, and R υ R 3 , and E are defined above, and R4 and R5 are independently selected from (1) hydrogen, (2) alkyl of one to fifteen carbons, (3) alkoxy of one to fifteen carbons, (4) halo, (5) perfluoroalkyl of one to fifteen carbons, (6) -CO 2 R 6 , (7) substituted heterocycle, -269- (8) -LιNR 7 R 8 , and (9) -CN. 23. A compound according to Claim 22 selected from N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-3-(trifluoromethyl)phenyl]-4-chloro- benzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl] -2-fluorophenyl] -2,4-difluoro- benzamide, N- [2,4-bis [3,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-2,4-difluorobenzamide, methyl 2-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-5-[(5-bromo-2-chlorobenzoyl)- amino]benzoate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-3-(trifluoromethyl)phenyl]-3,5- dimethyl-4-isoxazolecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-3-(trifluoromethyl)phenyl]-4-methyl- l,2,3-thiadiazole-5-carboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl] -3-chloroρhenyl]-3 ,5-dimethyl-4- isoxazolecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-2-(trifluoromethyl)phenyl]-3,5- dimethy 1-4-isoxazolecarboxamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-2-methylphenyl]-4-methyl-l,2,3- thiadiazole-5-carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-2-methoxyphenyl]-4-methyl-l,2,3- thiadiazole-5-carboxamide methyl 2-(3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl)-5-((2- fluorobenzoyl)amino)benzoate, N-(3-amino-4-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2-fluorobenzamide, and N-(4-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)-3-cyanophenyl)-2-fluorobenzanιide. 24. A compound according to Claim 2 where Rl is perfluoroalkyl of one to fifteen carbons and R is alkyl of one to fifteen carbons; 25. A compound according to Claim 24 selected from 4-chloro-N-[4-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]ρhenyl]benzamide, -270- 4-methyl-N-[4-[5-methyl-3-(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]- 1,2,3- thiadiazole-5-carboxamide, and 3,5-dimethyl-N-[4-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4- isoxazolecarboxamide. 26. A compound according to Claim 2 where Rl is hydrogen and R3 is alkyl of one to fifteen carbons. 27. A compound according to Claim 26 selected from 4-chloro-N- [4-(5-methyl- 1 H-pyrazol- 1 -yl)phenyl]benzamide, 4-methyl-N-[4-(5-methyl- 1 H-pyrazol- 1 -yPphenyl]- 1 ,2,3-thiadiazole-5-carboxamide, and 3,5-dimethyl-N-[4-(5-methyl- IH-pyrazol- 1 -yl)phenyl]-4-isoxazolecarboxamide. 28. A compound according to Claim 2 where Rl is perfluoroalkyl of one to fifteen carbons and R3 is hydrogen; 29. A compound according to Claim 28 that is 3,5-dimethyl-N-[4-[3-(trifluoromethyl)-lH-pyrazol-l-yl)ρhenyl]-4-isoxazole- carboxamide. 30. A compound according to Claim 2 where Rl is perfluoroalkyl of one to fifteen carbons and R3 is hydroxyl; 31. A compound according to Claim 30 that is N-[4-[5-hydroxy-3-(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-methyl- 1,2,3- thiadiazole-5-carboxamide. 32. A compound according to Claim 1 of formula -271- or a pharmaceutically acceptable salt or prodrug thereof, where Rl, R 2 , R3, R4, R5, Z, and E are defined above. 33. A compound according to Claim 32 selected from N-[3-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenylJ- 4-chlorobenzeneacetamide, N-[3-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]- 2,3-dichlorobenzamide, N-[3-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]- 2-chloro-5-nitrobenzamide, N-[3-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]phenyl]- 4-fluorobenzamide , N- [3 - [3 , 5 -bis (trifluoromethy 1) - 1 H-pyrazol- 1 -y 1] phenyl] - 2,4-difluorobenzamide, N- [3- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] - 3-cyanobenzamide, N-[3-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]- 2,6-difluorobenzamide, and N-[3-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]- 4-cyanobenzamide. 34. A compound according to Claim 1 of formula or a pharmaceutically acceptable salt or prodrug thereof, where Rl, R 2 , R3, R4, R5, Z, and E are defined above. 35. A compound according to Claim 34 selected from N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-2,6-difluorobenzamide and N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-ylJphenyl]-4-chlorobenzeneacetamide. 36. A compound according to Claim 1 of formula Rs R3 R c N-Q— E N I R or a pharmaceutically acceptable salt or prodrug thereof, where Q is heterocycle, and Ri, R 2 , R3, R4, R5, Z, and E are defined above. -272- 37. A compound according to Claim 36 selected from N-[2-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-5-pyridinyl]-2-chlorobenzamide, N-[2-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-5-pyridinyl]-3-cyanobenzamide, N-[2-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-5-pyridinyl]-2-chloro-4,5-difluoro- benzamide, N-(6-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)-3-pyridinyl)-2-fluorobenzamide, and N-(5-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)-2-pyridinyl)-2-fluorobenzamide. 38. A compound according to Claim 1 of formula R 3 4 R 5 or a pharmaceutically acceptable salt or prodrug thereof, where Z is nitrogen, and Ri, R3, R4, R5, and E are defined above. 39. A compound according to Claim 38 selected from 3 ,5-dimethyl-N-[4-(3 ,5-dimethyl- 1 H- 1 ,2,4-triazol- 1 -yPphenyl] -4- isoxazolecarboxamide and N- [4-(3,5-dimethyl- 1 H- 1 ,2,4-triazol- 1 -yPphenyl] -4-methyl- 1 ,2,3-thiadiazole-5- carboxamide. 40. A compound according to Claim 2 where R\ is -L 2 -heterocycle, and the heterocycle can be optionally substituted. 41. A compound according to Claim 40 selected from the group consisting of 3-fluoro-N-(4-(3-(4-pyridinyl)-5-(trifluoromethyl)- IH-pyrazol- 1 - yPphenyPisonicotinamide, N-(4-(5-(difluoromethyl)-3-(3-pyridinyl)-lH-pyrazol-l-yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-cyano-3-(2-pyridinyl)-lH-pyrazol-l-yl)phenyl)-3-fluoroisonicotinamide, -273- N-(4-(5-cyano-3-(3-pyridinyl)-l H-pyrazol- l-yl)phenyl)-4-methyl-l,2,3-thiadiazole-5- carboxamide, 3-fluoro-N-(4-(5-nitro-3-(3-pyridinyl)- IH-pyrazol- 1 -yPphenyPisonicotinamide, 4-methyl-N-(4-(5-nitro-3-(3-pyridinyl)- IH-pyrazol- 1 -yPphenyl)- 1 ,2,3-thiadiazole-5- carboxamide, N-(4-(5-cyano-3-( 1 ,3-thiazol-2-yl)- 1 H-pyrazol- 1 -yl)phenyl)-3-fluoroisonicotinamide, N-(4-(3-(5-bromo-3-pyridinyl)-5-(difluoromethoxy)- IH-pyrazol- l-yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-cyano-3-(l,3-thiazol-2-yl)-lH-pyrazol-l-yl)phenyl)-4-methyl-l,2,3- thiadiazole-5-carboxamide, N-(4-(5-cyano-3-( 1 ,3-thiazol-2-yl)- IH-pyrazol- 1 -yl)phenyl)-3-fluoroisonicotinamide, 4-methyl-N-(4-(3-( 1 ,3-thiazol-2-yl)-5-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)- 1 ,2,3-thiadiazole-5-carboxamide, N-(4-(3-(2,4-dimethyl-l,3-thiazol-5-yl)-5-(trifluoromethyP- IH-pyrazol- l-yl)phenyl)-3- fluoroisonicotinamide, 3-fluoro-N-(4-(3-tetrahydro-2-furanyl-5-(trifluoromethyl)-lH-pyrazol-l- yl)phenyl)isonicotinamide, N-(4-(5-chloro-3-( 1 ,3-thiazol-2-yl)- 1 H-pyrazol- 1 -yl)phenyl)-3-fluoroisonicotinamide, N-(4-(5-chloro-3-(3-furyl)-lH-pyrazol-l-yl)phenyl)-4-methyl-l,2,3-thiadiazole-5- carboxamide, N-(4-(5-chloro-3-(3-furyl)-l H-pyrazol- l-yl)phenyl)-3-fluoroisonicotinamide, N-(4-(5-cyano-3-tetrahydro-2-furanyl-lH-pyrazol-l-yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-(difluoromethoxy)-3-(l-methyl-lH-pyrrol-3-yl)-lH-pyrazol-l-yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-(difluoromethoxy)-3-(3-furyl)-lH-pyrazol-l-yl)phenyl)-3- fluoroisonicotinamide, and N-(4-(5-(difluoromethoxy)-3-( 1-methyl- 1 H-pyrrol-2-yl)- 1 H-pyrazol- 1 -yl)phenyl)-3- fluoroisonicotinamide. -274- 42. A compound selected from N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]cyclopropanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,2,3,3- tetramethylcyclopropane-carboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl] -2,2-dichloro- 1 - methylcyclopropanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-oxo-6-pentyl-2H-pyran- 3-carboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-3 ,5- difluorobenzenesulf onamide , N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yljphenyl]- 1-cyclohexene- 1 - carboxamide, N- [4- [3, 5-bis(trifluoromethyl)-l H-pyrazol- l-yl]phenyl]-2- methylcyclopropanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-ylJphenyl]-5-(3,5-dichlorophenoxy)- 2-furancarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl] - 1 -methyl-2-cyclohexene- 1 -carboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yljphenyl J- 1 -cyclopentene- 1 - carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-methoxycyclohexane- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-butynamide, ethyl 3-[[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]amino]carbonylJ- amino]benzoate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-furancarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-2-methyl-3- nitrobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl] -N'-(3-cyanophenyl)urea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]- 1 - hydroxycyclopropanecarboxamide, N-[4[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]cycloheptanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-benzofurancarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-5-fluoro- 1 H-indole-2- carboxamide, (E)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-(2-chlorophenyl)-2- propenamide, -275- 2-benzoyl-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, 3a(S)-(3aα,4β,6aα)-v-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 - yl]phenyl]hexahydro-2-oxo-lH-thieno[3,4-d]imidazole-4-pentanamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-3-iodobenzamide, exo-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]bicyclo[2.2.1]hept-5- ene-2-carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-methylcyclohexane- carboxamide, phenylmethyl [l-[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]amino]- carbonyl]propyl]carbamate, N-[4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl] -3-cyclohexene- 1 - carboxamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-N-(4-fluorophenyl)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-(3-nitrophenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-(4-fluorophenyl)urea, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-N'-[4-(trifluoromethyl)- phenyl]urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-(3,5- dimethylphenyPurea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l- methylcyclopropanecarboxamide, N- [4- [3, 5-bis(trifluoromethyl)-l H-pyrazol- 1 -yl]phenyl] -N'-phenylurea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-(3-chloro-2- methylphenyl)urea, N-[4-[3,5-bis(trifluoromethyP- IH-pyrazol- 1 -yl]phenyl]-N'-[4- (butyloxyphenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-(2-methyl-3- nitrophenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-(2-chloro-4- nitrophenyl)urea, N-(4-acety lphenyl)-N'- [4- [3, 5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]urea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-N'-(4-methyl-2- nitrophenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-methyl-2-thiophene- carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-(4-bromo-2,6-dimethyl- phenyl)urea, -276- 75 N-[4-[3,5-bis(trifluoromethyl)-lH-ρyrazol-l-yl]ρhenyl]-4-(lH-pyrrol-l- yPbenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-heptylurea, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-N'-(4-chloro-2-nitro- phenyl)urea, 80 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-7-methoxy-2- benzofurancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-2-methyl-5-nitro- phenyl)urea, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-(hydroxymethyl)- 85 benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-cyanoacetamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl] -2-cyclohexane- 1 - carboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl] -4- 90 methylcyclohexanecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-α-methoxy-α- (trifluoromethyl)benzeneacetamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]heptanamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-phenoxybenzamide, 95 3-amino-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, 4-amino-N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]benzamide, 4-azido-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, N- [4- [3 , 5 -bis(trifluoromethy 1)- 1 H-pyrazol- 1 -y 1] -2-thiopheneacetamide , N-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l-tricyclo[3.3.1.1 3 ' 7 ]decane- 100 carboxmide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N 2 -[(l,l-dimethylethoxy)- carbonyl]-l-asparagine, phenylmethyl ester, 1 , 1 -dimethylethyl [7- [[4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyl] amino] - 7-oxoheptyl]carbamate, 105 N-[4-[3,5-bis(trifluoromethyP- IH-pyrazol- 1 -yl]phenyl]-3- (methylthio)propanamide , N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]- 1 - naphthylenecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-cyanobenzamide, 110 trans-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2- phenylcyclopropane-carboxamide, -277- N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yPphenyl] -4-iodobenzamide , N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yPphenyl] - 3 -chloropropanamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yPphenyl] -4-methoxybenzamide, 115 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -y 1] phenyl] -2-ethy lhexanamide , N-[4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl] phenyl] -4-hydroxybenzamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yPphenyl] -4- (hexyloxy )benzamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-3-methylbenzamide, 2-(acetyloxy)-N- [4- [3 ,5-bis(trifluoromethyl - 1 H-pyrazol- 1 -yl]phenyl]benzamide, 120 N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-N'-(4-bromo-2- methylphenyPurea, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -y 1] phenyl] -2 ,4, 6-trimethy lbenzamide , N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-N'-(4-chloro-3- nitrophenyl)urea, 125 N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl] -2-chloro-N- methy lbenzamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2-chloro-4-nitro-N- methylbenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2- 130 chlorobenzenemethanamine, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]- 1 -methyl-5-nitro- 1 H- pyrazole-4-carboxamide, N- [4- [3 , 5 -bis(trifluoromethy 1) - 1 H-pyrazol- -yl]phenyl]-4- fluorobenzenemethanamine , 135 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-4-bromobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2- (dimethylamino)benzamide , N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-3- (dimethylamino)benzamide , 140 N-[4-[3,5-bis(trifluoromethyl)- lH-pyrazol- -yl]phenyl]-4- (trifluoromethyl)benzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-4-fluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2-chlorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]benzamide, 145 N-[4-[3,5-bis(trifluoromethyP- lH-pyrazol- -yl]phenyl]-4-nitrobenzamide, 4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl] •N-(4- fluorophenyPbenzenemethanamine , -278- 3-[4-[[[3,5-bis(trifluoromethyl)-lH-pyrazol-l- yl]phenyl]methyl]amino]benzonitrile, 150 N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyl] -2-methy lbenzamide, (E)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenylmethylene]-2,4- difluoro-benzenamine, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-4-dimethoxybenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]cyclopentanepropanamide, 155 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-methylbenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3- (trifluoromethyl)benzamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-3-methyl-2-butenamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyl] -2-hydroxybenzamide, 160 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-hydroxybenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,4-dimethyl-5- thiazolecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4- 165 (hydroxymethyl)benzamide, 4-[3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl]-N-(2,4- difluorophenyPbenzenemethanamine, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-4- (methylsulfony benzamide , 170 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-iodobenzamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-4-heptybenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-fluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-N'-methyl-l,2- 175 benzenedicarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-chloro-2- nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-cinnolinecarboxamide, 180 4-acetyl-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, 1 , 1 -dimethylethyl 4- [ [[4- [3 ,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yPphenyl] - amino] carbonyl]- 1 -piperidinecarboxylate, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyl] -2-pyridinecarboxamide, -279- N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-4- 185 (diethylamino)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]cyclopentanecarboxmide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]cyclohexanecarboxmide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-piperidinecarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-3- 190 (methylsulfonyPbenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2- (trifluoromethyl)benzamide, 3-[[[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1- yl]phenyl]methyl]amino]benzonitrile, 195 methyl 3-[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l- yl]phenyl]amino]carbonyl]benzoate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-chlorobenzamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-2-thiophenecarboxamide, (E)-3-[2-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]ethenyl]benzonitrile, 200 N-[4-[3,5-bis(trifluoromethyP- lH-pyrazol-1 -yPphenyl]- 1 ,4- benzenedicarboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-3,5-dinitrobenz amide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,4-difluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-nitrobenzamide, 205 N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-3-cyanobenzamide, N- [4-[3 ,5-bis(trifluoromethyP- 1 H-pyrazol- 1 -yPphenyl] -1,3- benzenedicarboxamide, (Z)-3-[2-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]ethenyl]benzonitrile, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-3-nitrobenzamide, 210 3-(aminosulfonyl)-N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 - yPphenyPbenzamide, methyl 4-[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l- yl]phenyl]amino]carbonyl]benzoate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-methoxybenzamide, 215 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-bromobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyl] -3 -methoxybenzamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-3-fluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-bromobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyl] - 1 ,3-benzodioxole-5- 220 carboxamide, -280- N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,6-dichloro-3- pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-2-chloro-3- pyridinecarboxamide, 225 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-chloro-6-methyl-3- pyridinecarboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-4-fluoro-γ- oxobenzenebutanamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l,2,3,4-tetrahydro-2- 230 naphthalenecarboxamide, (E)-l-[4-[2-(2-chlorophenyl)ethenyl]phenyl]-3,5-bis(trifluoromethyl)-lH-pyrazole, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-(4-chlorophenoxy)-2- methylpropanamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]acetamide, 235 4- [ [ [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyl] amino]carbonyl]benzoic acid, phenylmethyl N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyl] amino] -4- oxobuty 1] carbamate , 3-[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]amino]carbonyl]benzoic 240 acid, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-2,6-difluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyP- 1 H-pyrazol- 1 -yl]phenyl]-3 -bromo-2- thiophenecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-methyl-2- 245 thiophenecarboxamide, 2-amino-N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-fluoro-3- pyridinecarboxamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-chloro-4- 250 (methylsulfonyl)- 2-thiophenecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-lH-pyrrole-2- carboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-3,6-dichloro-2- 255 pyridinecarboxamide N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-(2- nitrophenoxy)acetamide, -281- N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4- chlorobenzeneacetamide, 260 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-lH-indole-2-acetamide, (E)-N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-(2-thienyl)-2- propenamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]py azinecarboxamide, 1,1-dimethylethyl [[4-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -y phenyl] amino] - 265 4-oxobutyl]carbamate, 1 -acetyl-N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yljphenyl] -4- piperidinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]butanamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-chloro-2- 270 methoxybenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-α-methyl-4-(2-thienyl- carbonyl)benzeneacetamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]phenyl]-α-methy l-4-(2-thienyl- carbonyPbenzeneacetamide, 275 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-methoxy-4- (methy thio)benzamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-hydroxy-3- nitrobenzamide, N- [4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyl] -3 ,4-dihydroxybenzamide, 280 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-hydroxy-6- methoxybenzamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,4- bis(trifluoromethyl)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-methyl-4- 285 isoxazolecarboxamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-N-(2-chlorophenyl)benzamide, 4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]-N-(3-cyanophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yP-N-(2,4-difluorophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-N-(2-cyanophenyl)benzamide, 290 N-[4-[5-[3,5-dimethyl-lH-l,2,4-triazol-l-yl)-3-(trifluoromethyl)-lH-pyrazol-l- yl]phenyl]-4-isoxazolecarboxamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-N-(2-nitrophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-N-(2,6-difluorophenyl)benzamide, 4- [3 ,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yP-N-(2-bromophenyl)benzamide, -282- 295 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-N-(4-cyanophenyl)benzamide, 4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-N-(4-pyridinyl)benzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-fluoro-3-(trifluoro- methyPbenzamide, N-[2-(aminocarbonyl)phenyl]-4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l- 300 yl]benzamide, N-[3-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4- chlorobenzeneacetamide, N-[3-[3,5-bis(trifluoromethyl yl]phenyl]-2,3-dichlorobenzamide, N- [3 - [3 , 5 -bis(trifluoromethyl -yl]phenyl]-2-chloro-5- 305 nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl -yl]phenyl]-4-fluoro-3- nitrobenzamide, N- [4- [3 ,5-bis(trifluoromethyl -yl]phenyl]-4-fluoro-3- nitrobenzamide, 310 N-[4-[3,5-bis(trifluoromethyl -yl]phenyl]-4-fluoro-2- (trifluoromethyl)-benzamide, N- [3- [3 ,5-bis(trifluoromethyl -yPphenyl] -4-fluorobenzamide , N-[3-[3,5-bis(trifluoromethyl -yPphenyl] -2 ,4-difluorobenzamide , N-[3-[3,5-bis(trifluoromethyl -yl]phenyl]-3-cyanobenzamide, 315 N- [4- [3 ,5-bis(trifluoromethyl -yl]phenyl]-2-bromo-3- nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl -yl] phenyl] -2-chloro-4-fluoro- benzamide, N-[4-[3,5-bis(trifluoromethyl -yl]phenyl]-2-chloro-4- 320 (methylsulfonyl)-benzamide, N-[4-[3,5-bis(trifluoromethyl -y 1] phenyl] -2, 5-dichlorobenzamide , N- [4- [3 ,5-bis(trifluoromethyl -yl]phenyl]-2,3-difluorobenzamide, N-[4- [3 ,5-bis(trifluoromethyl -yl]phenyl]-3-chloro-4- fluorobenzamide, 325 N-[4-[3,5-bis(trifluoromethyl -yl]phenyl]-2,5-difluorobenzamide, N-[4-[3,5-bis(trifluoromethyl -yl]phenyl]-2-chloro-6- fluorobenzamide , N- [4- [3 ,5 -bis(trifluoromethyl -yl]phenyl]-2-fluoro-6- (trifluoromethyl)-benzamide, 330 N-[4-[3,5-bis(trifluoromethyl -yl]phenyl]-3-chloro-2- fluorobenzamide, -283- N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2-chloro-4- methoxybenzamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2,6-dichloro-3- 335 nitrobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yPphenyl] -4-bromo-2- chlorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-3,4-difluorobenz amide, N- [4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl] phenyl] -2-bromo-5- 340 methoxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-4-chloro-2- hydroxybenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-3-bromo-4- methoxybenzamide , 345 N- [4- [3 ,5-bis(trifluoromethyP- 1 H-pyrazol- -yl]phenyl]-3-bromo-4- hydroxybenzamide , N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2-chloro-4,5- difluorobenzamide, N-[3-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2,6-difluorobenzamide, 350 N-[4-[3,5-bis(trifluoromethyl)- lH-pyrazol- -yl]phenyl]-4-chloro-2,5- difluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2,3,4-trifluorobenz amide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-3,4,5-trifluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2,4,5-trifluorobenz amide, 355 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2,4,6-trifluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2,6-difluoro-3- nitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2,3,5-trifluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2,4-dichloro-6- 360 fluorobenzamide, N-4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 yl]phenyl-2,4-dichloro-3 ,5- dinitrobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yPphenyl] -2,3 ,5 ,6-tetrafluoro- benzamide, 365 N-[4-[3,5-bis(trifluoromethyl)- lH-pyrazol- -yPphenyP-2,3,4,5- tetrafluorobenzamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-4-bromo-2, 3,5,6- tetrafluorobenzamide , -284- N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-5-methyl-2- 370 nitrobenzamide, N-[3-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-cyanobenzamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-3-thiophenecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyP-5-isoxazolecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]tetrahydro-2- 375 furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]-2-pyrrolidinecarboxamide, N- [4- [3, 5-bis(trifluoromethyl)-l H-pyrazol- l-yl]phenyl]tetrahydro-3- furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l,2,3-thiadiazole-5- 380 carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2-chloro-4- pyridinecarboxamide, 1,1-dimethylethyl 2-[[[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l- yl]phenyl]amino]carbonyl]- 1 -pyrrolidinecarboxylate, 385 N- [4- [3, 5-bis(trifluoromethyl)- IH-pyrazol- 1 -yPphenyl] -5-nitro-2- furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-l-methyl-lH-pyrrole-2- carboxamide, N- [4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyl] -6-chloro-3- 390 pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-bromo-2- furancarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-3-methyl-2- furancarboxamide, 395 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-chloro-2- thiophenecarboxamide, (S)-N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]phenyl]tetrahydro-5-oxo-2- furan-carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-oxo-2- 400 pyrrolidinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-bromo-3- pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-nitro-3-thiophene- carboxamide, -285- 405 1,1 -dimethylethyl 4- [ [[4-[3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyl] amino] - carbonyl]-3-thiazolidinecarboxylate, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-5-methoxy-3- thiophenecarboxamide, N-[2-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]-5-pyridinyl]-2-chlorobenzamide, 410 N- [2- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]-5-pyridinyl]-3-cyanobenzamide, N-[2-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]-5-pyridinyl]-2-chloro-4,5- difluorobenzamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yl]phenyl]-2,3-dibromo-5- thiophenecarboxamide, 415 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-3-fluoro-4-pyridine— carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yPphenyl]- 1 -methyl- 1 H-pyrazole-4- carboxamide, N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- -yPpheny 1] - 5 -chloro-4-methoxy- 3 - 420 thiophenecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yPphenyl] -5 ,6-dichloro-3- pyridinecarboxamide N- [4- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol - -yl]phenyl]-2,6-dichloro-4- pyridinecarboxamide, 425 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]phenyl]-2,5-dichloro-3- pyridinecarboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]-3-(trifluoromethyl)phenyl]-4- chlorobenzamide , N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol- -yl]-2-fluorophenyl]-2,4- 430 difluorobenzamide, N-[2,4-bis[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-2,4- difluorobenzamide, methyl 2- [3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl]-5- [(5-bromo-2- chlorobenzoyl)amino]benzoate, 435 N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-3-(trifluoromethyl)phenyl]-3,5- dimethyl-4-isoxazolecarboxamide, N-[4-[3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl]-3-(trifluoromethyl)phenyl]-4- methyl- 1 ,2,3-thiadiazole-5-carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-3-chlorophenyl]-3,5-dimethyl-4- 440 isoxazolecarboxamide, -286- N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-2-(trifluoromethyl)phenyl]-3,5- dimethyl-4-isoxazolecarboxamide, N-[4-[3,5-bis(trifluoromethyP- IH-pyrazol- l-yl]-2-methylphenyl]-4-methyl- 1 ,2,3- thiadiazole-5-carboxamide, N-[4-[3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl]-2-methoxyphenyl]-4-methyl- 1 ,2,3-thiadiazole-5-carboxamide, 4-chloro-N-[4-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]benzamide, 4-methyl-N-[4-[5-methyl-3-(trifluoromethyl)- IH-pyrazol- 1 -yPphenyl]- 1 ,2,3- thiadiazole-5-carboxamide, 3,5-dimethyl-N-[4-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4- isoxazolecarboxamide, 4-chloro-N- [4-(5-methyl- 1 H-pyrazol- 1 -yl)phenyl]benzamide, 4-methyl-N-[4-(5-methyl- 1 H-pyrazol- 1 -yPphenyl]- 1 ,2,3-thiadiazole-5- carboxamide, 3,5-dimethyl-N-[4-(5-methyl-lH-pyrazol-l-yl)phenyl]-4-isoxazolecarboxamide, 3,5-dimethyl-N-[4-[3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyP-4- isoxazolecarboxamide, N-[4-[5-hydroxy-3-(trifluoromethyl)-lH-pyrazol-l-yl]phenyl]-4-methyl-l,2,3- thiadiazole-5-carboxamide, N- [4- [5-(3 ,5-dimethyl- 1 H- 1 ,2,4-triazol- 1 -yl)-3-(trifluoromethyl)- 1 H-pyrazol- 1 - yPphenyl]- 1 ,2,3-thiadoazole-5-carboxamide, 3-amino-N-(4-(3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyPisonicotinamide, N-(4-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-3-chloro-5- methoxyisonicotinamide , N-(6-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)-3-pyridinyl)-2-fluorobenzamide, methyl 2-(3,5-bis(trifluoromethyl)- IH-pyrazol- 1 -yl)-5-((2- fluorobenzoyl)amino)benzoate, 4-(aminomethyl)-N-(4-(3,5-bis(trifluoromethyl)- IH-pyrazol- l-yl)phenyl)-2- chlorobenzamide, N-(4-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2-methylacrylamide, N-(4-(3 ,5-bis(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-4-chloro-2- fluorobenzamide , N-(5-(3,5-bis(trifluoromethyl)-l H-pyrazol- l-yl)-2-pyridinyl)-2-fluorobenzamide, N-(3-amino-4-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yPphenyl)-2- fluorobenzamide, N-(4-(3,5-bis(trifluoromethyl)-lH-pyrazol-l-yl)-3-cyanophenyl)-2- fluorobenzamide, N-(4-(5-cyano-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2-fluorobenzamide, -287- 2-fluoro-N-(4-(5-(2-furyl)-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyPbenzamide, N-(4-(5-cyano-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-4-methyl- 1,2,3- 480 thiadiazole-5-carboxamide, N-(4-(5-cyano-3-(trifluoromethyl)- IH-pyrazol- 1 -yPphenyPisonicotinamide, N-(4-(5-cyano-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-acetyl-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-2-fluorobenzamide, 485 N-(4-(5-cyano-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2-fluoronicotinamide, N-(4-(5-cyano-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2,3,5- trifluorobenzamide , 2-fluoro-N-(4-(5-(2-thienyl)-3-(trifluoromethyP- IH-pyrazol- 1- yPphenyPbenzamide, 490 2-fluoro-N-(4-(5-(methylsulfanyl)-3-(trifluoromethyl)-l H-pyrazol- 1- yPphenyPbenzamide, 2-fluoro-N-(4-(5-(3-pyridinyl)-3-(trifluoromethyl)-l H-pyrazol- 1- yl)phenyl)benzamide, 3-fluoro-N-(4-(5-(2-thienyl)-3-(trifluoromethyP- IH-pyrazol- 1- 495 yPphenyPisonicotinamide, N-(4-(5-methoxy-3-(trifluoromethyl)-l H-pyrazol- 1 -yPphenyPisonicotinamide, 2-fluoro-N-(4-(5-methoxy-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)benzamide, N-(4-(5-methoxy-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-4-methyl-l,2,3- thiadiazole-5-carboxamide, 500 N-(4-(5-acetyl-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-2-fluoronicotinamide, 2-fluoro-N-(4-(5-(methylsulfanyl)-3-(trifluoromethyl)-lH-pyrazol-l- yl)phenyl)nicotinamide, 2-fluoro-N-(4-(5-methoxy-3-(trifluoromethyl)-lH-pyrazol-l- yl)phenyl)nicotinamide, 505 N-(4-(5-ethoxy-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-2-fluoronicotinamide, 3-fluoro-N-(4-(5-(methylsulfanyl)-3-(trifluoromethyl)- IH-pyrazol- 1- yl)phenyl)isonicotinamide, 3-fluoro-N-(4-(5-methoxy-3-(trifluoromethyl)-lH-pyrazol-l- yPphenyPisonicotinamide, 510 N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)-lH-pyrazol-l- yl)phenyl)isonicotinamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-4-methyl- 1 ,2,3-thiadiazole-5-carboxamide, -288- N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-2- 515 fluoronicotinamide , N-(4-(5-chloro-3-(trifluoromethyl)-lH-pyrazol-l-yl)phenyl)-2-fluoronicotinamide, 2-fluoro-N-(4-(5-nitro-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)benzamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-3- fluoroisonicotinamide, 520 N-(4-(5-chloro-3-(trifluoromethyl)-l H-pyrazol- l-yl)phenyl)-3-fluoroisonicotinamide, N-(4-(5-bromo-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-3-fluoroisonicotinamide, 3-fluoro-N-(4-(5-nitro-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yPphenyPisonicotinamide, N-(4-(5-bromo-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)-4-methyl- 1 ,2,3- thiadiazole-5-carboxamide, 525 N-(4-(5-chloro-3-(trifluoromethyl)-lH-l,2,4-triazol-l-yl)phenyl)-3- fluoroisonicotinamide, 3-fluoro-N-(4-(5-(l-methyl-lH-pyrrol-3-yl)-3-(trifluoromethyl)-lH-pyrazol-l- yPpheny Pisonicotinamide , 3-chloro-N-(4-(5-chloro-3-(trifluoromethyl)-l H-pyrazol- 1 -yPphenyPisonicotinamide, 530 N-(4-(5-bromo-3-(trifluoromethyl)- IH-pyrazol- l-yl)phenyl)-2,3- difluorobenzamide , N-(4-(5-bromo-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-3- chloroisonicotinamide, 2-chloro-N-(4-(5-cyano-3-(trifluoromethyl)- 1 H-pyrazol- 1 -yl)phenyl)benzamide, 535 3-chloro-N-(4-(5-cyano-3-(trifluoromethyl)-lH-pyrazol-l- yPphenyPisonicotinamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)-2- fluorobenzamide , 2-chloro-N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- IH-pyrazol- 1 - 540 yPphenyPbenzamide, N-(4-(5-(difluoromethoxy)-3-(trifluoromethyl)- IH-pyrazol- l-yl)phenyl)-2,3- difluorobenzamide , 3-fluoro-N-(4-(3-(4-pyridinyl)-5-(trifluoromethyl)-lH-pyrazol-l- yPphenyPisonicotinamide, 545 N-(4-(5-(difluoromethyl)-3-(3-pyridinyl)- IH-pyrazol- l-yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-cyano-3-(2-pyridinyl)-l H-pyrazol- l-yl)phenyl)-3-fluoroisonicotinamide, N-(4-(5-cyano-3-(3-pyridinyl)-lH-pyrazol-l-yl)phenyl)-4-methyl-l,2,3- thiadiazole-5-carboxamide, 550 3-fluoro-N-(4-(5-nitro-3-(3-pyridinyl)- IH-pyrazol- 1 -yPphenyPisonicotinamide, -289- 4-methyl-N-(4-(5-nitro-3-(3-pyridinyl)-lH-pyrazol-l-yl)phenyl)-l,2,3-thiadiazole- 5-carboxamide, N-(4-(5-cyano-3-( 1 ,3-thiazol-2-yl)- 1 H-pyrazol- 1 -yl)phenyl)-3- fluoroisonicotinamide , 555 N-(4-(3-(5-bromo-3-pyridinyl)-5-(difluoromethoxy)- IH-pyrazol- 1 -yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-cyano-3-( 1 ,3-thiazol-2-yl)- IH-pyrazol- 1 -yl)phenyl)-4-methyl- 1,2,3- thiadiazole-5-carboxamide, N-(4-(5-cyano-3-( 1 ,3-thiazol-2-yl)- IH-pyrazol- 1 -yl)phenyl)-3- 560 fluoroisonicotinamide, 4-methyl-N-(4-(3-( 1 ,3-thiazol-2-yl)-5-(trifluoromethyl)- IH-pyrazol- 1 -yl)phenyl)- 1 ,2,3-thiadiazole-5-carboxamide, N-(4-(3-(2,4-dimethyl-l,3-thiazol-5-yl)-5-(trifluoromethyP- IH-pyrazol- 1- yl)phenyl)-3-fluoroisonicotinamide, 565 3-fluoro-N-(4-(3-tetrahydro-2-furanyl-5-(trifluoromethyl)- IH-pyrazol- 1- yPphenyPisonicotinamide, N-(4-(5-chloro-3-( 1 ,3-thiazol-2-yl)- 1 H-pyrazol- 1 -yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-chloro-3-(3-furyl)- IH-pyrazol- 1 -yl)phenyl)-4-methyl- 1 ,2,3-thiadiazole-5- 570 carboxamide, N-(4-(5-chloro-3-(3-furyl)- IH-pyrazol- 1 -yl)phenyl)-3-fluoroisonicotinamide, N-(4-(5-cyano-3-tetrahydro-2-furanyl- IH-pyrazol- l-yl)phenyl)-3- fluoroisonicotinamide, N-(4-(5-(difluoromethoxy)-3-( 1 -methyl- 1 H-pyrrol-3-yl)- IH-pyrazol- 1 -yl)phenyl)- 575 3-fluoroisonicotinamide, N-(4-(5-(difluoromethoxy)-3-(3-furyl)-lH-pyrazol-l-yl)phenyl)-3- fluoroisonicotinamide, and N-(4-(5-(difluoromethoxy)-3-( 1 -methyl- lH-pyrrol-2-yl)- 1 H-pyrazol- 1 -yl)phenyl)- 3-fluoroisonicotinamide. 580 -290- 43. A method of inhibiting interleukin-2, interleukin-4, and interleukin-5 production in a mammal comprising adminstering a therapeutically effective amount of a compound of Claim 1. 44. A method of treating immunologically-mediated diseases in a mammal comprising administering a therapeutically effective amount of a compound of Formula I R, R y I N— Q— E I R 5 I or a pharmaceutically acceptable salt or prodrug thereof, where Rl and R3 are independently selected from (1) hydrogen, (2) aryl, (3) perfluoroalkyl of one to fifteen carbons, (4) halo, (5) -CN, (6) -NO2, (7) -OH, (8) -OG where G is a hydroxyl protecting group, (9) -CO2R6 where R6 is selected from (a) hydrogen, (b) cycloalkyl of three to twelve carbons, (c) aryl, (d) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, (ii) alkoxy of one to fifteen carbons, (iii) thioalkoxy of one to fifteen carbons, (iv) halo, (v) -NO2, and (vi) -N 3 , -291- (e) a carboxy protecting group, (f) alkyl of one to fifteen carbons, (g) alkyl of one to fifteen carbons substituted with 1, 2, or 3, or 4 substituents independently selected from (i) alkoxy of one to fifteen carbons, (ii) thioalkoxy of one to fifteen carbons, (iii) aryl, (iv) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from alkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, -NO 2 , and -N 3 , (v) cycloalkyl of three to twelve carbons, and (vi) halo, (h) alkenyl of three to fifteen carbons, provided that a carbon of a carbon-carbon double bond is not attached directly to oxygen, (i) alkynyl of three to fifteen carbons, provided that a carbon of a carbon-carbon triple bond is not attached directly to oxygen, and (j) cycloalkyl of three to twelve carbons, (10) -LιNR 7 R8 where Li is selected from (a) a covalent bond, (b) -X'C(X)- where X and X' are independently O or S, (c) -C(X)-, and (d) -NR 6 - and R 7 and Rs are independently selected from (a) hydrogen, (b) alkanoyl where the alkyl part is one to fifteen carbons, (c) alkoxycarbonyl where the alkyl part is one to fifteen carbons, (d) alkoxycarbonyl where the alkyl part is one to fifteen carbons and -292- is substituted with 1 or 2 substituents selected from the group consisting of aryl, (e) cycloalkyl of three to twelve carbons, (f) aryl, (g) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, (ii) alkoxy of one to fifteen carbons, (iii) thioalkoxy of one to fifteen carbons, (iv) halo, (v) -NO 2 , and (vi) -N 3 , (h) -OR 6 , provided that only one of R 7 or Rs is -ORβ, (i) a nitrogen protecting group, (j) alkyl of one to fifteen carbons, (k) alkyl of one to fifteen carbons substituted with 1, 2, or 3, or 4 substituents independently selected from (i) alkoxy of one to fifteen carbons, (ii) thioalkoxy of one to fifteen carbons, (iii) aryl, (iv) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from alkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, -NO 2 , and -N 3 , (v) cycloalkyl of three to fifteen carbons, (vi) halo, (vii) -CO 2 R6, and (viii) -OH, (1) alkenyl of three to fifteen carbons, -293- provided that a carbon of a carbon-carbon double bond is not attached directly to nitrogen, (m) alkynyl of three to fifteen carbons, provided that a carbon of a carbon-carbon triple bond is not 100 attached directly to nitrogen, (n) -SO 2 -alkyl, and (o) cycloalkyl of three to twelve carbons, or R 7 and Rs together with the nitrogen atom to which they are attached form a ring selected from 105 (i) aziridine, (ii) azetidine, (iii) pyrrolidine, (iv) piperidine, (v) piperazine, 110 (vi) morpholine, (vii) thiomorpholine, and (viii) thiomorpholine sulfone where (i)-(viii) can be optionally substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl of one to fifteen 115 carbons, (11) -L2R9 where L 2 is selected from (a) -Li-, (b) -O-, and (c) -S(O) t - where t is 0, 1 , or 2 and 120 R9 is selected from (a) cycloalkyl of three to twelve carbons, (b) aryl (c) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from 125 (i) alkyl of one to fifteen carbons, (ii) alkoxy of one to fifteen carbons, (iii) thioalkoxy of one to fifteen carbons, (iv) halo, (v) -NO2, and -294- 130 (vi) -N 3 , (d) alkyl of one to fifteen carbons, (e) heterocycle, (f) alkenyl of two to fifteen carbons, and (e) alkyl of one to fifteen carbons substituted with 1, 2, or 3, or 4 135 substituents independently selected from (i) alkenyl of two to fifteen carbons, (ii) alkoxy of one to fifteen carbons, (iii) -CN, (iv) -CO 2 R 6 , 140 (v) -OH, provided that no two -OH groups are attached to the same carbon, (vi) thioalkoxy of one to fifteen carbons, (vii) alkynyl of two to fifteen carbons, 145 (viii) aryl, (ix) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from alkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, 150 thioalkoxy of one to fifteen carbons, halo, -NO , and -N 3> (x) cycloalkyl of three to twelve carbons, and 155 (xi) halo, (xii) -NR 7 R 8 , (xiii) heterocycle, and (xiv) heterocycle substituted with 1, 2, or 3, or 4 substituents independently selected from 160 alkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, -295- -NO 2 , and 165 -N 3 , (12) alkyl of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 halo substituents, (13) alkyl of one to fifteen carbons, (14) alkenyl of two to fifteen carbons, (15) alkynyl of two to fifteen carbons 170 where (13)-(15) can be optionally substituted with (a) (=X), (b) alkanoyloxy where the alkyl part is one to fifteen carbons, (c) alkoxy of one to fifteen carbons, (d) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents 175 selected from the group consisting of halo, (e) thioalkoxy of one to fifteen carbons, (f) perfluoroalkoxy of one to fifteen carbons, (g) -N 3 , (h) -NO 2 , 180 (i) -CN, G) -OH, (k) -OG (1) cycloalkyl of three to twelve carbons, (m) halo, 185 (n) -CO 2 R 6 , (o) -LιNR 7 R 8 , and (p) - 2 R 9 , (16) -L 2 -heterocycle, and (17) -L 2 -heterocycle where the heterocycle is substituted with 1, 2, 3 or 4 190 substituents independently selected from (a) alkyl of one to fifteen carbons, (b) perfluoroalkyl of one to fifteen carbons, (c) alkoxy of one to fifteen carbons, (d) thioalkoxy of one to fifteen carbons, 195 (e) halo, and ( ) -NO 2 , (18) -NRχC(O)NRγRz where Rx, RY and Rz are independently selected from -296- (a) hydrogen and (b) alkyl of one to fifteen carbons, 200 (19) -C(=NRχ)NRγR z , (20) -NRχC(=NRχ')NRγRz where Rχ ; RY and Rz are defined previously and Rχ > is selected from (a) hydrogen and (b) alkyl of one to fifteen carbons, 205 (21) -NRχC(O)OR \ v, where R v is selected from (a) alkyl of one to fifteen carbons and (b) alkenyl of three to fifteen carbons, provided that a carbon of a carbon-carbon double bond is not attached directly to oxygen, and 210 (22) -OC(O)NR 7 R 8 ; Z is nitrogen or carbon; R 2 is absent or is selected from 215 (1) hydrogen, (2) -CO 2 R 6 , (3) alkyl of one to fifteen carbons, (4) -C(O)R6' where R& is selected from (a) alkyl of one to fifteen carbons, 220 (b) aryl, and (c) heterocycle, (5) -C(O)NR7'R8' where R7' and Rs 1 are independently selected from (a) hydrogen, (b) alkyl of one to fifteen carbons, or 225 R7' and Rs' together with the nitrogen to which they are attached form a ring selected from (i) piperidine, (ii) piperazine, (iii) morpholine, 230 (iv) thiomorpholine, and (v) thiomorpholine sulfone -297- (6) perfluoroalkyl of one to fifteen carbons, (7) cycloalkyl of three to ten carbons, (8) alkyl of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents 235 selected from the group conststing of halo, (9) alkyl of one to fifteen carbons substituted with (a) -CN, (b) -OH, provided that no two -OH groups are attached to the same carbon, 240 (c) (=X), and (d) -CO 2 R 6 , and (10) halogen; provided that when X is nitrogen, R is absent; 245 Q is aryl or heterocycle where, when Q is phenyl, the phenyl is 2-, 3-, or 4- substituted by E relative to the position of attachment of the pyrazole or 1,2,4-triazole ring to the phenyl ring; R4 and R5 are independently selected from 250 (1) hydrogen, (2) alkyl of one to fifteen carbons, (3) alkyl of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 halo substituents, (4) alkyl of one to fifteen carbons substituted with (a) -CN, 255 (b) -CO 2 R 6 , (c) -LιNR 7 R 8 , and (d) -L 2 R 9 , (5) perfluoroalkyl of one to fifteen carbons, (6) -CN, 260 (7) -CO 2 R 6 , (8) -LιNR 7 R 8 , (9) -L 2 R 9 , ( 10) alkoxy of one to fifteen carbons, (11) thioalkoxy of one to fifteen carbons, 265 (12) halo, -298- (13) -C(=NR 6 )NR 7 R 8 , (14) -NRι 2 (=NR6)NR 7 Rs where Re, R 7 , and Rs are defined previously and Rι 2 is selected from (a) hydrogen, 270 (b) cycloalkyl of three to twelve carbons, (c) aryl, (d) alkyl of one to fifteen carbons, and (e) alkyl of one to fifteen carbons substituted with 1, 2, or 3, or 4 substituents independently selected from 275 (i) alkenyl of two to fifteen carbons, (ii) alkoxy of one to fifteen carbons, (iii) thioalkoxy of one to fifteen carbons, (iv) alkynyl of two to fifteen carbons, and (v) aryl, 280 (15) -L 2 -heterocycle, and (16) -L -heterocycle where the heterocycle is substituted with 1, 2, 3, or 4 substituents independently selected from (a) alkyl of one to fifteen carbons, (b) perfluoroalkyl of one to fifteen carbons, 285 (c) alkoxy of one to fifteen carbons, (d) thioalkoxy of one to fifteen carbons, (e) halo, (f) -N 3 , and (g) -NO 2 ; 290 E is (1) -L 3 -B where L 3 is selected from (a) a covalent bond, (b) alkenylene of two to six carbons in the Z or E configuration, 295 (c) alkynylene of two to six carbons, (d) -C(X)-, (e) -N=N-, ω -NR 7 -, (g) -N(R 7 )C(O)N(R 8 )-, -299- 300 (h) -N(R 7 )SO 2 N(R 8 )-, (i) -X-, (j) -(CH 2 ) m O-, (k) -O(CH 2 ) m -, (1) -N(R 7 )C(X)-, 305 (m) -C(X)N(R 7 )-, (n) -S(O) t (CH 2 ) m -, (o) -(CH 2 ) m S(O) r , (p) -NR 7 (CH 2 ) m -, (q) -(CH 2 ) m NR 7 -, 310 (r) -NR 7 S(O) t -, (s) -S(O) t NR 7 -, (t) -N=C(H)-, (u) -C(H)=N-, (v) -ON=CH-, 315 (w) -CH=NO- where (g)-(w) are drawn with their left ends attached to Q, (x) -N(R 7 )C(O)N(Rιo)(Rι ι)- where Rio and Ri i together with the nitrogen atom to which they are attached form a ring selected from (i) morpholine, 320 (ii) thiomorpholine, (iii) thiomorpholine sulfone, and (iv) piperidine where (i)-(iv) are attached to Q through the nitrogen to which is attached R 7 and to B through a carbon in the ring, 325 (y) -N(R 7 )SO 2 N(Rιo)(Rn)-, and (z) -N(R 7 )C(O)N(Rιo)(Rn)- and B is selected from (a) alkyl of one to fifteen carbons, (b) alkenyl of three to fifteen carbons in the E or Z configuration, 330 provided that a carbon of a carbon-carbon double bond is not directly attached to L3 when L 3 is other than a covalent bond, (c) alkynyl of three to fifteen carbons, provided that a carbon of a carbon-carbon triple bond is not directly -300- attached to L 3 when L3 is other than a covalent bond 335 where (a), (b) and (c), can be optionally substituted with 1, 2, 3, or 4 substituents independently selected from RB R A\ ^Rc (i) R E where L 2 is defined previously and RA, RB» Rc, RD > and RE are independently selected from hydrogen, 340 alkanoyl where the alkyl part is one to fifteen carbons, alkanoyloxy where the alkyl part is one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, 345 alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo , perfluoroalkyl of one to fifteen carbons, perfluoroalkoxy of one to fifteen carbons, 350 -N3, -NO2, -CN, -OH, -OG, 355 cycloalkyl of three to fifteen carbons, halo, -CO 2 R 6 -LιNR 7 R 8 -L2R9 360 alkyl of one to fifteen carbons, alkyl of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents independently selected from (=X), alkanoyloxy where the alkyl part is one to fifteen -301- 365 carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, alkoxy of one to fifteen carbons substituted with 1, 2, 3,4, or 5 halo substituents, 370 perfluoroalkoxy of one to fifteen carbons, -N 3 , -NO 2 , -CN, -OH, 375 provided that no two -OH groups are attached to the same carbon, -OG, cycloalkyl of three to fifteen carbons, halo, 380 -CO2R6, -LιNR 7 R 8 , and -L 2 R 9 , -L 2 -heterocycle, and -L 2 -heterocycle where the heterocycle is substituted 385 with 1, 2, 3, or 4 substituents independently selected from alkyl of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, 390 alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, -NRχC(O)NRγR z , -C(=NRX)RγR z , 395 -NO2, and -N 3 , (ii) (=X) (iii) alkanoyloxy where the alkyl part is one to fifteen carbons, -302- (iv) alkoxy of one to fifteen carbons, 400 (v) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo, (vi) thioalkoxy of one to fifteen carbons, (vii) perfluoroalkoxy of one to fifteen carbons, (viii) -N 3 , 405 (ix) -NO2, (x) -CN, (xi) -OH, provided that no two -OH groups are attached to the same carbon, 410 (xii) -OG, (xiii) cycloalkyl of three to fifteen carbons, (xiv) halo, (xv) -CO 2 R 6 , (xvi) -L1NR 7 R8, 415 (xvii) perfluoroalkyl of one to fifteen carbons, (xviii) -L2-heterocycle, and (xix) -L2-heterocycle where the heterocycle is substituted with 1, 2, 3, or 4 substituents independently selected from (=X), 420 alkanoyl where the alkyl part is one to fifteen carbons, alkanoyloxy where the alkyl part is one to fifteen carbons, alkoxy of one to fifteen carbons, alkoxy of one to fifteen carbons substituted with 1, 2, 3, 425 4, or 5 substituents selected from the group consisting of halo , thioalkoxy of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, perfluoroalkoxy of one to fifteen carbons, 430 -N 3 , -NO2, -CN, -303- -OH, provided that no two -OH groups are attached to the 435 same carbon, -OG, cycloalkyl of three to fifteen carbons, halo, -CO 2 R6, 440 -L 1 NR7R8, and -L 2 R 9 , (d) cycloalkyl of three to twelve carbons, (e) cycloalkenyl of four to twelve carbons, provided that a carbon of a carbon-carbon-double bond is not attached 445 directly to L when L 3 is other than a covalent bond where (d) and (e) can be optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, (ii) aryl, 450 (iii) alkoxy of one to fifteen carbons, (iv) thioalkoxy of one to fifteen carbons, (v) halo, (vi) -OH, provided that no two -OH groups are attached to the same 455 carbon, (vii) oxo, (viii) perfluoroalkyl, (ix) heterocycle, and (x) heterocycle substituted with 1, 2, 3, 4, or 5 substituents 460 independently selected from alkyl of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, 465 halo, -NO2, and -304- -N 3 , R, R A\Z Rc (f) R E provided that when Ri and R 3 are both perfluoroalkyl of one carbon, Z 470 is carbon, R2 is hydrogen, Q is phenyl that is 4-substituted by E relative to the position of attachment of the pyrazole ring to the phenyl group, R 4 and R5 are hydrogen, E is -L 3 -B, L 3 is -N(R7)C(X)-, R7 is hydrogen, X is oxygen, and R , RB > R D > and RE are hydrogen, Re is other than chloro, and 475 (g) heterocycle where the heterocycle can be optionally substituted with 1, 2, 3, or 4 substituents independently selected from (i) (=X), (ii) alkanoyl where the alkyl part is one to fifteen carbons, (iii) alkanoyloxy where the alkyl part is one to fifteen 480 carbons, (iv) alkoxy of one to fifteen carbons, (v) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo, 485 (vi) halo , (vii) thioalkoxy of one to fifteen carbons, (viii) perfluoroalkyl of one to fifteen carbons, (ix) perfluoroalkoxy of one to fifteen carbons, (x) -N 3 , 490 (xi) -NO 2 , (xii) -CN, (xiii) -OH, provided that no two -OH groups are attached to the same carbon, 495 (xiv) -OG, (xv) cycloalkyl of three to fifteen carbons, (xvi) halo, -305- (xvii) -CO 2 R6, (xviii) alkyl optionally substituted with -OH, 500 (xix) -L 1 NR7R8, and (xx) -L 2 R9, and 13 )^Rl4 (2) where Ri 3 and Ri 4 are independently selected from (a) hydrogen, (b) alkyl of one to fifteen carbons, 505 (c) alkenyl of three to fifteen carbons in the E or Z configuration, provided that a carbon of a carbon-carbon double bond is not attached directly to the C(=O) group, (d) alkynyl of three to fifteen carbons, provided that a a carbon-carbon triple bond is not directly attached to 510 the C(=O) group where (b), (c), and (d) can be optionally substituted with 1, 2, 3, or 4 substituents independently selected from RB R D (i) RE (ϋ) (=X), 515 (iii) alkanoyloxy where the alkyl part is one to fifteen carbons, (iv) alkoxy of one to fifteen carbons, (v) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo, (vi) thioalkoxy of one to fifteen carbons, 520 (vii) perfluoroalkoxy of one to fifteen carbons, (viii) -N 3 , (ix) -NO2, (x) -CN, (xi) -OH, 525 provided that no two -OH groups are attached to the same carbon, -306- (xii) -OG, (xiii) cycloalkyl of three to fifteen carbons, (xiv) halo, (xv) -CO 2 R 6 , 530 (xvi) -LιNR 7 R 8 , (xvii) perfluoroalkyl of one to fifteen carbons, (xviii) -L 2 -heterocycle, and (xix) -L 2 -heterocycle where the heterocycle is substituted with 1, 2, 3, or 4 substituents independently selected from 535 (=X), alkanoyl where the alkyl part is one to fifteen carbons, alkanoyloxy where the alkyl part is one to fifteen carbons, alkoxy of one to fifteen carbons, 540 alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo, thioalkoxy of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, 545 perfluoroalkoxy of one to fifteen carbons, -N 3 , -NO2, -CN, -OH, 550 provided that no two -OH groups are attached to the same carbon, -OG, cycloalkyl of three to fifteen carbons, halo, 555 -CO 2 R6, -L1NR7R8, -L 2 R 9 , (e) cycloalkyl of three to twelve carbons, (f) cycloalkenyl of four to twelve carbons, -307- 560 provided that a carbon of a carbon-carbon double bond is not attached directly to the C(=O) group where (e) and (f) can be optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from (i) alkyl of one to fifteen carbons, 565 (ii) aryl, (iii) alkoxy of one to fifteen carbons, (iv) thioalkoxy of one to fifteen carbons, (v) halo, (vi) -OH, 570 provided that no two -OH groups are attached to the same carbon, (vii) heterocycle, and (viii) heterocycle substituted with 1, 2, 3, 4, or 5 substituents independently selected from 575 alkyl of one to fifteen carbons, perfluoroalkyl of one to fifteen carbons, alkoxy of one to fifteen carbons, thioalkoxy of one to fifteen carbons, halo, 580 -NO 2 , and -N 3 , (g) heterocycle, and (h) heterocycle substituted with 1, 2, 3, or 4 substituents independently selected from 585 (i) (=X), (ii) alkanoyl where the alkyl part is one to fifteen carbons, (iii) alkanoyloxy where the alkyl part is one to fifteen carbons, (iv) alkoxy of one to fifteen carbons, 590 (v) alkoxy of one to fifteen carbons substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halo, (vi) thioalkoxy of one to fifteen carbons, -308- (vii) perfluoroalkyl of one to fifteen carbons, 595 (viii) perfluoroalkoxy of one to fifteen carbons, (ix) -N3, (x) -NO2, (xi) -CN, (xii) -OH, 600 provided that no two -OH groups are attached to the same carbon, (xiii) -OG, (xiv) cycloalkyl of three to fifteen carbons, (xv) halo, 605 (xvi) -CO 2 R 6 , (xvii) -LιNR 7 R 8 , (xviii) -L2R9, rovided that at least one of Rι 3 and R 14 is other than hydrogen, or 1 3 and R 1 4 together with the nitrogen to which they are attached form a ring 610 selected from (a) succinimidyl, (b) maleimidyl, (c) glutarimidyl, (d) phthalimidyl, 615 (e) naphthalimidyl, 0 H 3 C\ A N— ω o o H 3G^ A I N— H 3 C ^ (g) O H ^A κ H 3 c ^ r H 3 C 0 (h) -309- (i) 620 (j) (k) (1) H and N I A (m) CH where (a)-(m) can be optionally substituted with 1, 2, 3, 4, or 5 substituents 625 selected from halo and -L 2 R 9 . -310-

Inventors: BA MAUNG NWE Y, BASHA ANWER, DJURIC STEVAN W, GUBBINS EARL J, LULY JAY R, MADAR DAVID J, SCIOTTI RICHARD J, TU NOAH P, WAGENAAR FRANK L, WARRIOR USHA, WIEDEMAN PAUL E, ZHOU XUN, BA MAUNG, NWE, Y., BASHA, ANWER, DJURIC, STEVAN, W., GUBBINS, EARL, J., LULY, JAY, R., MADAR, DAVID, J., SCIOTTI, RICHARD, J., TU, NOAH, P., WAGENAAR, FRANK, L., WARRIOR, USHA, WIEDEMAN, PAUL, E., ZHOU, XUN
Applicants: ABBOTT LAB, ABBOTT LABORATORIES
Application year: 1999
Main classification: C07D231
IPC codes: A61K31, A61P17, A61P29, A61P37, A61P43, C07D231, C07D401, C07D403, C07D405, C07D409, C07D413, C07D417, C07D495