LV10264B - Diaryl- or diheteroaryl-substituted anti-aids compounds - Google Patents

Abstract

The innovation relates to diaryl- or diheteroaryl-substituted compositions that can be used to treat people infected with human immunodeficiency virus (HIV). The innovation includes some common anti-AIDS piperazin compositions and method of treatment of HIV infected people using indoles and anti AIDS amines.

Description

-1- LV 10264 DIAROMATIC SUBSTTTUTED ANTĪ-AIDS COMPOUNDS BACKGROUND OF THE INVENTION 1. Field of the Invention

The diaromatic substituted compounds flll), the and-AIDS piperazines (IV), the 5 indoles (V) and the anti-AIDS amines (X) of the invention are useful in the treatment of individuāls who are HIV positive whether or not they show AIDS symptoms at the present time. 2. Pescription of the Related Art

International Publication No. WO 87/01797 discloses compounds which can be 10 visualized as steroid-piperazine-[substituted aromatic] or steroid-piperazine-fsubstituted heteroaromatic]. The steroid and piperazine being "connected" via the Cl7,.side-chain of the steroid.

International Publication No. WO 88/08424 disclosed compounds which can be visualized as aromatic-connector-piperazine-fsubstituted aromatic] or aromatic-connector-15 piperazine-[substituted heteroaromatic], in particular see the compounds of formulas (I) and (ΙΠ). None of those compounds were disclosed as having the utility set forth in this invention. In U.S. Patent application 07/425,726, filed 10-23-89, it was disclosed that the compounds of formula (I) of International Publication No. WO 88/08424 were useful againstAIDS. 20 US Patent 4,728,650 (Kuraray I) discloses hydroxy-trolox compounds similar to the compounds of formula (ΠΙ) of International Publication No. WO 88/08424. WO 87/05020 (Kuraray Π) discloses additional compounds of the same type.

An estimated one to one and one-half million people in the United States are infected with a human retrovirus, the human immunodeficiency vims type I (ΗΓ/-1) 25 which is the etiological aģent of acquired immunodeficiency syndrome, AIDS, see Science, 661-662 (1986). Of those infected, an esdmated two hundred and fifty thousands people will develop AIDS in the next five years, see Science, 1352-1357 (1985). On March 20, 1987, the FDA approved the use of the compound, AZT (zidovudine), to trcat AIDS padents with a recent initial episode of pneumocysds carinii 30 pneumonia, AIDS padents with condidons other than pneumocystis carinii pneumonia or padents infected with the virus with an absolute CD4 lymphocyte count of less than 200/mm1 in the peripheral blood. AZT is a known inhibitor of virai revcrse transcript-ase, an enzyme necessary for human immunodeficiency vims replicadon. -2- U.S. Patent 4,724,232 claims a method of treating humāns having acquired immunodeficiency syndrome utilizing 3’-azido-3’-deoxy-thymidine (azidothymidine, AZT).

It is known in the art that certain antibiotics and polyanionic dyes inhibit retrovirus reverse transcriptase.

Many publications have reported the ability of various sulfated compounds to inhibit vīrus replicadon, including HIV.

Nature 343, 470 (1990) and Science 250, 1411 (1990) discloses potent benzodiazepin type reverse transcriptase inhibitors. The compounds of the present invention are not benzodiazepin type compounds. US Patent 3,188,313 discloses compounds of the general formula [substituted indol-2-yl]-(CH2)B-[piperazinyl type]-[pyridinyl/pyrimidinyl].

The diaromatic substituted compounds (III) of the present invention differ from the prior art compounds in that they require the substitution on -φ to be a group di'fferent than that of the group in US Patent 3,188,313. US Patent 3,472,855 and 3,562,278 disclose 3-indolinyl compounds which are Useful as psychomotor depressants. The 2-indolinyl compounds of the present invention are useful for a totally different purpose, inhibition of HIV-RT and treatment of AIDS. US Patent 3,362,956 discloses compounds of the general formula [3-quinolylHCH2)B-[piperazinyl type]-[pyridinyl/phenyl],

The diaromatic substituted compounds (III) of-the present invention differ from the prior art compounds in that they do not include 3-quinolyl type compounds. US Patent 3,472,854 discloses compounds of the general formula [2-benzimidazolyl)-(CH2)B-[piperazinyl type]-[pyridinyl/phenyl].

The diaromatic substituted compounds (III) of the present invention differ from the prior art compounds in that they do not have a metbylene linker, -(CHj),-, when the heteroaryl group is 2-benzimidazolyl. US Patent 3,491,098 discloses compounds of the general formula [4(5)-imidazoIylHCHj),-[piperazinyl type]-[pyridinyl/phenyl].

The diaromatic substituted compounds (III) of the present invention differ from the prior art compounds in that they require the substitution on -φ to be a group different than that of the group in the US Patent 3,491,098. US Patent 3,511,841 discloses compounds of the general formula -3- LV 10264 [azaindolyl]-(CH2V[piperazinyl type]-[pyridinyl/phenyl] [azaindolyl]-CO-[piperazinyl type]-[pyridinyl/phenyl]

The diaromatic substituted compounds (III) of the present invention differ from the prior art compounds in that they require the substitiition on -φ to be a group different than that 5 of the group in US Patent 3,188,313. US Patent 4,302,589 discloses 3-indolinyl compounds with a methyl group at the C2 position of the indole and an ethyl bridge between the indole and piperazine which are useful as anti-psychotics. The 2-indolinyI compounds of the present invention are useful for a totally different purpose, inhibition of HIV-RT and treatment of AIDS. 10 European patent publication 345,808 discloses 3-indolinyl-piperazinyl-[substituted 2-pyridinyl] compounds (example 66) which are useful as anti-depressants. The 2-indoIinyl compounds of the present invention are useful for a totally different purpose, inhibition of HTV-RT and treatment of AIDS.

There are a number of other chemically unrelated compounds vvhich have been 15 reported to inhibit HIV and/or be useful in the treatment of AIDS.

The anti-AIDS piperazines (IV) of the present invention are a few particular piperazines previously generically disclosed in Intemationai Publication No. WO 88/-08424.

The indoles compounds (V) of the present invention have been previously 20 generically disclosed in Intemationai Publication No. WO 88/08424, see the bicyclic compounds of formula (III) therein.

SUMMARV OF INVENTION

Disclosed is a diaromatic substituted compound of formula (III) where 25

R? [Ar/l/Heteroar/lļ-RpZ

m where R, is -CH2-, -CO-, -CO-CH,-, 30 5 -4- where Z is where -SOr. -CH-CH-CO-;

(Z-I) 10 (I) R2 is =0 or R2.,;R2.2 where one of R2., and R2.2 is -H and the other of R2., and R2.j is -H or -CHJf

Rj is =0 or Rj-l‘Rj-2 where one of Ki and Rw is -H and the other of R3.1 and Rj.3 is -H or -CH3, R< is R*.,:R«.j and R5 is R^R» where one of R*., and R^ is -H and the other 15 of R^ and R^ is *H or -CH3l where one of Rj., and RM is -H and the other of R5., and Rj.j is -H or -CH3, (Π) R, is R«.3:Rm and R3 is Rj.3:R3-< where one of R«.3 and Rm and one of R^ and Rw are taken together to form -CH2- and the other of R^ and RM, and R3.3 and RJ4 are -H, R2 and R3 are 20 (III) R2 is R2.3:RM and R5 is RW:RW where one of R2.j and Rw and one of R5.j and Rw are taken together to form -CH2-CH2- and the other of R2.5 and Rw, and R5.5 and Rw are -H, and R3 and R4 are (TV) R3 is R^jtR^ and R, is R^jiR^ where one of Rj.5 and Rw and one of R^ and R^ are taken together to form -CH2-CH2- and the other of R^j and Rw, and R^ and 25 R^ are -H, and R2 and R3 are (Z-II) -VKCH^-ZHCHjU-Vr where riu is 1 thm 5, nM is 1 thru 5, Y, is -0-, -S-, -N(Y,.0- where Y,_, is C,-C4 alkyl, 'C(Y1.2)(Y,.3) where Yw and Y',.3 are the same or different and are -H or

Cj-C4 alkyl, Y2 is -O, -S-, 30 LV 10264 -N(Ym)- where Y2., is C,-C4 alkyl, -C(Ym)(Ym> where Y2.2 and Y20 are the same or different and are -H or C,-C4 alkyl, Zļ is nothing (a bond), -0-, -S-, 5 •N(2^.,)- where Zj., is -H or C,-C4 alkyl, -0*0-, *C(2where Zj.2 and Z*, are the same or different and are -H or

Cj-C4 aJkyl, cis and trans -0^.3)=0(2^.3)- where Zj.2 and are the same or 10 different and are -H or C,-C4 alkyl, with the provisos (1) that when Y, is -0-, -S- or *N(Y,.i)·, then nn is 1 only when Zj is nothing (a bond), -C*C-, -CĪZ^Z^)- or -£(Zi.d=0(2ļ.j)· and (2) that when Y2 is -0-, -S- or -N^j.,)-, then n26 is 1 only when Zj is nothing (a bond), -C = C-, -C(Z2.2)(Z2.3)- or -C(Z2.2)=C(Z2.J)-, 15

(Z-III) where n,2 is 1 or 2 and nl3 is 1 or 2, 20

(Z-IV) 25 where n,2 and n13 are as defined above,

(Z-V) where Y3 is -Ν(ΥΜ)- where YM is C,-C4 alkyl and nl2 and nl3 are as defined above; R« is -N=, 30 -6- -CH=, -N(0)=, R7 is -COO-R7.1, where R7.M is as defined above, -CO-N(R7.3)(R7»«) where R7.3 and Rw are the same or different and are -H or C,-C6 alkyl, -N(R7.j)(R74) where R7.5 is C,-Cealkyl, ‘C(R7.|j)(R7.i6)-(R7.i7) where R7.,j and R7.,6 are the same or different and are -H or C,-Cj aikyl and where R7.l7 is C2-Cj alkenyl containing 1 or 2 double bonds or C2-Cj alkynyl containing 1 triple bond, -CHj-CHj-OH, -CHj-CHj-CHj-OH, . -CH(CHj)CH2-0-CH„ *CH(CHj)CH2-OH, -CHj-CFj, •CH2*cyclopropyl, •CHj-CHjF, -CHj-CHj-CeN, •C’R7.„*(CH2)n,4-C'H2 where R7.„ is -H or -CHJt nM is 1 thru 5 and the carbon atoms marked with an asterisk 0 are bonded to each other to resulting in the formation of a ring, -(ΟΗ^η,-Ν^.·;)^.!) where n, is 2 or 3 and where R7.7 and R74 are the same or different and are -H or C,-C4 alkyl, and where R7.7 and R74 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-moipholinyl, 1-aziridinyl, and where R74 is *H, C,-C4 alkyl, *C(R7.ļj)(R7.ļj)”(R7.|7) where R7.u> R7.ie <tnd R7.i7 āre as defined above, -CHrCHrOH, -CH2-CH2-CH2-OH, •CH2CFj, -7- LV 10264 -CH2-CH2F, -CH2-CH2-C«N, or where R7.j and R^ are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, 1-5 piperazinyl, N-morpholinyl or l-aziridinyl, -(CH^-NCR,.,)^.,^ where n* is 1 or 2 and where R7.9 and R7.l0 are the same or different and are -H or C,-C4 alkyl, and where R7.9 and R7.l0 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinylf l-piperidinyl, l-piperazinyl or N*morpholinyl, 10 R, is -N», -CRn= where R,., is -H, -F, -Cl, -Br, -CF3, •NOj, -COCFj, . Cj-C* alkyl, C^Cj alkylthio, 15 -OH, -ORj.7 where R,.2 is C,-C6 alkyl, -Φ, -CO-Rw where R,.3 is C,-C6 alkyl or ·φ, -NH(Rm) where RM is C,-C6 alkyl, 20 -C(Rj.7)(R».»)-(R|.9) where Rj.7 and Rw are the same or different and are -H or C,-C3 alkyl and wh'ere RM is C2-C5 alkenyl containing 1 or 2 double bonds or C2-C5 alkynyl containing 1 triple bond, -NR^j-CO-R,^ where R,.j is -H or Ci*C6 alkyl and Rw is -H, C,-C4 alkyl or C,-C3 alkoxy; 25 R, is -N-,

«I -CR*,= where R,., is -H, -F, -Cl, -Br, -NOj, -COCFj, C,-C6 alkyl, C,-Cj alkylthio, 30 -OH, -O-Rm where R^j is Ci*C6 alkyl, -Φ, -CO-R*.3 where R*.3 is C3-Ce alkyl or -Φ, -N(R*J(R*5) where R^ and R*.j are the same or different and are -8- *Η,

Cj-C6 alkyl, -C^OV^-OVio) where and R9.9 are the same or different and are *H or Cj-Cj alkyl and where is C2-Cf alkenyl containing 1 or 2 double bonds or C2-Cs alkynyl containing 1 triple bond, R*.* and R^ are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, 1-piperidinyl, l-piperazinyl or N-morpholinyl, -NR^-CO-R^ where R^ is -H or Ci-C6 alkyl and R,.7 is -H, Ci*C6 alkyl or Cj-Cj a!koxy; RJ0is-N=, -CRl0.,= where RJ0.i is -H, -F, -Cl, -Br, -CF3, -NOj, -COCFj, C,-C6 alkyl, Cļ*C3 alkylthio, -OH, -O-Rjo.2 where RIM is C,-C6 alkyl, -Φ, -C0-R1W where R10.3 is C,- C6 alkyl or -Φ, -N(Rl0J(R|o.j) where Rl(M and R,w are the same or different and are -H, C,-C6 alkyl, where Rl0.t and Rl0.9 are the same or different and are -H or Cj-C3 alkyl and where R^o is C2-Cj alkenyl containing 1 or 2 double bonds or C2-C3 alkynyl containing 1 triple bond, -NRiw-CO-Rj0.7 where Rlw is -H or C,*C6 alkyl and Rl0.7 is -H, Ci-C6 alkyl or Cj-C3 alkoxy; with the proviso that not more than two of R*, R», R9 and Rw are -N»; Aryl/Heteroaryl is a substituent selected from the group of substituents of formula

(1) (1) -9- LV 10264 where Xx is -H, Cj-C* or n-alkyl, X2 is -H, Cj*C6 or n-alkyl, X} is C,-C6 alkyl, -CO-XM where X3., is C,-C4 alkyl or -Φ, 5 -CHj-Φ, *; ... of formula (2)

(2) where X< and X3 are the same or different and are -H, C,-C4 alkyl, 15 where ns is 2 or 3 and where XM and X*.2 are the same or different and are -H or C,-C4 alkyl or where and Χ^ are taken together » with the attached nitrogen atom to form a heterocyclic ring selected from the group consisdng of l-pyrrolidinyl, l'piperidinyl, l*piperazinyl or N-morpholinyl, and where X4 and Xs are taken together with the attached nitrogen atom 20 to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl> 1-piperidinyl, l-piperazinyl or N-morpholinyI, and where Xj and X2 are as defined above, with the proviso that both Χ4 and X} are not both -H; ... of formula (3)

where X« is -H,

CrCi alkyl, -10- *F, -Cl, Br, -OH, -O-CH,-*, -O-CFj, -O-CHj-COO^h where X±x< is -H, C,-C6 alkyl, -φ, -CH,-0, -CHO, 5 C^Cj alkoxy, C,-C3 alkylthio, -O-CO*^, where X*.j is -H, C,-C4 alkyl or -O-SO^mj where X«.,j is CrC4 alkyl, -COO-Χ^υ where Xe.,3 is -H, C,-C4 alkyl, -φ or -CH,-φ, 10 -C«N, -NO,, -N„ -NX4.10X4.il where XM0 and are the same or different and are -H or C,-C, alkyl or where Χ^,ο and Xe.„ are taken together with the attached nitrogen atom to form a heterOcyclic ring selected from the group consisting of l-pyrrolidinyl, 1-15 piperidinyl, l-piperazinyl, N-morphoIinyl or .l-aziridinyl, -N^^CH^-NpCi.,)^) where n, is 2 thru 5, Χ4., is -H or Cw alkyl, Χ*.3 is -H or CH alkyl, Xw is -H or CM alkyl, or where X4.3 and Xju are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinylt l-piperidinyl, l-piperazinyl, N-morpholinyl 20 or l-aziridinyl, -O-CO-iCH^ej-COOH, where n3 is as defined above, -O-fCH^^-N(X4.3)(X^) where n3, X4.3 and X^ are as defined above, -(CH^-OH, where n,4 is 1 thru 5, 25 -(CH^-NpCj.jJpC^ where 1¾ is 1 thru 5 and Χ^ and Xw are the same or different and are -H, Cj-C4 alkyl or where Χ4_3 and X** are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, -NH-SO,-X4.7 where Χ4.7 is C,-C4 alkyl, C3-C7 cycloalkyl, -φ or 30 -CH,-φ, - -N=C(Xw)-N(X<,7)(X6.i) where (a) Χ4., is C,-C4 alkyl, C3-C; cycloalkyl or -φ and where Χ+4 and X*.7 are as defined above, -11- LV 10264 (b) Χ4.7 and XM are taken togelher with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinylt (c) XM and Χ^ are taken together with the attached 5 nitrogen atom to form a heterocyciic ring selected from the group consisting of l- pyrrolidinyl or l-piperidinyl, -ΝΧ^-ΟΟ-Χ*., where Χ^ is -H, alkyl or -Φ and where X^ is as defined above, -O-prodrug where prodrug is 10 -ΡΟ2-Ο·03ΐίοη+, -CO-CHj-CO-NH-CHj-SOj-O* cation*. -CO-fCHj^-Rj, where n21 is 1-7 and Rj, is -COO* cation+, -NRM.ļRjj.2 where Rj,., and R31.2 are the same or different and are -H or C,-C3 alkyl, -N+RJ1.,Rjl.2RJ,.jhalide* where R3M, Rj,.2 and R31.3 are the same or different and are -H 15 or Ci-Cj alkyl, and where halide is -C1 or -Br; -CO-CH(amino acid)-NH2 where amino acid is -H, -CHj, -CHCCH^, -CH2-CH(CH3)2, -CH2-OH, -CH(OH)(CH3), -CHH>, -CH2-[p-hydroxy-phenyl], -CH2-[3-indolyl], -CHj-S-S-CH^CHCNHJ-COOH, -CH2-SH, -CH2CH2-S-CH3, -CH2-COOH, -CH2-CO-NH2, -CH2-CH2-COOH, -CH2-CH2-CO-NH2i -CHr[2-20 HISTIDYL], -(CHjVNH-CfNHJ-NHj, -(CH^-NHj, -CH2-CH2-CH(OH)-CH2-NH2, -(CH^-NHj, -(CH^j-NH-CO-NHj -CH2CH2-OH, -CO-CH=CH-C0-0* cation+, -CO-N’-CH=CH-N=CH* where the atoms marked with an asterisk 0 are bonded to each other resulting in the formation of a ring, 25 -CO-C*=CKCHj^-NHJ-CH=CH-CH=CH* where n„ is 1 or 2 and vvhere the atoms marked vvith -an asterisk 0 are bonded to each other resulting in the formation of a ring, -CO-C*=CH-CH=C(-NR32)-CH=CH* where RJ2 is -H or C,-Cj alkyl and where the atoms marked with an asterisk 0 are bonded to each other 30 resulting in the formation of a ring, . -CO-iCH^-CO-O-tC^A sugarsj, -C0-0-CH(CH2-0-C0-R33)2 where the R33’s are the same or different and are Cj-Cu, -12- -CO-(CH^6-CO-N(CH,)-CHrCH2-SO,*cation+, -CH2-0-C0-(CH2)ll21-NRj1.,RJ,.2 where n2l, Rjw and R51.2 are as defined above, -CO-NH-CeH4-Rjj where R5J is -H or C,-Cj alkyl, -N02, -NRjj.jRjj.j where Rj,., and RS1.2 are as defined above, -NXM*prodrug where Xw and prodrug are as defined above except that prodrug is not -P02-0·, n2 is 1 thru 3, the X4’s can be the same or can be different and where when n2 is 2 and the two Xj groups are ortho to each other they can be taken together to form -0-CH2-0-; with the proviso that if n2 is 2 or 3, on!y one of the ^’s can be a prodrug, ... of formula (4)

(4) vvhere Q, is -NXn.where XtJ is -H, -SO2-ψ, -S02-CHJf -CO-Xu.t where Xu.j is C|-C4 alkyl, -CF3 or -φ\

Qj is -N= provided Rt is not -CH2-, -CXi2=s where XJ2 is -COO-X|m where X,2.i is -H or Cj-C4 alkyl, -CO-N(X,2.2)(X,2.3) where X,2.2 and X,2.3 are the same or different and are -H, C,-C4 alkyl or where X,2.2 and X,2.3 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, -CO-COO-X12.j where Xm is as defined above, C,-Cj alkyl, -CO-0, -CO-Xi2.j where X12.t is as defined above, -CO-CO-NpCu.^^uoj vvhere X,2.2 and Xl2.3 are as defined above, -(CH^-OH vvhere na is 1 or 2, and vvhere X< and n2 are as defined above, ... of formula (6) (6) LV 10264

. of formula (7) 5

(χ$)θ7 (7) 10 where ^ is a single or double bond, XM is -H, -O-CHj-ψ, -O-CFj, -O-CH2-COOR,4.,0 where R14.10 is -H. C,-C4 alkyl, -Φ or -CHj-ψ, C,-C6 alkyl, 15 -F, -Cl, Br, -0-S0j-X,4.„ where Xj4.jļ is Ci*C4 alkyl, -ON, -CHO, •(CHjJrfj-OH where ηΜ is 1 thru 5, 20 -NOj, -NHj. -NJt -NH-CHj-Ψ, -NH-S02-Xl4., where Xl4., is C,-C6 alkyl, C3-C7 cycloalkyl or -φ, -ΝΧ,^ΟΗ^-ΝζΧ^ίΧ^) where n3 is 2 thru 5, X14.2 is -H or CM alkyl, X14.j is -H or CM alkyl, X144 is -H or CM alkyl, or where X14.j and Xl4_« are taken 25 together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, -NX14.,jX14.14 where Xl4.,j and’X14.,4 are the same or different and are -H or CpCj alkyl or where Xļ4.,j and X,4.,4 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, 1* 30 piperidinyl, l-piperazinyl or N-moipholinyl, -(Οί^-ΝζΧ,^χΧ,^ where n« is 1 thru 5 and Xl4.j and X,M are the same or different and are -H, C,-C4 alkyl or where XI4.j and X14^ arc taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting -14- of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-moipholinyl, -N=C(X1m)-N(X14.7)(X14.,) where i (a) Xļ4.7 and X1M are CrC6 alkyl, Cj-C^ cycloalkyl or -φ, where Xj4_4 is as defined above, 5 (b) X|*.7 and X,4., are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, 1-piperidinyl, l-piperazinyl or N-morphoIinyl, (c) Xl+4 and XJ4.7 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl or 10 l-piperidinyl, -C0-0-X14.7 where Xl4.7 is as defmed above, -CO-N(X14.7)(X14.0 where Xl4.7 and X,w are as defined above, -NCXI4.^-CO-Xl4.9 where XI4.j is -H, Ci-C4 alkyl or -φ where X14.2 is defined above, 15 -N(X14.2)*prodrug, where prodrug is as defined above except that it is not -P02-0\ and when X14_2 is as defmed above, rh is 0 thru 2,

Xt and Q, are as defined above; ... of formula (8) 20 *22

(8) 25 vvhere X2J is -H, C,-C4 alkyl, -CO-(C,-C4 alkyl), -CH2-φ, -CO-φ or -prodrug where prodrug is as defined above,

Xs, Χν and XM are the same or different and are -F, -Cl, Br, 30 -OH, -O-CHj-φ, -O-CFj, -0-CH2-C00H, C,-C, alkoxy, C,-Cj alkylthio, -0-C0-X22., where Xa., is -H, C,-C4 alkyl or -φ, -15- LV 10264 -NO,, -NH„ -N„ -ΟΝ, -NXn.2(CH2)o9-N(X22.j)(X224) where n, is 2 thru 5, Xa.2 is -H or C,-C4 alkyl, X22.3 is *H or Cj-C4 alkyl, X224 is -H or C|-C4 alkyl, and where Χ^ and Xa4 are 5 taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of i-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyI, «O-CO-iCH^nj-COOH, where n9 is as defined above, -0-(CH2)b9-N(X22.j)(X22J where n9, X22.3 and Xa^ are as defined above, where n,0 is 1 thru 5 and Xa.j and XB^ are the 10 same or different and are -H, C,-C4 alkyl and where Xn.j and ΧΏ4 are taken together with the attached nitrogen atom to form a heterocyclic ring selected ,.from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, •ΝίΧ^ΧΧ».!) where Χη.7 and XH.t are C,-C6 alkyl, C3-C7 cycloalkyl or 15 and where any adjacent two of -0-X2l, X», ΧΒ or XM are taken together to form a methylenedioxy group (*0*CH2-0-),

Qi and ^ are as defined above; ... of formula (9) 20

(9) xil 25 vvhere X,0 is -H, -F, -C1 or -Br,

Qj is -CH= or Q2 where (¾ is as defined above, X* and Xu are as defined above; ... of formula (10)

-16- where X<, X„ and Qj are as defmed above; ... of formula (11)

where X7 is -H, -SO2-φ, -S02-CHj, -CO-X7., where X7., is C,-C4 alkyl or -ψ, X, is -H, Ci-C6 alkyl, -CH2-4>, -S02-4>, -S02-CH3, -CO-Xw where XM is alkyl or -ψ, uu is as defmed above; ... of formula (15)

%

hi where (¾ and X„ are as defmed above; ... of formula (16)

where (¾ and X„ are as defmed above; of formula (17) • 1 · LV 10264

(17) where (¾ and Xn are as defined above; ... of formula (18)

(18) 15 where Q, and Xu are as defined above; ... of formula (19)

... of formula (20) (19)

Ml where Qj and Xu are as defined above; of formula (21) (20) 30 (21) -18- <ς6)·7

5 where Q;, X6 and n7 are as defined above; with the proviso that one of R7.s or Rw must be -H when R« is not -N=, enantiomers, pharmaceutically acceptable salts, hydrates and solvates thereof. t

Also disclosed are anti-AIDS piperazines (IV) selected from the group consisting of compounds of EXAMPLES 1, 3-5, 7, 12, 16, 26, 28, 37, 38,42, 45, 64, 77,78, 80, 10 107,116,135,136 and 145-148 enantiomers, pharmaceutically acceptable salts, hydrates and solvates thereof.

Further disclosed is a method of treating an individual infected with the human immunodeficiency virus (HIV) which comprises administering an effective amount of a indole of formula (V) 15

(V) 20 where R,A is -CH2-, -CO-, ι -SQr, -CH=CH-CO-, -CO-CH2-, 25 where R« is -N=, -CH=, -N(0)=; R7a is -S-R7a., where R7A., is C,-C6 alkyl, * 30 *0-R7a.2 where R7A.2 is C,-Q alkyl, ”C(R7a.ij)(R7a.i4)"(I^7a-i7) where R7A.u and R7A.ie are the same or different and are -H or C,-C2 alkyl and where R7A.I7 is C^-Cj alkenyl containing 1 or 2 -19- LV 10264 double bonds or C2-C3 alkynyl containing 1 triple bond, -CO*R7A.„ where R7A.U is -H, C2-C4 alkyl, C2-C6 alkenyl containing 1 or 2 double bonds, C2-C6 alkynyl containing 1 triple bond, -ch,-*; -Φ optionally substituted with 1 thru 3 -CF3, C,-C4 alkyl, 10 -OH,

Cj-Cj alkylthio, -0*C0-R7a.,2 where R7A.,2 is C,-C6 alkyl or ·φ, -F, -Cl, -Br, -CO-CFj, 15 -NO,, -N(R7a.,j)(R7a.m) where R7A.,3 and R7a.,4 are the same or different and are -H, C,-Cj alkyl and where R7A.,3 and R7A.,4 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrroIidinyI, l-piperidinyl, l-piperazinyl or N-morpholinyl, 20 -COO-R7a.„ vvhere R7A.„ is as defined above, -CO-N(R7a.3)(R7aJ where R7A.3 and R7iM are the same or different and are -H or C,-C6 alkyl, I· -N(R7a.5)(R7aJ where R7a.j is.· C,-C4 alkyl, 25 -C(R7A.u)(R7A.w)-(R7A.»7)where RM,ts,R7A.l( and R7a.,7 are as defined above, -CH2-CH2-OH, -ch2-ch2-ch2-oh, -CH(CH3)CH2-0-CH3, -CH,-cyclopropyl, -CH(CH3)CH2-OH, -ch2-cf3, -ch2-ch2f, 30 -20- -CH2-CH2-C«N, -C*H-(CH2)o14-C’H2 where n,4 is 1 thru 5 and the carbon atoms marked with an asterisk (*) are bonded to each other to resulting in the formation of a ring, -(CH2)n,-K(R7A.7)(R7A.|) where n, is 2 or 3 and where R7a.7 and R7A. i are the same or different and are -H or C,-C4 alkyl, and where R7a.7 and R7a4 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl, N-morpholinyl, 1-aziridinyl, and where R7A_e is -H, Cļ-Cj alkyl, -C(R7A.li)(R7A.16)-(R7A.,7) where R7A.u, R7a.i6 and ^7a-j7 are as defined above, -CH2-CH2-OH, -ch2-ch2-ch2-oh, -ch2cf„ -CHj-CHjF, -CH2-CH2-C ss n, or where R7A.S and R7a< are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1 -pyrrolidiny 1, l-piperidinyl, 1-piperazinyl, N-morpholinyl or l-aziridinyl, -(CH^-NfR^fR^.,,,) where a» is 1 or 2 and where R7a.9 and R7a.|0 are the same or different and are -H or C|-C4 alkyl, and where R7A.9 and R7A.,0 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinylf l-piperazinyl or N-morpholinylf R, is -N=, -CRm= where Rw is -H, -F, -Cl, -Br, -CF„ -NOj. -COCFj,

CrC6 alkyl,

Cj-Cj alkylthio, -OH, -0-Rw where Rw is C,-C4 alkyl, ·φ, -CO-Rw where Rw is Ct-C4 alkyl or ·φ, -NHfRm) where RM is C,-Q alkyl, LV 10264 -2i- •C(R».7)(Ri.,)'(R|.9) where and Rw are the same or different and are -H or C,-C3 aikyl and where RM is C2*Cļ alkenyl containing 1 or 2 double bonds or C2-C5 alkynyl containing 1 triple bond, -NR».j-CO-R,^ where Rw is -H or C,-C4 alkyl and Rw is -H, C,-C6 aJkvI 5 or C,-C3 alkoxy; R? is -N= or -CR^., = where R*., is *H, -F, -Cl, -Br, -N02, -COCF3, C,-C4alkyl# C,-Cj alkylthio, -OH, 10 -0-R*.2 where R*.2 is C,-C4 aikyl, -Φ, -CO-R^j where R*3 is C,-C4 alkyl or -ψ, with the proviso that R*.2 is not alkyi when R7 is -OR7.2, -NOR^OVj) where R,^ and R9.J are the same or different and are -H, C,-C4 aikyl, ; -C(R9.*)CR^9)-(R».īo) where R*» and R*, are the same or different 15 and are -H or C,-Cj alkyl and where R*,„ is C2-C} alkenyl containing 1 or 2 double bonds or C2-C} alkynyl containing 1 triple bond, R^ and R9.J are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisdng of l-pyrrolidinyl, 1* piperidinyl, 1-piperazinyl or N-morpholinyl, 20 -NR^-CO-R*.·; where R^ is -H or C,-C4 alkyl and R*.? is -H, C,-C4 alkyl or Cļ-Cj alkoxy; R,0 is -N~ or -CRjcm” where Rl0., is -H, -F, *C1, -Br, -CF3, -NOj, -COCF,, C,-C4 alkyl,

Cj-Cj alkylthio, 25 -OH, -0-R1M where Rl0.2 is C,-C6 alkyl, -φ, ’CQ-Rm where Rīo.j is Cx-C6 alkyl or -Ψ, -N(R,(m)(Rio.j) where Rl(M and RIW are the same or different and are -H, C,-C4 aikyl, 30 -C(R|o.*)(Rio.»MRio.io) where R,„ and Rl0.9 are the same or different and are -H or C,-Cj alkyl and where R10.i0 is Cļ-Cļ alkenyl containing 1 or 2 double bonds or CVC5 alkynyl containing 1 triple bond, *NRio4"CO-Rio7 where R.« >s -H or C,-C6 aikyl and RJ0.7 is -H, C,-C4 -22- % where is a single or double bond; Q, is -NXn where X„ is -H, -S02-tf, -S02-CH3, -CQ-XU., where X,,., is C,-C4 alkyl, -CF3 or -φ\ Xj7 is -H or -CH,; 5 Xu is -H or -CH3; X„ is -H or -CH3; Xļo is -H, Cj-C4 alkyl, -CO*(C,-C4 alkyl), -CH2-φ, -CO-ψ or -prodrug; where Z and prodrug are as defined above; with the proviso that R, is not -CH2-when R17, R„ and R,9 are ali -CH3; and enantiomers, pharmaceudcally acceptable salts, 10 hydrates and solvates thereof. Additionally disclosed is a method of treating an individual infected with the human immunodeficiency virus (HIV) which comprises administering an effective amount of an anti-AIDS amine of formula (X) 15 20 where R|B is -CH2-, -CO-, where R* is -N=, -CH=, (X) [Aryl/Beteroaryl]-Rj3* 25 R7B is -CO-Rtb.11 where R7B.n is -H, C,-C6 alkyl, C2-C6 alkenyl containing 1 or 2 double bonds, „ C2-C6 alkynyl containing 1 triple bond, -CHj-0, •Φ optional!y substituted with 1 thru 3 *CF„ C,-C4 alkyl, -OH, C,-C3 alkylthio, •O-CO-R^n vvhere R^ is C,-C6 alkyl or -φ, 30 -23- LV 10264 -F, -Cl, -Br, -CO-CFj, •NO,, -N(R7B.i3)(R7b.,4) where R7B.,3 and R7B.M are the same or different and are -H, Cj-Cj alkyl and where R^jj and R7B.14 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, i-piperazinyl or N-morpholinyl, -S-Rtb., where R7B., is C,-C6 alkyl, -O-Rtm where R7B.2 is C,-C6 alkyl, -C(R7a.ļj)(R7B.u)*(R7g.i7) where R7b.u suid R7b-i6 «tr® Ή, or Cj-C3 alkyl and R7b-i7 is C2-Cj alkenyl containing 1 or 2 double bonds or Cj-Cj alkynyl containing 1 triple bond, R, is -N=, -CH= R, is -N=, -GH-Rl0is-N=,-CH= with the proviso that not more than two of R», R, and R,o are -N=; and where Z and [Aryl/Heteroaryl] are as defined above; enantiomers, pharmaceutically acceptable salts, hydrates and solvates thereof. DETAILED DESCRIPTION OF THE INVENTION The diaromatic substituted compounds 0Π) are generally and most often prepared by contaeting an aromatic-connector (I) with a substituted linker (II), see CHART A.

The aromatic-connectors (I) are either known to those skilled in the art or can readily be prepared from known compounds by methods well known to those skilled in the art. The aromatic-connector (I) is represented by [Aryl/Heteroaryl]-Ri*X13 where (Aryl/Heteroaryl] is an aromatic/heteroaromatic substituent (1)-(4), (6)-(11) and (15)-(21), R, is a connector and X,3 is a good leaving group, see CHART A. Those (Ar-y!/Heteroaryl] substituents which when coupled with a substituted linker (II) producē the novel diaromatic substituted compounds (III), the anti-AIDS piperazines (IV) and the indoles (V).

The anti-AIDS piperazines (IV) are particular piperazines previously generically disclosed in International Publication No. WO 88/08424. The indoles (V) are produced by coupling the indole fragment with the appropriate substituted linker (II). The anti-AIDS amines (X) are produced in a manner similar as for the production of the -24- diaromatic substituted compounds (III).

For the diaromatic substituted compounds (III), the indoles (V) and anti-AIDS amines (X), it is preferred that the connector, R„ is :CO-. It is preferred that Z be (Z-II) or (Z-III), it is more preferred that Z is (Z-III). It is preferred that n12 and n„ are both 1 (piperazine). When Z is (Z-IV) or (Z-V) and n,2 and n,3 are not the same, two enantiomeric compounds are produced. It is to be understood that the formula (III) for the diaromatic substituted compounds includes both enantiomers. When Z is (Z-I) it is preferred that R2, R3f R< and R3 are ali -H:-H. It is preferred that R* is either -N= or -CH = ; it is more preferred that R« is -N=. It is preferred that R7 is -N(R7.3)(R7^) where one of R7.j and R^ is -H and the other of R7.5 and RM is C,-C< alkyl; it is more preferred that C,-C< alkyl is -CH2-CH3, -CH(ČH3)2 or -C(CH3)3. It is preferred that R,, R, and Rl0 are -CH=. It is also preferred that both R« and R» are both -N=. It is preferred that (Aryl/Heteroaryl] is a substituent of formulas (2)-(4), (6)-(11) and (15)-(21); it is more preferred that [Aryl/Heteroaryl] is a substituent of formulas (4), (7)-(11), (15) and (21); it is more preferred that [Aryl/Heteroaryl] is a substituent of formulas (4), (7) and (8); it is most preferred that [Aryl/Heteroaryl] is (7). It is preferred that Q, is -NH-, that X* is -H, -F, -OCH3t -N(CH3)2 and -CH2-N(CH3)2. It is preferred that the diaromatic substituted compounds (III) is selected from the group of compounds of EXAMPLES 11, 17,19-25, 27, 29, 31-36,39,44, 46-63, 65, 66-76, 81-83, 85-95,97, 99-106, 108-115, 117-134, 137-144 and 149-154. It is more preferred that the diaromatic substituted compounds (III) be selected from the group of compounds of EXAMPLES 11, 17, 23, 25, 32, 44, 46, 47, 53, 68, 73, 81, 83, 85, 86, 90, 95, 99, 105, 106 and 132. XI3 is a good leaving group. When R, is -(CHj),- it is preferred that X,3 is -Cl, and when R, is -CO- it is preferred that XI3 is -Cl or -OH where the hydroxy portion is activated by an aģent such as l,r-carbonyldiimidazole.

The substituted linkers (II) are either known to those skilled in the art (in particular see International Publication No. WO 87/01797, PREPARATION A-l thru PREPARATION A-50) or can readily be prepared be prepared from known compounds by methods well known to those skilled in the art.

The coupling of aromatic-connectors (I) with the substituted linkers (II) to forrn the diaromatic substituted compounds (III) is a very well known reaction. When Z is the molecular fragment (Z-III) which is piperazine, the substituted linker (II) is a secondary -25- LV 10264 amine and the reaction with the appropriate aromatic-connector (I) producēs diaromatic substituted compounds (III) which depending on the nature of R, is a tertiary amine or an amide. The reaction to producē tertiary amines or amides from cyclic amines such as piperazine is very well known to those skilled in the art and requires no special mention. 5 See International Publication Nos. WO 87/01797 and WO 88/08424.

An altemative method of preparing the diaromatic substituted compounds (III) is to modify a compound which has the basie formula [aryl/heteroaryl]-connector-piperazine-[aryl/heteroarylJ. For example, nitro substituted compounds are not within the scope of the diaromatic substituted compounds (III). PREPARATIONS 22 and 129 10 and EXAMPLE 52 disclose the reduetion of a nitro compound (PREPARATIONS 10, 17 and 35) which has the aromatic-connector (I) portion already coupled with the substituted Iinker (II), but is not a diaromatic substituted compound (III) because the pyridine moiety is substituted with a nitro group which is outside the scope of the diaromatic substituted compounds (III). Reduetion of the nitro group and reduetive 15 amination producēs a monoalkyl or dialkylamino group of the diaromatic substituted compound (ΠΙ).

Another method of producing a diaromatic substituted compound (III) in which the eonneetor R, is -CH2- is by reduetion of the -CO- eonneetor of the corresponding diaromatic substituted compound (III), see CHART B and EXAMPLES 7 and 20. 20 The anti-AIDS piperazines (IV) are the compounds prepared by the procedures of EXAMPLES 1, 3-5, 7, 12, 16, 26, 28, 37, 38, 42,45, 64, 77, 78, 80, 84, 107,116, 135,136 and 145-148. Preferred are the compounds of EXAMPLES 16,26, 38,45 and 64. Most preferred is the compound of EXAMPLE 16. It is preferred that the compound of EXAMPLE 16 be in a salt forrir, the preferred salt is the mesylate. 25 The diaromatic substituted compounds (ΠΙ), the anti-AIDS piperazines (TV), the indoles (V) and the anti-AIDS amines (X) are amines and as such form acid addition salts when reacted with acids of sufficient strength to producē the corresponding salts. The salts are preferred over the free amines since they producē compounds which are more water soluble and more crystalline. Phārmaceutically acceptable salts inelude salts 30 of both inorganic and organic acids. The preferred pharmaceutically acceptable salts inelude salts of the following acids: methanesulfonic, hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, benzoic, citric, tartaric, fumaric, maleic, p-toluenesulfonic, benzenesulfonic, CHj-(CHj)a-COOH where n is 0 thru 4, HOOC-iCHJ.-COOH where -26- n is as defined above.

While ali four types of compounds (III), (IV), (V) and (X) are amines and therefore form acid addition salts, some of the variable substituents are acids and as such form base addition salts when reacted with bases of sufficient strength. The pharmaceu-tically acceptable salts include both inorganic and organic bases. The pharmaceutically salts are preferred over the free acids since they producē compounds which are more water soluble and more crystalline. The preferred pharmaceutically acceptable salts include salts of the follovving bases, for example, hydroxide, ammonia, tromethamine (ΤΉΑΜ), 2-amino-2-(hydroxymethyl)-l,3-propanediol. Suitable cations include, for example, sodium, potassium, calcium and magnesium.

The diaromatic substituted compounds (III), the anti-AIDS piperazines (IV) and the indoļes (V) are useful as inhibitors of virai reverse transcriptase, an enzyme neces-sary for human immunodeficiency virus replication and therefore would be useful in the treatment of of such diseases as AIDS.

The term human retrovirus (HRV) indicates human immunodeficiency virus type I, or strains thereof apparent to one skilled in the art, which belong to the same virai families and which create similar physiological effects in humāns as various human retro-viruses.

Patients to be treated would include those individuāls (1) infected with one or more than one strain of a human retrovirus as determined by the presence of either measurable virai antibody or antigen in theserum and (2) having either a $ymptomatic AIDS defining infection such as (a) disseminated histoplasmosis, (b) isopsoriasis, (c) bronchial and pulmonary candidiasis including pneumocystic pneumonia (d) non-Hodgkin’s Iymphoma or (e) Kaposi’s sarcoma and being less than sixty years old; or having an absolute CD4 lymphocyte count of less than 200/m3 in the peripheral blood.

The diaromatic substituted compounds (III), the anti-AIDS piperazines (IV) and the indoles (V) can be given orally. Suitable dosage forms include tablets, capsules, suspensions, Solutions and elixirs. An effective amount is from about 0,1 to about 500 mg/kg/day. A typical unit dose for a 70 kg human would be from about 10 mg to about 2000 mg, preferably about 100 mg to about 1000 mg taken one to six times per day.

The exact dosage and frequency of administration depends on the particular diaromatic substituted compounds (III), the anti-AIDS piperazines (IV) and the indoles (V) used, the particular condition being treated, the severity of the condition being -27- LV 10264 treated, the age, weight, general physical condition of the particular patient, other medication the individual may be taking as is well known to those skilled in the art and can be more accurately determined by measuring the blood Ievel or concentration of the diaromatic substituted compounds (III), the anti-AIDS piperazines (IV) and the indoles 5 (V) in the patient’s blood and/or the patient’s response to the particular condition being treated.

Patients who are HIV positive but asymptomatic would typically be treated with lower oral doses (about 0.2 to about 100 mg/kg/day. ARC (AIDS-related comp!ex) and AIDS patients would typically be treated with higher oral doses (about 1 to about 500 10 mg/kg/day).

The diaromatic substituted piperazines (III), the anti-AIDS piperazines (IV) and the indoles (V) of this invention can be be used in conjunction with other antiviral aģents such as AZT.

The utility of the diaromatic substituted piperazines (ΠΙ), the anti-AIDS 15 piperazines (IV) and the indoles (V) of this invention can be determined by their ability to inhibit virai reverse transcriptase, an enzyme essential for human immunodeficiency virus replication. This enzyme has characteristics which differentiate it from other known cellular polymerases and it is a unique enzyme which is not found in uninfected celis. Virai reverse transcriptase is found in extracts from bacterial clones prepared 20 according to the procedure described in AIDS Virus Reverse Transcriptase defined by high Ievel expression in Escherichia coli, EMBO J. 6:3133-3137 (1987). Inhibition of this enzyme is determined in a celi free assay which measures the ievel of radioactive precursors incorporated into DNA. Extracts prepared according to the procedure of Science, 1125-1129 (1981) are incubated in a mixture of inhibitor, 20 mM dithiothreitol, 25 60 mM sodium chloride, 0.05% NP-40, 10 mM magnesium chloride, 50 mM Tris pH 8.3, 10 /xM [35S]-labeled deoxynuleoside-5’-triphosphate, 10 /ig/ml RNA template (poly rC or poly rG) and 5 /xg/ml DNA primer (oligo dG or oligo dT) for 30 minūtes at 37°C. Incorporation of radio-labeled percursor is determined by spotting aliquots of the reaction mixture on DE81 paper, vvashing the papērs to remove unincorporated percursor, drying 30 and determining counts. The results flCw means the concentration, in μΜ of drug, required to inhibit the reverse transcriptase activity to the extent of 50%) of various assay(s) are combined and reported as % inhibition and IC» (calculated).

The utility of this invention is further demonstrated by the ability of the -28- diaromatic substituted compounds (III), the anti-AIDS piperazines (IV) and the indoles (V) to inhibit HlV-induced syncytia formation in a tissue culture assay using MT-2 celis infected with HIV-1. This tēst is described in Quantitative Infectivity Assay for HIV-1 and -2., Nature 332: 469-470, 1988 as well as in AIDS RESEARCH AND HUMAN 5 RETROVIRUSES, Vol. 4, No. 6, pages 449-455 (1988), Mary Ann Liebent, Inc., Publishers; in an article entitled "Nucleotide Dimers Suppress HIV Expression In VITRO". The results (ICJ0 means the concentration, in μΜ of drug, required to inhibit syncytia formation to the extent of 50%) of various assay(s) are combined and reported as % inhibition and IC50 (calculated). The known commercial compound, AZT, 10 exhibited anti-HIV potency in this assay with 100 percent and 50 percent reduction in syncytia formation at concentrations of approximately \μΜ and 0.5 μΜ, respectively.

DEFINITIONS AND CONVENTIONS

The definitions and explanations below are for the terms as used throughout this entire document including both the specification and the claims.

15 I. CONVENTIONS FOR FORMULAS AND DEFINITIONS OF VARIABLES

The Chemical formulas representing various compounds or molecular fragments in the specification and claims may contain variable substituents in addition to expressly defined structural features. These variable substituents are identified by a letter or a letter followed by a numerical subscript, for example, "Z," or "Rj" where "i" is an 20 integer. These variable substituents are either monovalent or bivalent, that is, they represent a group attached to the formula by one or two Chemical bonds. For example, a group Z, vvould represent a bivalent variable if attached to the formula CH3-C(=Z,)H. Groups Ķ and Rj vvould represent monovaļent variable substituents if attached to the formula CHj-CH2-C(Rļ)(Rj)H. When Chemical formulas are dravvn in a linear fashion, 25 such as those above, variable substituents contained in parentheses are bonded to the atom immediately to the left of the variable substituent enclosed in parenthesis. When two or more consecutive variable substituents are enclosed in parentheses, each of the consecutive variable substituents is bonded to the immediately preceding atom to the left which is not enclosed in parentheses. Thus, in the formula above, both Rj and Rj are 30 bonded to the preceding carbon atom.

Chemical formulas or portions thereof dravvn in a linear fashion represent atoms in a linear chain. The symbolin general represents a bond betvveen two atoms in the Chain. Thus CH3-0-CH2-CH(Rj)-CHj represents a 2-substituted-l-methoxypropane -29- LV 10264 compound. In a similar fashion, the symbol "=" represents a double bond, e.g., CH2=C(Ri)-0-CHj, and the symboI" = " represents a triplebond, e.g., HCeC-CHiRi)-CH2-CHj. Carbonyl groups are represented in either one of two ways: -CO- or -C(=0)-, with the former being preferred for simplicity. 5 Chemical formulas of cyclic (ring) compounds or molecular fragments can be represented in a linear fashion. Thus, the compound 4-chloro-2-methylpyridine can be represented in linear fashion by N*=C(CH3)-CH=CCI-CH=C'H with the convention that the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring. Likewise, the cyclic molecular fragment, 4-(ethyI)-l-piperazinyl can 10 be represented by A rigid cyclic (ring) structure for any compounds herein defines an orientation with respect to the planē of the ring for substituents attached to each carbon atom of the rigid cyclic compound. For saturated compounds which have two substituents attached to a carbon atom which is part of a cyclic system, -C(Xt)(X2)’ the two substituents may 15 be in either an axial or equatorial position relative to the ring and may change between axial/equatorial. Hov/ever, the position of the .two substituents relative to the ring and each other remains fixed. While either substituent at times may lie in the planē of the ring (equatoriaI) rather than above or below .the planē (axial), one substituent is always above the other. In Chemical structural formulas depicting such compounds, a substituent 20 (X,) which is "below" another substituent (Χ2) will be identified as being in the alpha (or) configuration and is identified by a broken, dashed or dotted line attachment to the carbon atom, i.e., by the $ymbol- ·" or"...". The corresponding substituent attached "above" (Xj) the other (Χ^ is identified as being in the beta 03) configuration and is indicated by an unbroken line attachment to the carbon atom. 25 When a variable substituent is bivalent, the valences may be taken together or separately or both in the defmition of the variable. For example, a variable Ķ attached to a carbon atom as -C(=RJ- might be bivalent and be defined as 0x0 or keto (thus forming a carbonyl group (-CO-) or as two separately attached monovalent variable substituents a-R*.,· and /3-R<.k. When a bivalent variable, Rj, is defined to consist of two 30 monovalent variable substituents, the convention used to define the bivalent variable is of the form or some variant thereof. In such a case both a-Rw and β-Κ.^ are attached to the carbon atom to give -C(a-Ri.j)03-Ri.k)-. For example, when the bivalent variable R*, -C(=R<)- is defined to consist of two monovalent variable substit- -30- uents, the two monovalent variable substituents are o-R^^Rm.....etc, giving ···· *C(a*R«.9) (j5-R«.,oh etc. Likewise, for the bivalent variable Rn, -C(=RU)-, two monovalent variable substituents are deR,,.,:^,,.^ For a ring substituent for which separate a and β orientations do not exist (e.g. due to the 5 presence of a carbon carbon double bond in the ring), and for a substituent bonded to a carbon atom which is not part of a ring the above convention is stili used, but the α and β designations are omitted.

Just as a bivalent variable may be defined as two separate monovalent variable substituents, two separate monovalent variable substituents may be defined to be taken 10 together to form a bivalent variable. For example, in the formula -Ο,Ο^Η-ί^Ο^Η- (C, and Cļ define arbitrarily a first and second carbon atom, respectively) R* and Rj may be defined to be taken together to form (1) a. second bond between Q and C2 or (2) a bivalent group such as oxa (-0-) and the formula thereby describes an epoxide. When R, and Rj are taken.together to form a more complex entity, such as the group -Χ-Υ-, 15 then the orientation of the entity is such that C! in the above formula is bonded to X and Cj is bonded to Y. Thus, by convention the designation "... R< and Rj are taken together to form -CHj-CHj-O-CO- ..." means a lactone in which the carbonyI is bonded to C2. However, when designated "... Rj and R, are taken together to form -C0-0-CH2-CH2-the . convention means a lactone in which the carbonyl is bonded to C,. 20 The carbon atom content of variable substituents is indicated in one of two ways.

The first method uses a prefix to the entire name of the variable such as "C,-C4", where both T and "4" are integers representing the minimum and maximum number of carbon atoms in the variable. The prefix is separated from the variable by a space. For example, "Cj-C4 alkyl" represents alkyl of l.through 4 carbon atoms, (including isomeric 25 forms thereof unless an express indication to the contrary is ģiven). Whenever this single prefix is given, the prefix indicates the entire carbon atom content of the variable being defined. Thus Cj-C* alkoxycarbonyl describes a group CHj-fCH^-O-CO- where 0 n is zero, one or two. By the second method the carbon atom content of only each portion of the definition is indicated separately by enclosing the "Cj-C/ designation in 30 parentheses and placing it immediately (no intervening space) before the portion of the definition being defined. By this optional convention (C,-C})alkoxycarbonyl has the same meaning as Q-C4 alkoxycarbonyl because the "C,-C," refers only to the carbon atom content of the alkoxy group. Similarly while both Cj-C4 alkoxyalkyl and (C,- -31- LV 10264 C3)alkoxy(C1-CJ)a!kyl define alkoxyalkyI groups containing from 2 to 6 carbon atoms, the two definitions differ since the former defmition allows either the alkoxy or alkyl portion alone to contain 4 or 5 carbon atoms while the latter defmition limits either of these groups to 3 carbon atoms.

When the claims contain a fair!y complex (cyclic) substituent, at the end of the phrase naming/designating that particular substituent will be a notation in (parentheses) which will correspond to the same name/designation in one of the CHARTS which will also set forth the Chemical structural formula of that particular substituent.

Π. DEFINITIONS

Ali temperatures are in degrees Centigrade. TLC refers to thin-layer chromatography. THF refers to letrahydrofuran.

Saline refers to an aqueous saturated sodium chloride solution. N"MR refers to nuclear (proton) magnetic resonance spectroscopy, Chemical shifts are reported in ppm (δ) downfieId from tetramethylsilane. IR refers to infrared spectroscopy. CMR refers to C-13 magnetic resonance spectroscopy, Chemical shifts are reported in ppm (δ) downfield from TMS, EDC refers to l-ethyl-3*(3-dimethylaminopropyl)carbiodimide, •Φ refers to phenyl (C6Hj). MS refers to mass spcctrometry expressed as m/e or mass/eharge unit. [M + H]+ refers to the positive ion of a parent plus a hydrogen atom. EI refers to electron impact. CI refers to Chemical ionization. FAB refers to fast atom bombardment.

Ether refers to diethyl ether.

Pharmaceutically acceptable refers to those properties and/or substances which are acceptable to the patient from a pharmacological/toxicological point of view and to the manufaeturing pharmaceutical chemist from a physical/chemical point of view regarding composition, formulation, stability, patient acceptance and bioavailability.

Pyridinyl refers to the pyridyl radical as defined by IUPAC nomenclature. For example, 2-pyridyl (pyridine ring substituted in the 2-position).

The compounds of this invention are.· named (when possible) by the following method: first the [aryl/heteroaryl] moiety, next the aryl/heteroaryl portion of the I. substituted linker (II) and last the linker (Z) itself, however a few were named by other -32-

It methods for simplicty and convenience. The names of the radicals within each group follow the IUPAC convention.

When solvent pairs are used, the ratios of solvents used are volume/volume (v/v). 5 HIV refers to HIV-1.

Treatment refers to inhibition of the HIV virus and will differ depending on the infected individual. For individuāls who are HIV positive (infected) but who are asymptomatic, the diaromatic substituted compounds (III), the anti-AIDS piperazines (IV) and the indoles (V) will de!ay, or prevent, the onset of symptoms. For individuāls who 10 are HIV positive, symptomatic and are pre-AIDS or ARC patients, the diaromatic -substituted compounds (III), the anti-AIDS piperazines (IV) and the indoles (V) will delay, or prevent, the onset of "full blown AIDS". For individuāls who have "full blown AIDS", the diaromatic substituted compounds (ΠΙ), the anti-AIDS piperazines (IV) and the indoles (V) will extend survival time of these individuāls.

15 EXAMPLES

Without further elaboration, it is believed thatone sfcilled in the art can, using the preceding description, practice the present invention to its fullest extent. The following detailed examples describe how to prepare the various compounds and/or perform the various processes of the invention and are to be construed as merely illustrative, and not 20 limitations of the preceding disclosure in any way whatsoever. Those skilled in the art vvill promptly recognize appropriate variations from the procedures both as to reactants and as to reaction conditions and techniques. PRJEPARATION 1 4-Bromo-2,6-dimethylanisole

Bromine (31.15 g) is added dropvvise to an ice-cold solution of 2,6-dimethyl-25 anisole (18.96 g) in chloroform (300 ml). After the addition is complete, the reaction is allowed to stir at ambient temperature ovemight. The chloroform solution is vvashed with cold water (2 x), once with an aqueous saturated solution of sodium bicarbonate, and then again with vvater. The chloroform extract is dried over sodium sulfate and concentrated under reduced pressure a Iiquid, which is distilled to give the title 30 compound, bp. 557.1.5 mm mercury. PREPARATION 2 3,5-Dimethyl-4-methoxybenzoic acid ethyl ester A solution of 4-bromo-2,6-dimethylanisoIe (PREPARATION 1, 12.98 g) in tetrahydrofuran (40 ml) is added drop by drop to a mixture of magnesium tumings (1.87 -33- LV 10264 g) in tetrahydrofuran (5 ml). The Grignard reaction is initiated with iodine crystals. After the addition is complete, the mixture is refluxed for 2 hours. The Grignard reaģent is cooled to about 10° and then a solution of ethyl chioroformate (7.5 ml) in tetrahydrofuran (40 ml) is added in a 2 minūte period. The mixture is stirred for 45 5 minūtes at ice-water temperature and thenat 20-25° for 2 hours. The reaction is quenched with a saturated solution of ammonium chloride and diluted with ether. The phases are separated, the organic phase is washed vvith water and then with saline, dried over sodium sulfate, and concentrated under reduced pressure to give the title compound. PREPARATION 3 3,5-Dimethyl-4-methoxybenzoic acid (I)

10 A mixture of 3,5-dimethyl-4-methoxybenzoic acid ethyl ester (PREPARATION 2, 10.5 g) and aqueous sodium hydroxide (20%, 100 ml) is refluxed for 18 hours. The solution is cooled and acidified vvith hydrochloric acid (12N, pH 2). The acidified solution is extracted vvith chloroform (3 X). The combined extracts are dried over sodium sulfate and concentrated under reduced pressure to give a solid vvhich is 15 recrystallized from ether/pet ether mixture to give the title compound, mp 189-191°. PREPARATION 4 3,5-Dimethyl-4-methoxybenzyl chloride (I)

Hydrogen chloride gas is bubbled into a solution of formaldehyde (37%), glacial acetic acid (100 ml), and 2,6-dimethylanisole (21.8 g). After a short period of time, an exothermic reaction occurs and the reaction temperature risēs to about 40°. The reaction 20 mixture is cooled to about 20° vvith an ice bath. Hydrogen chloride gas is continualIy bubbled through the reaction solution for 5.5 hours. A gas chromatogram indicates the starting material is consumed. The hydrogen chloride bubbling is discontinued and the solution is then heated on a steam bath for 15 minūtes. After cooling to 20-25°, the reaction is diluted vvith vvater and ether. The phases are separated and the aqueous phase 25 is extracted a second time vvith ether. The combined ether extracts are vvashed vvith vvater (3 x) and then vvith saline, dried over sodium sulfate, and concentrated under reduced pressure to a Iiquid, vvhich is distillation under a house vacuum to give the title compound, bp. 145-150°. PREPARATION 5 3,5-Dimethyl-4-hydroxybenzyl chloride (I) 30 3,5-DimethyI-4-methoxybenzyl chloride (I, PREPARATION 4, 1.8 g) is added to a solution of boron tribromide (1.5 m) in dichloromethane (70 ml) at 78°. The solution is allovved gradually to vvarm to 20-25° ovemight. The reaction is poured into an aqueous sodium bicarbonate solution, and the phases are separated. The dichloromet- -34- hane phase is washed once vvith water and then vvith concentrated hydrochloric acid. The dried (sodium sulfate) organic phase is concentrated under reduced pressure to give the title compound. PREPARATION 6 1-[1,l-Dimethylethoxycarbonyl]-4-[3-(propylamino)-2- 5 pyridinyl]piperazine t·

Sodium cyanoborohydride (0.31 g) is added to a cold solution of 1-[1,1-dimethylethoxycarbonyl]-4-(3-amino-2-pyridinyI]piperazine (International Publication No. WO 88/08424, 2.8 g), propional (.87 g), and methanol (15 ml). After the exotherm has subsided, the reaction is stirred at 20-25° ovemight. The reaction is acidified (pH 10 2) with aqueous hydrochloride and then diluted with dichloromethane. The pH is adjusted with aqueous ammonium hydroxide (pH 8), and the phases are separated. The organic phase is dried over sodium sulfate, and concentrated under reduced pressure to a crude product which is dissolved in diethyl ether and allovved to crystallize at -5°. The solid is identified as starting material. The mother liquor is concentrated in vacuo to 15 give the title compound. PREPARATION 7 l-[3-(Propy!amino)-2-pyridinyl]piperazine (Π)

Trifluoroacetic acid (4 ml) is added to a solution of crude l-[l,l-dimethylethoxy-carbonyl]-4-[3-propylamino)-2-pyridinyl]piperazine (PREPARATION 6, 1.2 g) in dichloromethane (15 ml) chilled to -78°. The coolant is removed and the reaction is 20 allovved to warm to 20-25° for 3 hours. The solvents are removed in vacuo and the residue is redissolved in dichloromethane and aqueous saturated potassium carbonate. The phases are separated. The organic phase is washed with water, dried over sodium sulfate, and concentrated to the title compound. PREPARATION 8 l-[l,l-Dimethylethoxycarbonyl]-4-[3-(l-methylethylamino)- 25 2-pyridinyl]piperazine l-[l,l-Dimethylethoxycarbonylj-4-[3-amino-2-pyridinyl]piperazine(Intemational Publication 88/08424, 2.0 g) is dissolved in 35 ml of methanol and acetone (0.48 g) is added. The reaction is cooled to 0° and acetic acid (to pH 4.0) is added. The reaction is stirred 15 min at 0° and then sodium cyanoborohydride (0.50 g) is added. The 30 reaction is allowed to warm slowly to 20-25° and followed by TLC until completion. Additional acetic acid, sodium cyanoborohydride and acetone are sometimes necessary to force the reaction to completion. The reaction is diluted with chloroform (100 ml), washed vvith saturated aqueous sodium bicarbonate (50 ml), saline (75 ml), dried over -35- LV 10264 anhydrous sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (75 g silica gel, 4:l hexane/ethyl acetate) affords the title compound, NMR (300 MHz, CDCIj) 7.67, 6.91. 4.15, 3.57, 3.00, 1.48 and 1.23 δ. PREPARATION 9 l-[3-(l-Methylethylamino)-2-pyridinyl]piperazine (II) l-[l,l-Dimethylethoxycarbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (PREPARATION 8) is dissolved in methylene chloride (56 ml) and cooled to 0°. Then trifluoroacetic acid is added dropwise. The reaction is warmed to 20-25° and additional trifluoroacetic acid is added (26.6 g). When the reaction is complete by TLC, it is poured into 200 ml of water and ice, basified to.pH 12 with 2N aqueous sodium hydroxide, and extracted with 10 % tetrahydrofuran/chloroform (2 1) follovved by 10 % methanol/chloroform (1 1). The organic layers are dried over anhydrous sodium sulfate, concentrated in vacuo, and used without further purification, NMR (300 MHz, CDC13) 7.65, 6.85, 6.76, 4.16, 3.50, 2.98 and 1.20 δ. PREPARATION 10. l-[Indolyl-2-carbonyl]-4-(3-nitro-2-pyridinyl)piperazine l-(3-Nitro-2-pyridinyl)piperazine (2.58 g) is dissolved in methylene chloride (25 ml). Pyridine (1.031 g) is added and the reaction is cooled to 0°. Indole-2-carbonyl chloride (2.23 g) in methylene chloride (6 ml) is added dropwi$e. The reaction is stirred for 30 minūtes at 0°, diluted v/ith methylene chloride (50 ml), washed with saturated aqueous sodium bicarbonate (60 ml), saline (70 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude residue is recrystallized from methanol/toluene (200 ml, 10/90) to give the title compound, mp 205-207°. PREPARATION 11 l-(2-Nitrophenyl)piperazine

Piperazine (24.46 g) is dissolved in acetonitrile (200 ml) and anhydrous potassium carbonate (10.47 g) is added. Then 2-chloronitrobenzene (10.0 g) is added dropwise, After stirring 1 hr at 20°, the reaction mixture is diluted with methylene chloride, washed with water, and saturated aqueous potassium carbonate. After drying over anhydrous sodium sulfate, the reaction mixture is concentrated under reduced pressure to give the title compound, NMR (300 MHz,· CDClj) 7.75, 7.49, 7.14, 7.04, 3.03 and 1.93 3. PREPARATION 12 l-[l,l-Dimethylethoxycarbonyl]-4-(2-nitrophenyl)piperazine

Di-t-butyldicarbonate (5.24 gj is added to a 0° solution of l-(2-nitrophenyl)-piperazine (PREPARATION 11,5.0 g) and triethylamine (3.7 ml) in methylene chloride (48 ml). The reaction is warmed to 20-25° after 20 min and stired 3.5 hr. Then the -36- reaction is diluted with methylene chloride, vvashed with saturated aqueous sodium bicarbonate, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the titie compound. PREPARATION 13 l-[l,l-Dimethylethoxycarbonyl]-4-(2-aminophenyI)- piperazine l-[l,l-Dimeihyleihoxycarbonyl]-4-(2-nitrophenyl)piperazine (PREPARATION 12, 7.61 g) is dissolved in ethanol (150 ml). Palladium on carbon (10%, 0.75 g) is added and the reaction is hydrogenated at 45 psi for 6 hr. The mixture is filtered thm celite and concentrated under reduced pressure to give the titie compound. PREPARATION 14 1-[1, l-Dimethylethoxycarbonyl]-4-[2-(ethylamino)phenyl] piperazine

Sodium cyanoborohydride (1.6 g) is added to a 0° solution of l-[l,l-dimethyl-ethoxycarbonyl]-4-(2-aminophenyl)piperazine (PREPARATION 13, 6.52 g) and acetaldehyde (1.48 ml) dissolved in methanol (65 ml). After 3 hr the reaction mixture is partially concentrated under reduced pressure. Then it is diluted with chloroform, washed with saturated aqueous sodium bicarbonate, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the titie compound, R< = 0.62 (ethyl acetate/hexane, 1/1), NMR (300MHz, GDC1,) 7.04, 6.95, 6.66, 4.59, 3.70-3.50, 3.15, 2.82, 1.49 and 1.28 a. PREPARATION 15 l-[2-(Ethylamino)phenyl]piperazine (II) ·

Follov/ing the general procedure of PREPARAΉON 7 and making non-critical variations but using l-[l,l-dimethylethoxycarbonyl]-4-(2-ethylaminophenyl)piperazine (PREPARATION 14, 8.61 g), the titie compounds is obtained, Rf = 0.2 (methanol/triethylami ne/chloroform , 1 /1 /98). PREPARATION 16 5-Fluoroindole-2-carbonyl chloride (I) 5-Fluorindole-2-carboxyIic acid is dissolved in oxalylchloride and stirred 24 hr at 20-25° in the dark. The reaction mixture is concentrated under reduced pressure to give the titie compound. PREPARATION 17 l-[5-FIuoroindolyl-2-carbonyl]-4-[(3*nitro)-2-pyridinyl]- piperazine

Follovving the general procedure of PREPARATION 10 and making non-critical variations but starting with 5-fluoroindole-2-carbonyl chloride (PREPARATION 16), the titie compound is obtained, NMR (300 MHz, CDC13) 9.41, 7.80, 7.35,7.27, 7.05,7.01, -37- LV 10264 6.88, 6.77, 4.08, 3.83 and 3.24 δ. PREPARATION 19 Ethyl 5-methoxy-4,5,7-trimethylindole-2-carboxylate A solution of sodium nitrite (1.91 g) in water (4.4 ml) is added (below the surface) to a cold (-10°) thick slurry of 2)3,5-trimethyl-4-methoxyaniline [J. Amer. Chem. Soc., 70 2656 (1948)] in ethanol (10 ml), vvater (54 ml) and concentrated hydrochloric acid (9.3 ml). The mixture is stirred for 30 min as the temperature risēs to -1°, then the solution of the diazonium salt is poured into a vigorously stirred mixture of ethyl methylacetoacetate (3.68 g) in ethanol (24 ml) containing potassium hydroxide (45%, 6 ml) and ice (40 g). The mixture is allowed to warm to 20-25Q with continued stirring for 1 hr, then is extracted with toluene. The toluene extracts are dried (potassium carbonate) and concentrated to give an oil. A solution of the oil in ethanol (20 ml) is stirred vvhile hydrogen chloride rapidly with an exotherm to 60°. The mixture is cooled and saturated with hydrogen chloride at 45°, then is stored ovemight at 5°. The precipitate is collected and washed several times with cold ethanol. The solid is partitioned betveen ethyl acetate and aqueous bicarbonate, the phases separated, the organic phases dried and concentrated. The concentrate is crystallized from ace-tone/hexane to give the title compound, mp 182-183°. PREPARATION 20 5-Methoxy-4,6;7-trimethylindole-2-carboxylic acid (I) A solution of ethyl 5-methoxy-4,5,7 trimethylindole-2-carboxylate (PREPARA-TION 19, 1.04 g) in ethanol (30 ml) containing potassium hydroxide (45%, 2.5 ml) is heated under reflux for 1,5 hr. The mixture is acidified with acetic acid (2 ml) and concentrated under reduced pressure. The residue is mixed with water (200 ml) and filtered. The filter cake is washed with water and dried to give the title compound. PREPARATION 21 1 -(3-( 1,1 -Dimethylethylamino)-2-pyridinyl]piperazine

Isobutylene (10 ml) is condensed into a solution of l-[l,l-dimethylethoxy-carbonyl]-4-[3-amino-2-pyridinyl]piperazine (International Publication No. WO 88/08424, 200 mg) in methylene chloride (10 ml) at -70°. Phosphoric acid (85%, 50 μ\) is added and the mixture stirred for 60 minūtes. Boron trifluoride etherate (200 μΐ) is added dropwise and the resulting suspension is stirred 8 hours at reflux and ovemight at 20-25° allowing the isobutylene to evaporate. The suspension is diluted with water and ammonium hydroxide is added until basie to pH paper and then extracted with methylene chloride (3 x). The combined extracts are dried over anhydrous potassium carbonate, filtered, and concentrated under reduced pressure to a liquid which is flash -38- chromatographed (silica gel, 230-400 mesh), eluting with methanol/chloroform (3/20). The appropriate fractions are pooled and concentrated to give an oil. The NMR, CMR, IR, and MS (m/e) M+ 234 support the title compound. PREPARATION 22 l-[Indolyl-2-carbonyl]-4-[3-amino-2-pyridinyl]piperazine l-pndolyl-2-carbony]]-4-(3-nitro-2-pyridinyl)piperazine (PREPARATION 10, 3.67 g) is suspended in dioxane (80 ml) and aqueous titanium trichloride (20%, 48.3 ml) is added in one portion. The reaction is stirred for 30 minūtes at 20-259, diluted with aqueous sodium hydroxide (2N, 100 ml), extracted with methylene chloride (3 x 100 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography (100 g silica gel) eluting with methanol/chloroform (3/97), pooling the appropriate fractions and concentrating them gives the title compound, mp 191-192°. PREPARATION 23 l-[l,l-Dimethylethoxycarbonyl]-4-(4-chloro-5-nitro-6- pyrimidyl]piperazine A solution of l-[l,l-dimethylethoxycarbonyl]piperazine (1.88 g) in dichloro-methane (30 ml) is added drop by drop over 1.5 hr to a solution of 4,6-dichloro-5-nitro-pyrimidine (1.94 g) and triethylamine (1.32 g) in dichloromethane (170 ml) at78°. After stirring an additional hr at -78°, the reaction js diluted with aqueous sodium bicarbonate (10%). The phases are separated, the organic phase is concentrated to a liquid which solidified on standing at 20-25°. The solid is dissolved in chloroform and flash chromatographed on silica gel eluting with methanol/chloroform (1/99), pooling and concentrating the appropriate fractions gives the title compound, Anal. Calc for CijHuN1C104; MW = 343.77: C.45.42; H.5.28; N,20.37; 0,10.31. Found: C.45.52; H.5.40; N,20.34; 0,10.36. PREPARATION 24 2-Chloro-3-(l-methylethylamino)pyrazine A solution of 2,3-dichloropyrazine (2.0 g) and isopropylamine (2.3 g) in toluene (8 ml) is refluxed for 40 hr. The mixture is cooled and filtered to remove isopropyl-amine hydrochloride. The filtrate is concentrated in vacuo to a residue which is diluted with an aqueous sodium hydroxide solution (10%) and dichloromethane. The phases are separated. The dichloromethane phase is vvashed vvith saline, dried over sodium sulfate, and concentrated to give the title compound, NMR (CD03) 1.28, 4.21, 5.02, 7.54 and 7.94 δ. PREPARATION 25 1-(2-(1-Methylethylamino)-3-pyrazinyl]piperazine (II) -39- LV 10264 A solution of2-chloro-3-(l-methylethylamino)pyrazine (PREPARATION 24,1.6 g) and piperazine (4.3 g) in xvlene (10 ml) is refluxed for 26 hr. The mixture is cooled to 0o and diluted with concentrated hydrochloric acid (8 ml). The xylene is decanted and ether is added and also decanted from the salts. The salts are diluted with excess aqueous sodium hydroxide (5%) and dichloromethane. The phases are separated. The aqueous phase is extracted three more times with dichloromethane. The combined organic extracts are dried over sodium sulfate and concentrated to give a liquid mixture which is flash chromatographed on silica gel eluting with methanol/chloroform (5/95). The appropriate fractions are pooled and concentrated to give the title compound, NMR (CDClj) 1.27, 1.83, 3.04 , 4.12 , 4.78 , 7.49 and 7.72 δ. PREPARATION 26 2-Chloro-3-(l,l-dimethylethylamino)pyrazine

Follovving the general procedure of PREPARATION 23 and making non-critical variations but starting with 2,3-dichloropyrazine (2.0 g), the title compound is obtained, NMR (CDClj) 1.48, 5.24, 7.51 and 7.91 δ. PREPARATION 27 l-[3-(l,l-DimethyIelhylamino)-2-pyrazinyl]piperazine(II)

Following the general procedure of PREPARATION 25 and making non-critical variations but starting with 2-chloro-3-(l,l-.dimethylethylamino)pyrazine (PREPARATION 26, 0.95 g) and piperazine, the title compound is obtained, NMR (CDC13) 1.47, 1.70, 2.99, 5.02, 7.46 and 7.69 δ. PREPARATION 28 l-[l,l-Dimethylethoxycarbonyl]-4-[5-amino-6-pyrimidinyl] piperazine A mixture of l-(l,l-dimethylethoxycarbonyl]-4-[4-chloro-5-nitro-6-pyrimidyl]*

I piperazine (PREPARATION 23, 0.56 g) and triethylamine (.3 ml) and palladium on car-bon (5%, .13 g) in ethanol (100 ml) is charged vvith hydrogen gas (30 psi). After the theoretical amount of hydrogen gas is consumed, the catalyst is removed under reduced pressure. The filtrate is concentrated under reduced pressure to a foam which is diluted with an aqueous saturated solution of potassium carbonate and dichloromethane. The phases are separated and the organic phase is dried over sodium sulfate and concentrated to give to give the title compound, NMR (CDClj) 1.49, 3.49, 3.29, 3.56,7.98, and 8.39 δ. PREPARATION 29 1 -[ 1,1 -Dimethylethoxycarbonyl]-4-[5-(l-methylethylamino)- 6-pyri midinyl]piperazine A solution of sodium cyanoborohydride (.13 g) in methanol (4 ml) is added to a -40- mixture of 1-(1, l-dimethylethoxycarbonyl]-4-[5-amino-6-pyrimidinyl]piperazine (PREPARATION 28,0.44 g), acetone (3 ml), and glacial acetic acid (.4 ml) in methanol (7 ml) at 0°. The mixture is stirred at 20-25° for 72h. The reaction is diluted with an aqueous sodium hydroxide solution (10%) and dichloromethane, The phases are 5 separated and the organic phase is washed with water and the concentrated to a colorless liquid which is flash chromatographed on silica gel eluting with methanol/chloroform (1/99). The appropriate fractions are pooled and concentrated to give the title com-pound, NMR (CDClj) 1.26, 1.49, 3.2, 3.44, 3.5-3.62, 7.89 and’8^3 δ. PREPARATION 30 l-[5-(l-Methylethylamino)-4-pyrimidinyl]piperazine(II) 10 Trifluoroacetic acid (5 ml) is added to a solution of I-(l,l-dimethylethoxy- carbonyl]-4-[5-(l-methylethylamino)-4-pyrimidinyl]piperazine (PREPARAΉON 29, 0.37 g) in dichloromethane (20 ml) at 78°. The reaction is allowed to warm to 20-25° ovemight, and then diluted with excess aqueous sodium hydroxide solution (10%). The phases are separated. The aqueous phase is extracted twice again with dichloromethane. 15 The combined organic extracts are washed with saline, dried over sodium sulfate, and concentrated under reduced pressure to give the title compound, NMR (CDClj) 1.25, 1.7, 3.01, 3.21, 3.45, 3.5, 7.86 and 8.34 δ. PREPARATION 31 3,5-Dichloro-4-(l-methylethylamino)pyridazine A solution of 3,4,5-trichloropyridazine (9.2 g) and isopropylamine (16.5 g) in 20 toluene (25 ml) is refluxed for 18 hr. Excess isopropylamine is removed by atmospheric distillation. The residual solution is cooled and diluted with dichloromethane and aqueous sodium hydroxide solution (5%). The phases are separated. The organic phase is washed with water and then with saline. The organic phase is dried over sodium sulfate and concentrated under reduced pressure to give a liquid which containes a 25 mixture of isomeric products. The isomers are separated by flash chromatography on silica gel eluting with ether/hexane (30/70). The appropriate fractions are pooled and concentrated to give the desired isomer, NMR (CDClj) 1.33, 4.59, 4.87 and 8.60 δ; CMR (CDClj) 24.2, 46.4, 117.1, 139.3, 145.5 and 151.3 δ.

Further elution gives 3,4-dichloro-5-(l-methylethylamino)pyridazine vvhich is 30 recrystallized from ether hexane, NMR (CDC13) 1.35, 3.87, 4.80, and 8.55 δ; CMR (CDClj) 22.6, 44.7, 116.5, 136.3, 142,5 and 153.4 δ. PREPARATION 32 l-[5-Chloro-4-(l-methylethyl)amino-3-pyridazinyl]* piperazine LV 10264 -4 ΙΑ mixture of 3,5-dichloro-4-(l-methylethyl)aminopyridazine (PREPARATION 31, 1.77 g) and piperazine (2.96 g) in xylene (18 ml) is refluxed for 40 hr. The mixture is cooled and then treated vvith concentrated hydrochloric acid (8 ml). After further cooling, a precipilate forms and the organic liquid is separated. The aqueous phase is diluted with an excess of a solution of aqueous sodium hydroxide (10%) and then is extracted with chloroform (3 x). The combined organic extracts are washed with water, then saline, dried over sodium sulfate, and concentrated to an oil. The crude product is flash chromatographed on silica gel eluting with methanol. The appropriate fractions are pooled and concentrated to give the title compound, NMR (CDClj) 1.20, 3.04, 3.18, 4,46, 4.73 and 8.50 δ; CMR (CDClj) 24.0, 44.3, 45.9, 50.2, 118.2, 135.8, 148.3 and 155.4 δ. PREPARATION 33 l-[4-(l-Methylethyl)amino-3-pyridazinyI]piperazine (II)

Follovving the general procedure of PREPARATION 28 and making non-critical variations but starting vvith l-[5-chloro-4-(l-methylethyl)amino-3-pyridazinyl]piperazine (PREPARATION 32, 1.7 g) and triethylamine (.81 g), the title compound is obtained, NMR (CDClj) 1.28, 2.06, 3.05, 3.11, 3.59, 4.75, 6.39, and 8.49 δ; CMR (CDClj) 22.2, 43.2, 46.2, 50.6, 103.7, 138.7, 148.4 and 154.5 δ. PREPARATION 34 N.^-Dimetf^l-N-p-nitro^^rid^Oetl^lenediamine

To a solution of N,N’-dimethylethylenediamine (3.2 ml) and potassium carbonate (830 mg) in acetonitrile (15 ml) stirred at 20-25° under a nitrogen atmosphere is added a solution of 2-chloro-3-nitropyridine (500 mg) in acetonitrile (10 ml) over one hour. «·

The mixture is concentrated under reduced pressure and partitioned betvveen methylene chloride (75 ml) and vvater (25 ml). The phases are separated and the aqueous phase is extracted vvith methylene chloride (25 ml) and the total organics are dried vvith saline and sodium sulfate. Concentration under reduced pressure gives the title compound, NMR (CDClj) 8.29, 8.10, 6.69, 3.85, 2.90, 2.88 and 2.46 δ. PREPARATION 35 N,N,-Dimethyl-N-(indolyl-2-carbonyl)-N,-(3-nitro-2- pyridinyl)ethylenediamine l,r-carbonyldiimidazole (551 mg) is added to a solution of indole-2-carboxylic acid (516 mg) in dry tetrahydrofuran (8 ml). The mixture is stirred one hour at 20-25° andN,N’-dimethyl-N-(3-nitro-2-pyridinyl)ethylenediamine(PREPARATION34,674mg) is added as a solution in tetrahydrofuran (4 ml) via a canula, rinsing in vvith tetrahydro-furan (2 ml). The mixture is stirred l hr and concentrated to a gum, diluted vvith -42- methylene chloride (100 ml), vvashed with water and saline and dried over sodium sulfate. Removal of solvent under reduced pressure gives a solid which is recrystaJlized from methylene chloride/ethvl ether to give the title compound, mp 172.5 · 173°. PREPARATION 36 2-(N-Methyl-N-(3-nitro-2-pyridinyl)amino)ethanol 5 2-(Methylamino)ethanol (3.04 ml) is added to a mixture of 2-chloro-3-nitro- pyridine (3.00 g) and of potassium carbonate (5.22 g) in acetonitrile (90 ml) at 0°. Tfie mixture is stirred for 2.5 hr at 20-25° and additional 2-(methylamino)ethanol (1.5 ml) is added. The mixture is stirred for 1.5 hr, concentrated to a gum and diluted with methylene chloride (85 ml) and water (20 ml). The layers are separated and the organic 10 phase is vvashed vvith vvater and dried over magnesium sulfate. Removal of solvent under reduced pressure gives the title compound, NMR (CDC13) 8.27, 8.14, 6.76, 4.38, 3.88 and 2.87 6. PREPARATION 37 2-(N-Methyl-N-(3-nitro-2-pyrid-2-yl)amino)ethylindole-2- carboxylate 15 Indole-2-carboxylic acid (468 mg), 1,3-dicyclohexylcarbodiimide (595 mg), and 4-dimethylaminopyridine (71 mg) are added to 2-(N-methyl-N-(3-nitro-2-pyridinyl)-amino)ethanol (PREPARATION 36, 571 mg) in dry methylene chloride (20 ml). The mixture is stirred at 20-25° for 22 hr after which additional l,3-dicyclohexylcarbodiimide (180 mg), 4-dimethylaminopyridine (71 mg) and methylene chloride (10 ml) are added. 20 The mixture is stirred 4 hr, filtered and concentrated to dryness. The residue is taken up in ethyl acetate, filtered, vvashed vvith aqueous hydrochloric acid (10%), vvater, saline and dried over sodium sulfate. Removal of solvent under reduced pressure gives a solid vvhich is chromatographed on 70-230 mesh silica gel (90 g) eluting vvith a gradient of 10 - 50% ethyl acetate in hexane. The appropiiate fractions [TLC on silica gel, R* = 0.63, 25 ethyl acetate/hexane (50/50)] are pooled and removal of solvent gives the title compound, mp 124.1 - 125.1°. PREPARATION 38 N-Methyl-N-(2-hydroxyethyl)indole-2-carboxamide l,r-carbonyldiimidazole (1.11 g)'is added to a solution of indole-2-carboxyIic acid (1.0 g) in tetrahydrofuran (15 ml). The mixture is stirred 1 hour at 20-25° and 2-30 (methylamino)ethanol (5.0 ml) is added. The mixture is stirred 21 hours at 20-25° and 24 hours at reflux. The mixture is concentrated under reduced pressure, diluted vvith methylene chloride and extracted vvith vvater and saturated sodium bicarbonate. The phases are separated and the organic phase is dried vvith saline and sodium sulfate and -43- LV 10264 concentrated to give the crude product. Chromatography on silica gel with a metha* nol/chloroform gradient follovved by recrystallization from chloroform/ether to give the title compound, mp 141-142.5°. PREPARATION 39 2-(2-N-Methyl-N-(indolyl-2-carbonyl)amino)ethoxy)-3- aminopyridine

Sodium hydride in oil (60%, 48 mg) is added to a solution of N-methyl-N-(2-hydroxyethyl)indole-2-carboxamide (PREPARATION 38,250 mg)indimethylformamide (10 ml). The mixture is stirred 10 minūtes and 2-chloro-3-nitropyridine (164 mg) is added. The mixture is stirred 20 minūtes at 20-25°, diluted with water (20 ml) and concentrated under reduced pressure. The residue is dissolved in methylene chloride and extracted with water. The phases are separated and the organic layer is dried with saline and sodium sulfate. The solution in concentrated under reduced pressure and the residue is dissolved in methanol. Palladium black (200 mg) is added and the mixture is stirred 2 hours under an atrņosphere of hydrogen gas·: The mixture is filtered and concentrated. Chromatography on silica gel vvith a methanol/chloroform gradient gives the title compound, mp 156-158°. PREPARATION 40 2-(2-Hydroxyethoxy)-3-nitropyridine

Sodium hydride in oil (60%, 131 mg) is added to ethylene glycol (6.0 ml) and 2-chloro-3-nitropyridine (430 mg) is added. The mixture is stirred for 26 hours during which time additional sodium hydride in oil (60%, 100 mg) is added. Water is added, the pH is adjusted to 9 and the solution is extracted with methylene chloride (3 x 50 ml). The combined organic Iayers are dried with saline and sodium sulfate and concentrated. Chromatography on silica gel vvith a methanol/chloroform gradient affords the title compound, Rr = 0.32 (TLC on silica gel, ethyl acetate/hexane [50/50]). PREPARATION 41 2-(2-(Indolyl-2-carbonyl)ethoxy)-3-nitropyridine

Indole-2-carboxylic acid (109 mg), l,3-dicyclohexylcarbodiimide (140 mg), and dimethylaminopyridine (17 mg) are added to a solution of 2-(2-hydroxyethoxy)-3-nitropyridine (PREPARATION 40, 125 mg) in methylene chloride (7 ml). The mixture is stirred 18 hours at 20-25°, filtered and concentrated to dryness. The residue is taken up in ethyl acetate, filtered, vvashed vvith aqueous hydrochloric acid (10%), vvater, and saline dried over sodium sulfate and concentrated under reduced pressure. The residue is chromatographed on silica gel vvith ethyl acetate/hexane (15/85) to give the title compound, NMR (CDClj) 9.02, 8.35, 8.26,7.68, 7.41, 7.32, 7.25, 7.15, 7.04, 4,86 -44- and 4.75 δ. PREPARATION 42 3-Methylindole-2-carboxylic acid (I) 3-MethyIindoIe (0.50 g) is dissolvčd in THF (7 ml) and cooled to -78°. Then n-butyl lithium (1.6 M in hexane, 2.5 ml) is added dropvvise. Meanvvhile, dry carbon dioxide is bubbled through THF (14 ml) at -78° for 5 min. The mixture in the flask containing the indole is added via cannula and the reaction is allovved to slowly warm to 20-25°. The mixture is concentrated under reduced pressure to dryness and reconstituted with THF (7 ml) and cooled to -78°. Then t-butyl lithium (1.6 M pentane, 2.5 ml) is added dropvvise to the flask containing the indole and the mixture is stirred for 1 hr. Meanvvhile dry carbon dioxide is bubbled through THF (14 ml) at -78° and the above reaction is added via cannula to the cooled dry THF. After 1.5 hr at -78°, the reaction mixture is slowly warmed to 20-25°, ,then poured into hydrochloric acid (1 N) and extracted with methylene chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound, NMR (300 MHz, CDClj) 8.67, 7.57, 7.30-7.24, 7.05 and 2.56 δ. PREPARATION 43 l-(Indolyl-2-carbonyl]-4-[4-fluoro-2-nitrophenyl]piperazine l-(Indolyl-2-carbonyl)piperazine(1.0g) and 2r5-difluoronitrobenzene(0.68 g) are mixed together in 10 ml of acetonitrile and 0.72 g of potassium carbonate are added. The reaction is stirred 24 hr at 20-25° and then heated to 50° for 8 hr. The reaction is poured into water, and extracted with chloroform (3 x), dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography eluting with ethyl acetate/hexane (50/50) to THF/ethyl acetate (50/50) pooling and concentrating the appropriate fractions gives the title compound, NMR (300 MHz, CDClj) 7.65, 7.57, 7.46, 7.37-7.10, 6.82, 4.10 and 3.10 δ. PREPARATION 44 l-[Indolyl-2-carbonyl]-4-[2-amino-4-fluorophenyI]- piperazine l-[rndolyl-2-carbonyl]-4-[4-fluoro-2-nitrophenyl]piperazine (PREPARATION 43, 1.4 g) is dissolved in 90 ml of ethanol and 25 ml of THF. Then palladium on carbon (10%, 0.27 g) is added and the reaction is hydrogenated at 40 psi for 18 hr. The mixture is filtered through a plug of celite and concentrated under reduced pressure to give the title compound, NMR (300 MHz, CDClj) 7.65, 7.45, 7.27, 7.13, 6.88, 6,81, 6.48-6.37, 4.50-3.80 and 3.10-2.75 δ. PREPARATION 45 l-[Indolyl-2-carbonyl]-4-[5-fluoro-2-nitrophenyl]piperazine -45- LV 10264 l-(Indolyl-2-carbonyl)piperazine(0.70 g) and 2,4-difluoronitrobenzenc (0.33 ml) are mixed together in 7 ml of acetonitrile and 0.42 g of potassium carbonate are added. The reaction is stirred 24 hr at 20-25° and then heated to reflux for 12 hr. The reaction mixture is poured into water, and extracted with chloroform (3 X), dried over anhydrou$ 5 sodium sulfate and concentrated under reduced pressure to give the title compound, NMR (300 MHz, CDClj) 9.39, 7.96, 7.65, 7/43, 7.32-7.25, 7.14, 6.81-6.72, 4.13 and 3.18 5. PREPARATION 46 l-[Indolyl-2-carbonyl]-4-[2-amino-5-fluorophenyl]- piperazine 10 Following the general procedure of PREPARATION 44 and making non-critical variations but starting with l-[indolyl-2-carbonyl]-4-[5-fluoro-2-nitrophenyl]piperazine (PREPARATION 45, 0.84 g), the title compound is obtained. PREPARATION 47 l-[l,l-Dimethylethoxycarbonyl]-4-(3-(l-pynOlidinyl)-2- pyridinyl]piperazine 15 1-[1, l-Dimethylethoxycarbonyl]-4-[3-amino-2-pyridinyl]piperazine(International

Publication No. WO 88/08424, 0.50 g), 1,4-dibromobutane (0.21 ml) and potassium carbonate (0.30 g) are refluxed in 4 ml of acetonitrile for 1 week. After 1 week, additional dibromobutane (0.21 ml) is added and refluxing is continued for 3 days. The reaction mixture is poured into water, extrācted with methylene chloride, dried o.ver 20 anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate is purified by Flash column chromatography eluting with ethyl acetate/hexane (10/90) to ethyl acetate/hexane (25/75). The appropriate fractions are pooled and concentrated to give the title compound, NMR (300 MHz, CDClj) 7.78, 6.98, 6.78, 3.52, 3.20-3.10, 1.87 and 1.44 5. 25 PREPARATION 48 l-[3-(l-Pyrrolidinyl)-2-pyridinyl]piperazine (II) l-[l,l-Dimethylethoxycarbonyl]-4-[3-(l-pyrrolidinyl)-2-pyridinyl]piperazine (PREPARATION 47, 0.26 g) is dissolved in 1.3 ml of THF and cooled to 0°. Trifiuoroacetic acid (1.3 ml) is added and the reaction is stirred at 0° for 20 min, and then vvarmed to 20-25° for 20 min. Then the reaction is poured into 1 N aqueous sodium 30 hydroxide and extracted with methanol/chloroform (10/90, 2 X 50 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound, NMR (300 MHz, CDClj) 7.64 , 6.81, 6.61, 3.05-2.94, 2.86-2.79 and 1.78-1.65 5. -46- PREPARATION 49 l-(3-Nitro-2-pyridinyl)-l,4-diazepine

Homopiperazine (15.58 g) is dissolved in 100 ml of acetonitrile. Potassium carbonate (8.7 g) is added and then the 2-chloro-3-nitropyridine (5.0 g) dissolved in 25 ml of acetonitrile is added dropwise. The reaction is stirred at 20-25° 4 hr, then diluted with methylene chloride, washed vvith water (2 x), saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the tītie compound, NMR (300 MHz, CDClj) 8.30, 8.08, 6.66, 3.60, 3.41, 3.10, 2.89 and 1.93 δ. PREPARATION 50 l-(l,l-Dimethylethoxycarbonyl)-4-(3-nitro-2-pyridinyl)-l,4- diazepine

Following the general procedure of PREPARATION 12 and making non-critical variations but starting with l-(3-nitro-2-pyridinyl)-l,4-diazepine (PREPARATION 49, 7.06 g), the title compound is obtained, NMR (300 MHz, CDClj) 8.29, 8.05, 6.67, 3.76-3.29, 1.98, 1.34 and 1.29 δ. PREPARATION 51 1 -(1,1 -Dimethylethoxycarbonyl)-4-(3-amino-2-pyridinyl)- 1,4-diazepine

Follovving the general procedure of PREPARATION 13 and making non-critical variations but starting vvith l-(l,l-dimethylethoxycarbonyl)-4-(3-nitro-2-pyridinyl)-l,4-diazepine (PREPARATION 50, 6.0 g), title compound is obtained, NMR (300 MHz, CDClj) 7.75, 6.93, 6.81, 3.86, 3.78, 3.66-3.57,3.51, 3.36-3.2, 3.21,1.95, 1.85, 1.48 and 1.47 δ. PREPARATION 52 l-(l,l-Dimethylethoxycarbonyl)-4-(3-ethylamino-2- pyridinyl)-l ,4-diazepine

Follovving the general procedure of PREPARATION 6 and making non-critical variations but starting vvith l-(l,l-dimethylethoxycarbonyl)-4-(3-amino-2-pyridinyl)-l,4-diazepine (PREPARATION 51, 6.07 g), the title compound is obtained, NMR (300 MHz, CDClj) 7.65, 6.86, 6.76, 4.25 , 4.11, 3.64-3.48, 3.30-3.21, 3.12-3.08, 1.92, 1.83, 1.47, and 1.45 δ. PREPARATION 53 l-(3-EthyIamino-2-pyridinyl)-l,4-diazepine (Π)

Follovving the general procedure of PREPARATION 9 and making non-critical variations but starting vvith l-(l,l-dimethyIethoxycarbonyl)-4-(3N-ethylamino-2-pyridinyl)-1,4-diazepine (PREPARATION 52, 5.12 g), the title compound is obtained, NMR (300 MHz, CDClj) 7.66, 6.85 , 6.76, 4.17, 3.31-3.26, 3.14-3.01, 1,84 and 1.29 δ. -47- LV 10264 PREPARATION 54 l-(l,l-Dimethylethoxycarbonyl)-4-(3-(l-methylethyl)amino- 2-pyridinyl)-l,4-diazepine

Fol!owing the general procedure of PREPARATION 8 and making non-critical variationsbut starting vvith l-(l,l-dimethylethoxycarbonyl)-4-(3-amino-2-pyridinyl)-l,4-5 diazepine (PREPARATION 51, 18.13 g), the title compound is obtained, NMR (300 MHz, CDClj) 7.62, 6.85, 6.76, 4.18, 3.63-3.48, 3.28-3.19, 3.07, 1.92, 1.83, 1.46, 1.45 and 1.23 5. PREPARATION 55 l-(3-(l-Methylethyl)amino-2-pyridinyl)-l,4-diazepine (II)

Follovving the general procedure of PREPARATION 9 and making non-critical 10 variations but starting vvith l-(l,l-dimethylethoxycarbonyl)-4-(3-(l-methylethyl)-2-pyridinyl)-l,4-diazepine (PREPARATION 54, 15.08 g), the title compound is obtained, NMR (300 MHz, CDC1}) 7.61, 6.82, 6.75,4.17, 3.50, 3.28-3.22,3.06-3.01,2.67,1.83 and 1.20 5. PREPARATION 56 · Ethyl 5-(Benzyloxycarbonylamino)indole-2-carboxylate

15 Ethyl 5-aminoindole-2-carboxylate [J. Am. Chem. Soc. 80, 4621 (1958) JCS

Perkin I 53 (1977), 0.50 g] is dissolved in 49 ml of methylene chloride and pyridine (0.20 g) is added. The reaction is cooled to 0° and benzylchloroformate (0.36 ml) is added dropvvise over 10 min. The reaction is stirred for 1 hr, diluted vvith chloroform, vvashed vvith saturated aqueous sodium bicarbOnate, vvater, saline, dried over anhydrous 20 sodium sulfate and concentrated under reduced pressure. The concentrate is purified by flash column chromatography (150 g silica gel) eluting vvith hexane/ethyl acetate (3/1). The appropriate fractions are pooled and concentrated to give the title compound, NMR (300 MHz, CDClj) 8.90, 7.79, 7.41-7.33, 7.24, 7.16, 5.22, 4.40 and 1.41 5. PREPARATION 57 5-Benzyloxycarbonylaminoindole-2-carboxylic acid (I) 25 Ethyl5-Benzyloxycarbonylaminoindole-2-carboxylate, (PREPARATION56,0.76 g) is dissolved in l,4-dioxane (5.6 ml) and vvater (0.56 ml). Crushed potassium hydroxide (0.23 g) is added and the reaction is heated to 50° for 5 hr. The reaction is neutralized by adding 4.05 ml of 1 N aqueous hydrochloric acid. The reaction is extracted vvith THF/chloroform (10/90,3 x), saline, dried over anhydrous sodium sulfate 30 and concentrated under reduced pressure to give the title acid, NMR (300 MHz, d4-CD30D) 7.64, 7.34-7.15, 6.98 and 5.09 5. PREPARATION 58 l-[5-Benzyloxycarbonylaminoindolyl-2-carbonyl]-4-(3-(l- methylethyl)amino-2-pyridinyl)piperazine -48- 5-Benzy!oxycarbonylaminoindole-2-carboxylic acid (PREPARATION 57, 0.65 g), and 1 -(3-(l-methyIethyl)amino-2-pyridinyl)piperazine (0.506 g) are dissolved in 4.2 ml of THF. EDC (0.48 g) is added and the reaction is stirred for 2 h. The reaction I. mixture is diluted with chloroform, washed with saturated aqueous scxiium bicarbonate, saline, dried over anhydrous sodium sulfate and concenlrated under reduced pressure. The concentrate is purified by flash column chromatography (35 g silica gel) eluting with methanol/chloroform (5/95). The appropriate fractions are pooled and concenlrated to give the title compound, NMR (300 MHz, d4-CD30D) 7.66, 7.47, 7.31-7.14, 6.89, 6.69, 5.09, 3.93, 3.54, 2.98 and 1.17 δ. PREPARATION 60 l-[5-(2’-Benzyloxyg]ycy!amino)indolyI-2-caibonyl]-4-(3-(l- methylethyl)-amino-2-pyridinyI)piperazine l-{5-Aminoindolyl-2-carbonyl]-4-(3-(l-methylethyl)amino-2-pyridinyl)piperazine (EXAMPLE 9, 2.5 g), N-carbobenzyloxyglycine (1.52 g) and EDC (1.52 g) are stirred together at 20-25° in 13 ml of THF for 3 hr. The reaction mixture is diluted with chloroform, vvashed with saturated aqueous sodium bicarbonate, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate is purified by flash column chromatography eluting with methanol/chloroform (5/95). The appropriate fractions are pooled and concentrated to give the title compound, NMR (300 MHz, CD30D) 7.75,7.43, 7.26-7.20, 6.86,-6.69, 4.99,3.90-3.80,3.52, 2.96 and 1.11 δ. PREPARATION 61 1-Methyl 4-methoxy-a-azidocinnamate p-Methoxybenzaldehyde (5.0 g) and methyl azidoacetate (16.9 g) are dissolved in 125 ml of methanol and cooled to -10“ (ice-acetone bath). Then sodium methoxide (7.93 g, 25% in methanol) is added dropwise such that the temperature does not rise above -5°. After 2 hr the cooling bath is removed and the reaction is warmed to 20-25° while being monitored by TLC. When no starting material remained, the reaction is diluted vvith ether and saturated ammonium chloride. After extracting with ether the organic layers are washed with ammonium chloride, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate is purificed by flash column chromatography eluting vvith ethyl acetate/hexane (1/99) to ethyl acetate/hexane (10/90). The appropriate fractions are pooled and concentrated to give the title compound, NMR (300 MHz, CDC13) 7.80-7.76, 6.92-6.87, 3.88 and 3.79 3. PREPARARATION 62 Methyl 6-Methoxyindole-2-carboxylate -49- LV 10264

Toluene (185 ml) is added to methyl 4-methoxy-a-azidocinnamate (PREPARA-TION 61, 7.73 g) and the reaction is brought to reflux and maintained at reflux for 3 hr. Then the reaction is concentrated under reduced pressure and triturated with hexane. The solids are filtered and dried under reduced pressure to give the title indole, HRMS 5 Calcd. for CnH„NO,: 205.0739, found: 205.0736; NMR (300 MHz, CDC1,) 8.75,7.47, 7.11, 6.76-6.73, 3.86, and 3.79 6. PREPARATION 63 6-Methoxyindol-2-carboxylic acid (I)

Methyl 6-methoxyindole-2-carboxylate (PREPARATION 62,5.71 g) is dissolved in 70 ml of dioxane and 7 ml of water and 1.87 g of crushed potassium hydroxide are 10 added. The reaction is heated to 50° and stirred 1.5 hr, The reaction mixture is acidified to pH 4-5 and extracted several times with methanol/chloroform (10/90). The organic layers are combined and dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title acid, NMR (300 MHz, d4-CD3OD) 7.47, 7.08, 6.90, 6.72 and 3.82 δ. 15 PREPARATION 64 Methyl 4-fluoro-a-azidocinnamate

Following the general procedure of PREPARATION 61 and making non-critical variations but starting with p-fluorobenzaldehyde (5.0 g), the title compound is obtained, NMR (300 MHz, CDC13) 7.82, 7.07, 6.87 and 3.91 δ. PREPARATION 65 Methyl 6-fluoroindole-2-carboxylate 20 FolIowing the general procedure of PREPARATION 62 and making non-criu’cal variations but starting with methyl 4-fluoro-a-azidocinnamate (PREPARATION 64,7.00 g), the title compound is obtained, NMR (300 MHz, CDC13) 8.95, 7.61, 7.20, 7.08, 6.93 and 3.95 δ. PREPARATION 66 6-Fluoroindole-2-carboxylic acid (I) 25 FoIIovving the general procedure of PREPARATION 63 and making non-critical variations but starting with methyl 6-fluoroindole-2-carboxylate (PREPARATION 65, 1.77 g), the title compound is obtained, NMR (300 MHz, d4-CD3OD) 7.60, 7,13, 7.10 and 6.85 δ. PREPARATION 67 Methyl 2-methoxy-a-azidocinnamate 30 FoIIovving the general procedure of PREPARATION 61 and making non-critical variations but starting vvith 2-methoxybenzaldehyde (4.6 g), the title compound is obtained, NMR (300 MHz, CDC13) 8.18, 7.39, 7.32, 6.99, 6.87, 3.90 and 3.86 δ. PREPARARATION 68 Methyl 4-Methoxyindole-2-carboxylate -50-

Follovving the general procedure of PREPARATION 62 and making non-critical variations but starting with methyl 2-methoxy-a-azidocinnamate (PREPARATION 67, 4.56 g), the title compound is obtained, NMR (300 MHz, CDClj) 9.02, 7.34, 7.26, 7.02, 6.50, 3.95 and 3.94 5. PREPARATION 69 4-Methoxyindole-2-carboxylic acid (I)

Following the general procedure of PREPARATION 63 and making non-critical variations but starting with methyl 4-methoxyindole-2-carboxylate (PREPARATION 68, 3.16 g), the title compound is obtained, NMR (300 MHz, d4-CD3OD) 7.18, 7.16, 7.00, 6.49 and 3.92 5. PREPARATION 70 1-[I,I-DimethylethoxycarbonyI]-4-(3-(l-methylpropyl) amino-2-pyridinyl]piperazine

Follov/ing the general procedure of PREPARATION 8 and making non-critical variations but starting with l-[l,l-dimethylethoxycarbonyl]-4-[(3-amino)-2-pyridinyl)-piperazine (International Publication No. WO 88/08424, 1.0 g), 2-butanone (0.27 g) sodium cyanoborohydride (0.23 g), acetic acid (5.1 ml) and methanol, the title compound is obtained, NMR (300 MHz, CDClj) 7.68, 6.94, 6.86, 4.18, 3.56, 3.33, 3.05, 1.53, 1.47, 1.18 and 0.96 5. PREPARATION 71 l-[3-(l-Methylpropyl)amino)-2-pyridinyl]piperazine (II)

Following the general procedure of PREPARATION 9 and making non-critical variations but starting with l-[l,l-dimethylethoxycarbonyl]-4-[3-(l-methyIpropyI)amino-2-pyridinyl)piperazine (PREPARATION 70, 1.62 g), trifluoroacetic acid (5.52 g) and 10 ml of methylene chloride, the title compound is obtained, NMR (300 MHz, CDClj) 7.66, 6.87, 6.78, 4.17, 3.31, 3.06, 2.81, 1.64-1.48, 1.17 and 0.95 6. PREPARATION 72 l-[Benzyloxycarbonyl]-4-(3-(l-ethylpropylamino)-2- pyridinyl]piperazine

Following the general procedure of PREPARATION 8 and making non-critical variations but starting vvith l-[benzyloxycarbonyl]-4-[(3-amino)-2-pyridinyl]piperazine (PREPARATION 100 10.5 g), 3-pentanone (0.15 g) sodium cyanoborohydride (0.11 g), acetic acid (52.3 ml) and methanol (3.2), the title compound is obtained, NMR (300 MHz, CDC1,) 7.66,7.38-7.33, 6.90,, 6.79, 5:17, 4.21, 3.65, 3.15, 3.04, 1.66-1.46 and 0.93 5. PREPARATION 73 l-[3-(l-Ethylpropyl)amino-2-pyridinyl]piperazine (II)

FoIlowing the general procedure of PREPARATION 59 and making non-critical -51- LV 10264 variations but starting with l-[l-benzyloxycarbonyl]-4-[(3-(l-ethylpropylamino)-2--pyridinyl)piperazine (PREPARATION 72, 0.30 g), 10% palladium on carbon (30 mg) and ethyl acetate (10 ml), the title compound is obtained, NMR (300 MHz, CDClj) 7.65, 6.87, 6.78, 4.19, 3.40-3.10, 3.00-2.75, 1.64-1.49, and 0.93 6. PREPARATION 74 N,N,-Dimethyl-N-(5-methoxyindolyl-2-carbonyl)-N’-(3- nitro-2-pyridinyl)ethylenediamine

Follovving the general procedure of PREPARATION 35 and making non-critical variations but starting vvith 5-methoxyindole-2-carboxylic acid the title compound is obtained, mp 165-167°. PREPARATION 75 N,N,-Dimethyl-N-(5-fluoroindolyl-2-carbonyl)-N’-(3-nitro- 2-pyridinyl)ethylenediamine

Follovving the general procedure of PREPARATION 35 and maldng non-critical variations but employing 5-fluoroindole-2-carboxylic acid, the title compound is obtained, mp 161-162°. PREPARATION 76 7-Azaindole-2-carboxylic acid (I)

Follovving the general procedure of PREPARATION 42 and maldng non-critical variations employing 7-azaindole, the title compound is obtained, NMR (300 MHz, d6-DMSO) 12.64 , 8.44 , 8.25,7.25 and 7.18 6. PREPARATION 77 Methyl 3,4-methyIenedioxy-a-azidocinnamate

Following the general procedure of PREPARATION 61 and making non-critical variations but starting vvith piperonal (5.0 g), and methyl azido acetate (15.3 g), the title compound is obtained, NMR (300 MHz, CDC13) 7.56, 7.17, 6.84, 6.82, 6.00 and 3.90 δ. PREPARATION 78 Methyl 5,6-methylenedioxyindole-2-carboxylate

Follovving the general procedure of PREPARATION 62 and making non-critical variations but starting vvith methyl 3,4-methylenedioxy-a-azidocinnamate (PREPARATION 77, 5.38 g), the title compound is obtained, NMR (300 MHz, CDClj) 8.90, 7.08, 6.99, 6.82, 5.97 and 3.91 δ. PREPARATION 79 5,6-MethylenedioxyindoIe-2-carboxylic acid (I)

Follovving the general procedure of PREPARATION 63 and making non-critical variations but starting vvith methyl 5,6-methylenedioxyindole-2-carboxylate (PREPARATION 78, 4.77 g), potassium hydroxide (1.47 g), the title compound is obtained, C,H,N analysis calcd. for CJ0H7NO4 C, 58.54; H, 3.44; N, 6.83; found: C, 58.27; H, 3.18; -52- Ν, 6.95. PREPARATION 80 Methyl 3-bromo-4-methoxy-a-azidocinnamate

Following the general prooedure of PREPARATION 61 and making non-critical variations but slarting with 3-bromo-4-methoxybenzaldehyde (5.0 g) and methyl 5 azidoacetate (10.7 g), the title compound is obtained, NMR (300 MHz, CDClj) 8.10, 7.73, 6.89, 6.79, 3.94 and 3.90 δ. PREPARATION 81 Methyl 5-bromo-6-methoxyindole carboxylate and methyl 7-bromo-6-methoxyindolecārboxylate

Follovving the general procedure of PREPARATION 62 and making non-critical 10 variations but starting with methyl 3-bromo-4-methoxy-a-azidocinnamate (PREPARATION 80, 3.25 g), the title compounds are obtained (2.22 g of methyl 5-bromo-6-methyoxyindole carboxylate and 0.46 g of methyl 7-bromo-6-methoxyindole carboxylate). They are separated by careful chromatography (5% acetone/hexane to 20% acetone/hexane). Methyl 5-bromo-6-methox'yindole carboxylate, NMR (300 MHz, 15 CDClj) 8.87, 7.86, 7.09, 6.88 and 3.93 δ. Methyl 7-bromo-*6-methoxyindole carboxylate, NMR (300 MHz, CDC1,) 8.83, 7.58, 7.24, 6.89, 3.98 and 3.95 δ. PREPARATION 82 5-Bromo-6-methoxyindole-2-carboxylic acid (I)

Following the general procedure of PREPARATION 63 and making non-critical variations but starting with methyl 5-bromo-6-methoxyindole carboxylate (PREPA-20 RATION 81, 3.31 g) and potassium hydroxide (0.98 g), the title compound is obtained, NMR (300 MHz, CD3OD) 7.79, 7.03 , 7.01 and 3.89 δ. PREPARATION 83 7-Bromo-6-methoxyindole-2-carboxylic acid (I)

Following the general procedure of PREPARATION 63 and making non-critical variations but starting with methyl 7-bronio-6-methoxyindole carboxylate (PREPA-25 RATION 81, 0.36 g) and potassium hydroxide (0.11 g), the title compound is obtained, NMR (300 MHz, CDjOD) 7.58, 7.20, 6.96 and 3.93 δ. PREPARATION 84 Methyl 2-methyl-o-azidocinnamate

Following the general procedure of PREPARATION 61 and making non-critical variations but starting with o-to!uaIdehyde (5.0 g), methyl azidoacetate (19.2 g), the title 30 compound is obtained, NMR (300 MHz, CDC1,) 7.96, 7.26-7.18, 7.13, 3.92 and 2.36 δ. PREPARATION 85 Methyl 4-methylindole-2-carboxylate

Follovving the general procedure of PREPARATION 62 and making non-critical -53- LV 10264 variations but starting with methyl 2-methyl-a-azidocinnamate (PREPARATION 84,6.77 g), the title compound is obtained, NMR (300 MHz, CDC13) 8.93, 7.27-7.20, 6.94, 3.95 and 2.57 6. PREPARATION 86 4-Methylindole-2-carboxylic acid (I)

Follovving the general procedure of PREPARATION 63 and making non-critical variations but starting with methyl 4-methylindole-2-carboxylate (PREPARATION 85, 4.94 g), potassium hydroxide (1.75 g), the title compound is obtained, NMR (300 MHz, CDjOD) 7.24, 7.19, 7.12, 6.85 and 2.51 6. PREPARATION 87 Methyl 4-N,N-dimethylamino-ar-azidocinnamate

Follovving the general procedure of PREPARATION 61 and making non-critical variations but starting vvith 4-dimethylaminobenzaldehyde (5.0 g), methyl azido acetate (15.4 g), the title compound is obtained, NMR (300 MHz, CDClj) 7.74, 6,69, 3.88 and 3.03 5. PREPARATION 88 Methyl 6-(N,N-dimethylamino)indole-2-carboxyIate

Follovving the general procedure of PREPARATION 62 and making non-critical variations but starting vvith methyl 6-(N,N-dimethyl)amino-cr-azidocinnamate (PREPA-RATION 87, 1.46 g), the title compound is obtained, NMR (300 MHz·, CDClj) 8.70, 7.53, 7.12, 6.82, 6.69, 3.91, and 3.01 δ. PREPARATION 89 6-(N,N-Dimethylamino)indole-2-carboxylic acid (I)

Follovving the general procedure of PREPARATION 63 and making non-critical variations but starting vvith methyl 6-(N,N-dimethylamino)indole-2-carboxylate (PREPARATION 88, 0.80 g), potassium hydroxide (0.25 g), the title compound is obtained, NMR (300 MHz, CDjOD) 7.62, 7.1ā, 7.11, 7.01, and 3.11 δ. PREPARATION 90 Methyl 3-fluoro-4-methoxy-Q;-azidocinnamate

Follovving the general procedure of PREPARATION 61 and making non-critical variations but starting vvith 3-fluoro-4-methoxybenzaldehyde (5.0 g), and methylazido acetate (14.91 g), the title compound is obtained, NMR (300 MHz, CDClj) 7.75, 7,45, 6.95, 6.81,3.93, and 3.90 δ. PREPARATION 91 Methyl 5-fluoro-6-methoxyindole-2-carboxylate

Follovving the general procedure of PREPARATION 62 and making non-critical variations but starting vvith methyl 3-fIuoro-4-methoxy-a-azidocinnamate (PREPARA-ΊΊΟΝ 90, 1.31 g), the title compound is obtained, NMR (300 MHz, CDClj) 8.88,7.32, 7.12, 6.90, and 3.93 5. -54- PREPARATION 92 5-Fluoro-6-methoxyindole-2*carboxylic acid (I)

Following the general procedure of PREPARATION 63 and making non-critical variations but starting with methyl 3-fluoro-4-methoxyindole-2-carboxylate (PREPARATION 91, 1.05 g), potassium hydroxide (0.32 g), the title compound is obtained 5 (0.98 g, mp 239-240°), NMR (300 MHz, CD,OD) 7.27, 7.06, 7.03, and 3.89 δ. PREPARATION 93 Methyl 4-nitro-a-azidocinnamate

Following the general procedure of PREPARATION 61 and making non-critical variations but starting vvith p-nitrobenzaldehyde (10 g) and methyl azidoacetate (30.4 g), the title compound is obtained, NMR 8.34, 8.07, 7.02, and 4.07 δ. 10 PREPARATION 94 Methyl 6-nitroindole-2-carboxyIate

Follov/ing the general procedure of PREPARATION 62 and making non-critical variations but starting with methyl 4-nitro-or-azidocinnamate (PREPARATION 93, 6.75 g), the title compound is obtained, NMR (300 MHz, CD3OD) 8.30, 7.87, 7.72, 7.18, and 3.86 δ. 15 PREPARATION 95 6-Nitroindole-2-carboxylic acid (I)

Follovving the general procedure of PREPARATION 63 and making non-critical variations but starting with methyl 6-nitroindole-2-carboxylate (PREPARATION 94), the title compound is obtained. PREPARATION 96 Methyl-4-diethoxymethyl-a-azidocinnamate 20 Following the general procedure of PREPARATION 61 and ma^ng non-critical variations but starting with terephthaldehyde mono-(diethyl acetal), the title compound is obtained. PREPARATION 97 Methyl 6-formylindole-2-carboxylate

Following the general procedure of PREPARATION 62 and making non-critical 25 variations but starting vvith methyl-4-diethoxymethyl-a-azidocinnamate(PREPARATION 96), the title compound is obtained. PREPARATION 98 6-Formylindole-2-carboxylic acid (I)

Follovving the general procedure of PREPARATION 63 and making non-critical variations but starting vvith methyl 6-formylindole-2-carboxylate (PREPARATION 97), 30 the title compound is obtained, NMR (300 MHz, CD3OD) 9.91, 7.39, 7.69, 7.53 and 7.11 δ. PREPARATION 99 l-[Benzyloxycarbonyl]-4-[3-nitro-2-pyridinyl]pipe razine -55- LV 10264 l-(3-Nitro-2-pyridinyl)piperazine is dissolved in 175 ml of methylene chloride and cooled to 0°. Then pyridine is added follov/ed by benzylchloroformate (16.5 ml). The reaction is stirred 1.5 hr, then poured into saturated aqueous sodium bicarbonate and extracted with chloroform, dried over anhydrous sodium sulfate and concentrated in 5 vacuo to afford the title compound, NMR (300 MHz, CDC13) 8.34, 8.15, 7.38-7.32, 6.81,5.17, 3.65 and 3.45 5. PREPARATION100 l-[Benzyloxycarbonyl]-4-[3-amino-2-pyridinyl]piperazine l-[Benzyloxycarbonyl]-4-[3-nitro-2-pyridinyl]piperazine (PREPARATION 99), is dissolved in dioxane (923 ml) and cooled to 0°. Then aqueous titanium trichloride 10 (20%, 555.3 ml) is added cautious!y. After stirring 30 min the reaction is diluted with aqueous sodium hydroxide solution (2 N, 1.5 1) and filtered through celite. The filter cake is washed with methanol/chloroform (10/90). The combined organic layers are washed with water, saline, dried and concentrated in vacuo to afford the desired product, NMR (300 MHz, CDClj) 7.80, 7.38-7.32, 6.99, 6.88, 5.17, 3.67 and 3.12 5. 15 PREPARATION 101 l-[Benzyloxycarbonyl]-4-[3-(2,2,2-trifluoroacetamido)-2- pyridinyl]piperazine l-[Benzyloxycarbonyl]-4-[3-amino-2-pyridinyl]piperazine(PREPARATION100), is dissolved in 50 ml of methylene chloride and triethylamine is added. The reaction is cooled to 0° and trifluoroacetic anhydride is added dropvvise. After 30 min, the reaction 20 is poured into saturated aqueous sodium bicarbonate solution and extracted with chloroform, washed with saline, dried over anhydrous sodium sulfate and concentrated in vacuo, NMR (300 MHz, CDCl,) 8.92, 8.54, 8.22, 7.39-7.32, 7.16, 5.17, 3.70 and 3.03 δ. PREPARATION 102 1-(3-(2,2,2-Trifluoroacetamido)-2-pyridinyl]piperazine 25 l-[Benzyloxycarbonyl]-4-(3-(2,2,2-trifluoroacetamido)-2-pyridinyl]piperazine (PREPARATION 101), is dissolved in 70 ml of ethanol and 0.25 g of 10% palladium on carbon is added. The reaction is hydrogenated at 40 psi for 20 hr. Then it is filtered through a pad of celite and concentrated in vacuo to afford the title compound which is used without further purification, NMR (300 MHz, CDClj) 8.51, 8.21, 7.19, and 30 3.45-3.47 δ. PREPARATION 103 1-(3-(2,2,2-trifluoroethylamino)-2-pyridinyl]piperazine(n) 1-(3-(2,2,2-Trifluoroacetamido)-2-pyridinyl]piperazine (PREPARATION 102), is dissolved in 5 ml of tetrahydrofuran and·cooled to 0®. Then 4.84 ml of lithium -56- aluminum hydride solution is added dropvvise. After 10 min of stirring at 0®, the reaction is warmed to 20-25° and stirred 45 min. The reaction is quenched at 0° with the dropwise addition of 0.4 ml of water, 0.6 ml of 10% aquepus sodium hydroxidef and 1 ml of water. The slurry is flltered through celite, washed with 20% methanol/chloro-5 form and concentrated in vacuo to afford the title amine which is used without further purification, NMR (300 MHz, CDClj) 7.82, 6.97-6.92, 4.86, 3.75, and 3.06-3.01 δ. PREPARATION 104 l-Benzyloxycarbonyl-4-[3-(2-fluoroacetamido)-2- pyridinyl]piperazine

Following the general procedure of PREPARATION 101 and making non-critical 10 variations but starting with fluoroacetyl chloride (0.94 g), l-benzyloxycarbonyI-4-(3~ amino-2-pyridinyl]piperazine (PREPARATION 100,3.0 g), the title compound is obtained, NMR (300 MHZ, CDClj) 8.83, 8.65, 8.14, 7.38-7.32,7.12,5.17, 4.96, 3.70 and 3.07 δ. PREPARATION 105 l-[3-(2-Fluoroacetamido)-2-pyridinyl]piperazine 15 Follovving the general procedure of PREPARATION 102 and making non-critical variations but starting with l-benzyloxycarbonyI-4i[3-(2’-fluoroacetamido) -2-pyridinyl]piperazine (2.42 g), 10% palladium on carbon (0.25 g), the title compound is obtained, NMR (300 MHZ, CDClj) 8.15, 7.97, 7.00, 4.88, 4.73 and 3.13 δ. PREPARATION 106 l-[3-(2-Fluoroethylamino)-2-pyridinyl]piperazine (II) 20 Following the general procedure of PREPARATION 103 and making non-critical variations but starting with l-[3-(2-fluoroacetamido)-2-pyridinyl]piperazine(PREPARA-ΊΊΟΝ 105,1.4 g), lithium aluminum hydride (11.76 ml, 1M in tetrahydrofuran), the title compound is obtained. PREPARATION 107 1-(3-( l-Methylethylamino)-2-pyrazinyl]-l,4-diazepine (II) » 25 Follovving the general procedure of PREPARATION 24 and making non-critical variations but starting with homopiperazine (2.46 g) and 2-chloro-3-(l-methylethyl)-aminopyrazine (PREPARATION 23), the title compound is obtained, NMR (300 MHz, CDClj) 7.56, 7.34, 4.75, 4.04, 3.28-3.18, 3.00-2.94, 1.79, and 1.15 δ. PREPARATION 108 3,5-Dichloro-4-(l,l-dimethylethylamino)pyridazine 30 Follovving the general procedure of PREPARATION 31 and making non-critical variations but starting vvith t-butylamine (66.5 ml), and 3,4,5-trichloropyridazine, the title compound is obtained, NMR (300 MHz, CDClj) 8.50, 5.09, and 1.55 δ. PREPARATION 109 l-(5-Chloro-4-(l,l-dimethylethylamino)-3-pyridazinyl]- -57- LV 10264 piperazine

Following the generai procedure of PREPARATION 32 and making non-critical variations but starting with 3,5-dichIoro-4-(l,l-dimethylethylamino)pyridazine (PREPARATION 108), the title compound is obtained, NMR (300 MHz, CDC13) 8.55, 5.04, 3.25, 3.07, and 1.44 δ. PREPARATION 110 l-[4-(l, l-Dimethylethylamino)-2-pyridazinyl]piperazin(II)

Following the generai procedure of PREPARATION 28 and making non-critical variations but starting with l-[5-ch!oro-4-(l,l-dimethylethylamino)-3-pyridazinyl]-piperazine (PREPARATION 109), and triethylamine (4.6 ml), the title compound is obtained, NMR (300 MHz, CDCl3) 8.53, 6.79, 5.57, 3.55, and 1.47 δ. PREPARATION 111 Methyl 2-azido-3-(2-naphthyl)propionate

Following the generai procedure of PREPARATION 61 and making non-critical variations but starting with 2-naphthaldehyde (5.0 g), the title compound is obtained, NMR (300 MHz, CDClj) 8.28, 7.94, 7.90-7.79, 7.51, 7.07, and 3.93 δ. PREPARATION 112 Methyl benz[g]indole-2-carboxylate

Follovving the generai procedure of PREPARATION 62 and making non-critical variations but starting with methyl 2-azido-3-(2-naphthyl)propionate (PREPARATION 111,4.28 g), the title compound is obtained, NMR (300 MHz, CDC13) 9.36, 8.20, 7.92, 7.67, 7.61-7.46, 7.33 and 4.00 δ. PREPARATION 113 Benz[g]indole-2-carboxylic acid (I)

Following the generai procedure of PREPARATION 63 and making non-critical variations but starting with methyl benz[g]indole-2-carboxylate (PREPARATION 112, 3.78 g), the title compound is obtained, NMR (300 MHz, CD3OD) 8.35, 7.78, 7.54, 7.44, 7.40-7.34 and 7.17 δ. PREPARATION 114 Methyl 2-azido-3-(l-naphthyl)propionate

Following the generai procedure of PREPARATION 61 and making non-critical variations but starting with l-naphthaldehyde (4.0 g), the title compound is obtained. PREPARATION 115 Methyl benz[e]indoIe-2-carboxylate

Following the generai procedure of PREPARATION 62 and making non-critical variations but starting with methyl 2-azido-3-(l-naphthyl)propionate (PREPARATION 114, 6.54 g), the title compound is obtained, NMR (300 MHz, CDC13) 9.25, 8.23,7.89, 7.02, 7.75, 7.62-7.51, 7.51-7.40, and 3.98 δ. PREPARATION 116 Benz[e]indole-2-carboxylic acid (I) -58-

Follovving the general procedure of PREPARATION 63 and making non-critical variations but starting with methyl benz[e]indole-2-qarboxylate (PREPARATION 115, 1.28 g), the tītie compound is obtained, NMR (300 MHz, CD,OD) 8.23, 7.85, 7.70, 7.64, 7.52, and 7.39 δ. PREPARATION 117 1-[1, l-Dimethylethoxycarbonyl]-4-[3-(2-propenylamino)- 2-pyridinyl]piperazine A mixture of l-[l,l-dimethylethoxycarbonyI]-4-[3-amino-2-pyridinyl]piperazine (International Publication 88/08424, 2.78 g), 2-bromopropene (1.87 g), anhydrous potassium carbonate (3.3 g) and acetonitrile (100 ml) is refluxed for 36 hr. The mixture is cooled and then diluted with dichlororriethane and aqueous potassium carbonate solution. The phases are separated and the organic phase is washed with saline and than concentrated in vacuo. Purification by flash column chromatography (2% metha-nol/chloroform) provided of the title compound. Capillary GC analysis (HP1 column, initial temperature at 100° for 1 min, then programmed to rise 20° per minūte to 250°) gavē a peak at 6.06 (96%) minūtes. PREPARATION 118 1 -[3-(2-Propenylamino)-2-pyridinyl]piperazine (II)

Follovving the procedure of PREPARATION 7 and making non-critical variations butstartingvvith 1-(1,1-dimethyIethoxycarbonyI]-4-[3-(2-propenyl)-2-pyridinyl)piperazine (PREPARATION 117, 0.7 g), the title compound is obtained. TLC analysis (silica gel, eluent: 15% methanol/chloroform, visualization with UV light and iodine vapor) shovved one spot, Rf = 0.1. PREPARATION 119 Methyl 6-hydroxymethyIindole-2-carboxylate

Sodium borohydride is added to a solution of methyl 4-formyImethyl-a-azidoinnamate in methanol at 0°. After 30 min, the reaction is vvarmed to 20-25° and stinred for a further 30 min. Then it is cooled to 0° and quenched via the addition of vvater. The product is extracted with chloroform, dried over anhydrous sodium sulfate and concentrated in vacuo to provide the title compound. PREPARATION 120 MethyI-4-hydroxymethyl-a-azidocinnamate

Follovving the general procedure of PREPARATION 62 and making non-critical variations but starting with methyl 4-hydroxymethyl-a-azidocinnamate (PREPARATION 119), the title compound is obtained. PREPARATION 121 6-Hydroxymethylindole-2-carboxylic acid (I)

Follovving the general procedure of PREPARATION 63 and making non-critical -59- LV 10264 variations but starting with methyl 6-hydroxymethylindole-2-carboxylate (PREPARA* ΊΠΟΝ 120), the title compound is obtained. PREPARATION 122 l-[6-Methanesulfonyloxymethylindolyl-2-carbonyl]-4-[3- (l-methylethylamino)-2-pyridinyl]piperazine (III) 5 l-[6-Hydroxymethylindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (EXAMPLE 126) is dissolved in methylene chloride and cooled to 0°. Then pyridine followed by methanesulfonyl chloride are added. The reaction is stirred for 30 min, then poured into aqueous sodium bicarbonate solution and extracted with chloroform. The organic layers are dried over anhydrous sodium sulfate and 10 concentrated in vacuo to afford the title compound. PREPARATION 123 5,6*Dihydro-lH-3H-pyrrolo-[3,2,l,i,j]-[3,l]benzoxazine- l,3-dione-quinč)line-4,6-dione (I)

IndoIine-7-carboxyIic acid (G.M. Coppola, S. Palermo, J. Heterocyclic Chem, 1986, 23, 971) is dissolved in 0.5 N hydrochloric acid and phosgene is bubbled through 15 for 2 hr at 0°. The reaction is filtered and recrystallized form acetonitrile/toluene to afford the title compound, mp 234-235°. pit. m.p. 236-239° dec.] PREPARATION 124 l-(l,l-Dimethylethoxy)carbonyl-4-methylaminopiperidine

Methylamine hydrochloride (2.36 g) is dissolved in methanol (50 ml) and potassi-um hydroxide pellets (0.60 g) and N-(l,l-di-methylethoxycarbonyl)-4-piperidone are 20 added. Sodium cyanoborohydride (0.69 g) in methanol (5 ml) is added and the mixture is stirred 2 hrs. Potassium hydroxide pellets (1.96 g) are added to the mixture which is stirred 1 hr and acidified to pH 2 with 6M hydrochloric acid and concentrated. The mixture is diluted with water (50 ml) and extracted with ether (3 x 80 ml) which is discarded. The aqueous layer is basified to pH 11 with potassium hydroxide pellets, 25 saturated with sodium chloride and extracted with ether (6 x 80 ml). The combined organic extracts are dried vvith magnesium sulfate and concentrated to afford an oil which is chromatographed on silica gel vvith a methanol/chloroform gradient (5-30%). Fractions are pooled on the basis of TLC (R, = 0.13,20% methanol/chloroform) to give the title product, NMR (CDC13) 4.04, 2.79, 2.54, 2.46, 2.33, 1.88, 1.46, and 1.26 δ. 30 PREPARATION 125 l-(l,l-Dimethylethoxy)carbonyl)-4-(N-methyl-N-(3-nitro-2- pyridinyl)amifto)piperidine

Anhydrous potassium carbonate (2.71 g) and 2-chIoro-3-nitropyridine (0.93 g) are added to a solution of 1-((1,l-dimethylethoxy)carbonyl)-4-methylaminopiperidine -60- (PREPARATION 124) (1.40 g) in acetonitrile (50 ml). The mixture is stirred 21 hrours at 20-25° and additional 2-chloro-3-nitropyridine (100 mg) and acetonitrile (5 ml) are added. The mixture is stirred 2.8 day$, concentrated and dissolved in methylene chloride (175 ml) and water (50 ml). The phases are separated and the organic phase is extracted 5 with water (2 x 50 ml) and saline (40 ml) and dried over sodium sulfate. Concentration under reduced pressure affords an oil which is chromatographed on silica gel (120 g) eluting with 10% ethyl acetate/hexane. Fractions with R< = 0.29 by TLC (silica gel, 25% ethylacetate/haxane) are pooled and concentrated to give the title compound, NMR (CDC13) 8.29, 8.11, 6.68, 4.62, 4.26, 2.85, 2.67 and 1.48 δ. 10 PREPARATION 126 4-(N-methyl-N-(3-nitro-2-pyridinyI)amino)piperidine

Trifluoroacetic acid (13.0 ml) is added to a solution of l-((,ll-dimethylethoxy)-carbonyl)-4-(N-methyl-N-(3-nitro-2-pyridinyl)amino)piperidine (PREPARATION 125) in methylene chloride (100 ml) with cooling to -78°. The mixture is warmed to 20-25°, stirred 17 hrs, cooled to 0° and basified to pH 12 with 5% sodium hydroxide. The 15 phases are separated and the aqueous phase is extracted with methylene chloride (2 x 50 ml). The combined organic phases are dried over sodium sulfate and concentrated to give the title compound, mp 115.5-117°. PREPARATION 127 l-(indolyl-2-carbonyl)-4-(N-methyl-N-(3-nitro-2-pyridinyl)- amino)piperidine (II) 20 Following the general procedure of PREPARATION 35 and making non-critical variations but starting with 4-(N-methyl-N-(3-nitro-2-pyridinyl)amino)piperidine (PREPARATION 126) the title compound is obtained, mp 228-229.5°. PREPARATION 128 5-Azaindole-2-carboxylic acid

Follovving the general procedure of PREPARATION 42 and making non-critical 25 variations employing 5-azaindoIe, the title compound is obtained. PREPARATION 129 l-[5-Fluoroindolyl-2-carbonyl]-4-[3-amino-2-pyridinyl]- piperazine

Following the general procedure of PREPARATION 22 and making non-critical variations but starting with l-[5-fluoroindolyl-2-carbonyl]-4-[3-nitro-2-pyridinyl]-30 piperazine (PREPARATION 17), the title compound is obtained. EXAMPLE1 l-[4-Methoxy-3,5-dimethylben2oyl]-4-[3-(ethylamino)-2-pyridinyl]-piperazine (IV) 3,5-Dimethyl-4-methoxybenzoic acid (I, PREPARATION 3, 0.36 g) is added to -61- LV 10264 a solution of l,r-carbonyldiimidazole (0.33 g) in tetrahydrofuran (4 ml) at 20-25°. After one hour of stirring, 4-(3-(ethylamino)-2-pyridinyl]piperazine (II, International Publication No WO 87/01706 based on International Patent application No PCT/US86/-01797, PREPARATION A-47, 0.42 g) in tetrahydrofuran (6 ml) is'added and the 5 solution is stirred for 18 hours. The mixture is diluted with dichloromethane and a saturated aqueous sodium bicarbonate solution. The phases are separated, the organic phase is washed with water, then with saline and the phases are separated. The organic phase is dried over sodium sulfate and concentrated under reduced pressure to give an oil. The oil is flash chromatographed on silica gel (230-400 mesh), the product eluted 10 with chloroform, the appropriate fractions are pooled and concentrated to give the title compound.

The title compound is treated with ethereal hydrochloric acid, and the resulting oil is solidified by dissolving in acetone (6 ml) and adding drop by drop to ether (500 ml). The solid precipitate is collected and dried in a vacuum oven at 70° to give the 15 hydrochloride salt of the title compound, analysis calcd for C^Hj^Oj.eHG^HjO (C, 64.45; H, 7.40; N, 14.31; Cl, 5.44) found C, 64.62; H, 7.45; N, 14.49; Cl, 5.33. EXAMPLE 3 l-[4-Methoxy-3,5-dimethylbenzyl]-4-[3-(ethylamino)-2-pyridin-yl]piperazine (IV)

FoIlowing the general procedure of EXAMPLE 1 and making non-critical 20 variations but starting with 3,5-dimethyl-4*methoxybenzyl chloride (I, PREPARATION 4, 3.70 g), the title compound is obtained.

Follov/ing the general procedure of EXAMPLE 1 and making non-critical variations the title compound is converted to its hydrochloride salt which is recrystallized from a methanol/ether mixture, mp. 214-216°. 25 EXAMPLE 4 l-[4-Hydroxy-3,5-dimethyIbenzyl]-4-[3-(ethylamino)-2-pyridin- yl]piperazine (IV) . *

Follov/ing the general procedure of EXAMPLE 1 and making non-critical variations but starting with 3,5-dimethyl-4-hydroxybenzyl chloride (I, PREPARATION 5, 1.6 g), the title compound is obtained. ' 30 Following the general procedure of EXAMPLE 1 and making non-critical variations the title compound is converted to its hydroch!oride salt which is recrystallized from methanol/ether, mp. 203-206°. EXAMPLE 5 i-[4-Methoxy-3,5-dimethylbenzyl]-4-[3-(propylamino)-2-pyridinyl]- -62- piperazine (IV)

FoIlowing the general procedure of EXAMPLE -1 and making non-critical variations but starting with 3,5-dimethyI-4-methoxybenzyI chloride (I, PREPARATION 4, 0.41 g) and l-[3-(propylamino)-2-pyridinyl]piperazine (II, PREPARATION 7, 0.42 5 g), the title compound is obtained.

Following the general procedure of EXAMPLE 1 and making non-critical variations, the hydrochloride salt of the title compound is obtained, which is recrystal-Iized from acetone/ether, mp 223-225°. EXAMPLE 7 1 -[4-Methoxybenzyl]-4-[3-(ethylamino)-2-pyridinyl]piperazin(IV) 10 A solution of l-[4-Methoxyphenyl-l-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]- piperazine (III, PREPARATION 18,1.5 g) in tetrahydrofuran (20 ml) is added dropwise to a suspension of lithium aluminum hydride (0.35 g) in tetrahydrofuran (15 ml) at 20-25°. The mixture is stirred for 20 hours. The reaction is quenched by sequential addition of water (0.35 ml), aqueous sodium hydroxide (15%, 0.35 ml) and water (1.05 15 ml). The mixture is filtered, and the filtrate is concentrated under reduced pressure to an oil. The oil is flash chromatographed on silica gel, eluting with chloroform. The ap-propriate fractions are pooled and concentrated to give the title compound.

The hydrochloride salt of the title compound is prepared by dissolving the title compound in ether and treating it with ethereal hydrogen chloride. The salt is recrys-20 tallized from acetone/ether, mp. 189-190°; MS (high resolution) calculated for Ο,,ΗμΝΑ (326.2106), found 326.2106. EXAMPLE 10 l-[Indolyl-2-carbonyl]-4-[2-ethoxyphenyl]piperazine(X) l,r-carbonyldiimidazole (1.30 g) is added to a 20-25° solution of indole-2-carboxylic acid (I, 1.17 g) in tetrahydrofuran (14 ml). After one hour of stirring, the 25 reaction is cooled to 0° and a solution of l-(2-ethoxyphenyl)piperazine (II, 1.50 g) in tetrahydrofuran (7 ml) is added via cannula. After 30 minūtes at 0°, the reaction is warmed to 20-25° and stirred 18 hours. Ddichloromethane (100 ml) is added and the mixture is washed with saturated aqueous sodium bicarbonate, dried over anyhydrous sodium sulfate and concentrated under reduced pressure. The residue is purified by flash 30 column chromatography (2 cm x 20 cm) eluting with 100% chloroform. The appropriate fractions are pooled and concentrated to give the title compound.

The title compound is dissolved in methanol and treated with ethereal hydroch!o-ric acid. The precipitated salt is recrystallized from ether/methanol to give the -63- LV 10264 hydrochloride salt of the title compound, mp. 205-208°. EXAMPLE 11 l-[Indolyl*2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]pipera2ine

GiD l,r-Carbonyldiimidazole (0.825 g) is added to a 20-25° solution of indole-2-5 carboxylic acid (1. 0.78 g) in tetrahydrofuran (10 ml), After one hour of stirring, l-(3-ethylamino-2-pyridinyI)piperazine GI» 1-0 g) in tetrahydrofuran (5 ml) is added via cannula at 0°. After 15 minūtes at 0°, the reaction is warmed to 20-25° and stirred 20 hours. It is then diluted with ether (75 ml), washed with saline (75 ml), and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue is 10 purified by flash column chromatography (2 cm x 20 cm) eluting with methanol/-chloroform (2/98). The appropriate fractions are pooled and concentrated. The solid is further purified by recrystaIIization (ethyl acetate/hexane) to give the title compound, mp. 138-139°.

The title compound is dissolved in methanol and treated with ethereal hydrochlo-15 ric acid. The precipitated salt is recry$tallized from ether/methanol to give the hydrochloride salt of the title compound, mp 218-219°. EXAMPLE 12 l-[5-Methoxyindolyl-2-cart>onyl]-4-[2-ethoxyphenyl]piperazine (TV) l,r-CarbonyIdiimidazole (1.30 g) is added to a 20-25° solution of 5-methoxy-indole-2-carboxylic acid (1,1.39) in tetrahydrofuran (14 ml). The reaction is stirred one 20 hour, then cooled to 0° and l-(2-ethoxyphenyl)piperazine (II, 1.50 g) dissolved in tetra-hydrofuran (7 ml) is added via cannula. The reaction is vvarmed to 20-25° and stirred 48 hours. The reaction is diluted vvith ether (100 ml), poured into saturated aqueous sodium bicarbonate (100 ml). The organic layers are separated and washed with saline (100 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. 25 The residue is recrystallized from toluene to give the title compound, mp. 105-107°. EXAMPLE 16 l-[5-Methoxyindolyl-2-carbonyl]-4-(3-(ethylamino)-2- pyridinyl]piperazine (IV) l,r-Carbonyldiimidazole (0.55 g) is added to a 20-25° solution of 5-methoxy-indole-2-carboxylic acid G» 0.59 g) in tetrahydrofuran (7.0 ml). After stirring 1 hour, 30 the reaction is transferred via cannnula into a solution of I-(3-N-ethylamino-2-pyridinyl)-piperazine (Π, 0.70 g) in tetrahydrofuran (7 ml) at -12° (ice/acetone bath). The reaction is stirred at -10° for 30 minūtes, then slowly vvarmed to 20-25° and stirred a further 18 hours. After diluting vvith ether (60 ml), the mixture is washed with saturated aqueous -64* sodium bicarbonate (70 ml), saline (70 ml) and dried over anhydrous sodium sulfate. The mixture is concentrated under reduced pressure to a residue which is purified by flash chromatography (2 cm x 20 cm) eluting with methanol/chloroform (2/98) to give the title compound, mp 153-154°. EXAMPLE 16A 1 -(5 -Methoxyindolyl-2-carbonyI]-4-[3-(ethyIamino)-2-pyridinyi]- piperazine, hydrochloride (IV) l-(Ethyl)-3-(dimethylaminopropyl)carbodiimide(1.25 g) is added to a solution of l-(3-ethyl-2-pyridinyl)piperazine (1.12 g) in THF (15 ml). The reaction is stirred at 20-25° for 3 hr, then it is dissolved in chloroform (50 ml) and extracted with saturated aqueous sodium bicarbonate, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography (200 g silica) eluting with ethyl acetate/hexane (50/50), the appropriate fractions are pooled and concentrated to give the title compound, The product is dissolved in methanol (150 ml) with heating, cooled to 20-25° and chlorotrimethylsilane (4.70 mmol) is added. The mixture is concentrated to half-volume, ether is added until cloudy and the flask is stored at 0° ovemight. Filtration gives the hydrochloride salt, mp 194-195°. CMR (300MHz, CDClj) 165.2, 155.9, 146.1, 144.8, 133.4, 130.5, 128.9, 125.6, 122.6, 116.7, 113.9, 106.5, 103.3, 56.3, 39.1 and 14.2 5.

The mesylate salt is formed by dissolving the free base in methanol and methanesulfonic acid (1 eq) is added. The solution is diluted with diethyl ether until the salt crystallizes out of solution. The crystals are collected and dried to afford the mesyl salt of the title compound, mp 215-216°, CMR (300 MHz, CD3OD) 165.22, 156.03, 146.23,141.75,133.35,130.6, 129.0,125.7,123.5, 122.5,166.6,113.9,106.5,103.2, 56.2, 45.7, 39.7, 39.0 and 14.1 5. EXAMPLE17 l-[Indolyl-2-carbonyI]-4-[3-(l-methylethylamino)-2-pyridinyl]- piperazine (III)

Following the general procedure of EXAMPLE 1 and making non-critical variations but starting with indole-2-carboxy!ic acid (I) and l-[3-(l-methyIethylamino)-2-pyridinyl]piperazine (II, PREPARATION 9, 0.19 g), the title compound is obtained, mp 151-152°. EXAMPLE 19 l-[Indolyl-2-carbonyl]-4-[3-(N,N-diethylamino)-2-pyridinyl]- piperazine flll)

l-[Indolyl-2-carbonyl]-4-(3*amino-2-pyridinyl)piperazine (ΠΙ, PREPARATION -65- LV 10264 22, 0.10 g) is dissolved in methanol (2.5 ml) and cooled to 0°. AcetaJdehyde (0.041 g) and acetic acid (5 drops) are added. After 15 minūtes of stirnng sodium cyanoboro-hydride (0.04 g) is added. The reaction is slowly warmed to 20-25° and acetaldehyde is added at 1 hour intervāls (5 x 0.041 g). Stirnng is continued 18 hours at 20-25°. 5 Then the reaction is diluted with dichloromethane (20 ml), washed with saturated aqueous sodium bicarbonate (20 ml) and saline (20 ml). The organic layer is dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography (methy!ene chloride), pooling the appropriate fractions and concentrating them give the title compound, mp 173-174°; MS (m/e) 378, 377, 348, 10 205, 204, 178, 176, 162 and 144. EXAMPLE 20 l-[Indolyl-2-methyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine (III)

Lithium aluminum hydride (0.011 g) is added to ether (1 ml) at 0°. l-(2-Indolylcarbonyl)-4-(3-(ethylamino-2-pyridinyl)piperazine(III, EXAMPLE 11,0.10 g) is 15 added portionwise. After the addition is complete the reaction is stirred at 20-25° for 18 hours. The reaction is quenched at 0° by the dropwise addition of water (0.2 ml), aqueous sodium hydroxide (15%, 0.1 ml), and water (9.5 ml). The resulting slurry is filtered through a pad of celite and sodium sulfate and concentrated under reduced pressure. The concentrate is purified by flash column chromatography (8 g silica gel), 20 eluting with ethyl acetate/hexane (1/1). The appropriate fractions are pooled and concentrated to give the title compound, NMR (300 MHz, CDCI3) 8.68, 7.71, 7.56, 7.35, 7.15, 7.08, 6.90, 6[.80, 6.38, 4.16, 3.10, 2.65 and 1.29 3. EXAMPLE 21 l-[5-Fluoroindolyl-2-carbonyl]-4-[3-(propylamino)-2-pyridinyl]- piperazine (III) 25 1,1 ’-carbonyldiimidazole (0.48) is added to a 20-25 ° solution of 5-fluoroindole-2- caiboxylic acid (I, 0.53 g) in THF (6 ml). After 1 hour of stirnng the above reaction is added dropwise via cannula to a solution of [3-(propylamino)-2-pyridinyl]piperazine (Π, PREPARATION 7, 0.72 g) in THF (6 ml) at -10° (ice/acetone bath). The reaction is stirred for 30 minūtes at -10°, s!owly warming to 20-25°, and stirred 4 hours. The 30 reaction is diluted with dichloromethane (50 ml), washed with saturated aqueous sodium bicarbonate (40 ml), saline (40 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate is purified by flash column chromatography (40 g silica gel) eluting with ethyl acetate/hexane (1/1). The appropriate fractions are -66- pooled and concentrated to give the title compound, mp 196-198°; IR (mineral oil) 3200,2920-3000,1630 and 1424 enr1; NMR (300 MHz, CDClj) 9.82,7.72,7.35,7.27, 7.03, 6.95, 6.86, 6.78, 4.32, 4.09, 3.21, 3.08, 1.71 and 1.05 δ; CMR (300 MHz, CDClj) 162.3, 159.5, 149.7, 137.4, 135.1, 132.3, 130.7, 127.5, 127.4, 120.4, 116.3, 113.4, 112.9, 112.7,112.5, 106.1, 105.8, 105.1, 105.0, 49.0, 45.2, 22.5 and 11.6 5; MS (m/e) 382, 381, 190, 176, 164, 162, 134 and 120. EXAMPLE 22 l-[5-Chloroindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]-piprazine (III) l,r-carbonyldiimidazole (0.42 g) is added to a20-25° solution of 5-chloroindole-2-carboxylic acid (1, 0.5 g) in THF (5 ml). After 1 hour of stirring at 20-25°, the above reaction is added dropwise over 10 minūtes via cannula to a -10° (ice/acetone bath) solution of [3-(ethylamino)-2-pyridinyl]piperazine (II, 0.58 g) in THF (5 ml). After 30 minūtes of stirring at -10°, the reaction is vvarmed to 20-25° and stirring is continued for 5 hours. The reaction is diluted with dichloromethane (50 ml), vvashed with saturated aqueous sodium bicarbonate (40 ml), water (40 ml) and saline (40 ml). The organic layers are dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate is purified by flash column chromatography (50 g silica gel), eluting with ethyl acetate/hexane (1/1). The appropriate fractions are pooled and concentrated to give the title compound, mp 208-209°; IR (mineral oil) 3200, 2920-3000, 1632, and 1425 cm*1; NMR (300 MHz, CDClj) 9.77, 7.72, 7.60, 7.36, 7.22 , 6.97, 6.86, 6.75, 4.23, 4.09, 3.23-3.15, and 1.33 δ; MS (m/e) 383, 178, 176, 162, 150, 148, 137, 134, and 120. EXAMPLE 23 1 -[5-Fluoroindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]- piperazine (III) l,r-carbonyldiimidazole (0.55 g) is added to a 20-25° solution of 5-fluoroindole-2-carboxylic acid (I, 0.55 g) in THF (7 ml). After 1 hour the above reaction is added dropvvise via cannula over 10 minūtes to a -12° (ice/acetone bath) solution of [3* ethy!amine)-2-pyridinyl)]piperazine (0.70 g) in THF (7 ml). The reaction is stirred 30 minūtes at -12° and then slowly allowed to warm to 20-25°. After 18 hours of stirring, the reaction is diluted with ether (50 ml), vvashed with saturated aqueous sodium bicarbonate (50 ml), saline (50 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure, The concentrate is purified by flash column chromatography (4 cm column), eluting with methanol/chloroform (5/95). The appropriate fractions are -67- LV 10264 pooled and concentrated to give the title compound, mp 187rl88°, EXAMPLE 24 l-[5-Ethylindolyl-2-carbonyl)-4-[3-(ethylamino)-2-pyridinyl]-piperazine (ΪΙΙ) l,r-carbonyldiimidazole (0.43 g) is added to a 20-25° solution of 5-ethylindoIe-5 2-carboxylic acid G, 0.5 g) in THF (5 ml). After 1 hour the above reaction is added via cannula over 10 minūtes to a -10° solution of [3-ethylamino-2-pyridinyl]piperazine GI* 0.56 g) in THF (5 ml). The reaction is slowly allowed to warm to 20-25° and stirred 5 hours. The reaction is diluted with dichloromethane (30 ml), vvashed with saturated aqueous sodium bicarbonate (40 ml), vvater (40 ml) and saline (40 ml). The organic 10 layer is dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate is purified by flash column chromatography (50 g silica gel), eluting with ethy! acetate/hexane (1/2). The appropriate fractions are pooled and concentrated to give the title compound, mp 174-176°; IR (mineral oil) 3371, 2920-3000, 1609, and 1536 cm·1; NMR (300 MHz, CDC1,) 9.23, 7.72, 7.45, 7.35, 7.15, 6.96, 6.86, 6.76, 15 4.23, 4.08, 3.22-3.19, 2.74, 1.33, and 1.28 5; MS (m/e) 378, 377,176, 172,163,162, 150, 148, and 137, EXAMPLE 25 l-[5-Fluoroindolyl-2-carbonyl]-4*[3-(l-methylethylamino)-2-pyridinyl]piperazine GH) l,r-carbonyldiimidazole (0.147 g) is added to a 20-25° solution of 5-fluoro-20 indole-2-carboxylic acid G, 0.163 g) in THF (2.5 ml). After 1 hour of stirring at 20-25°, the reaction is cooled to 0° and (3-(l-methylethylamino)-2-pyridinyl]piperazineGI, PREPARATION 9, 0.20 g) dissolved in THF (0.75 ml) is added. The reaction is allowed to warm to 20-25° and stirred for 18 hours. Then the reaction is diluted with methylene chloride (15 ml) and washed with saturated aqueous sodium bicarbonate (15 25 ml), water (15 ml) and saline (15 ml). The organic layer is dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the desired product. The product is purified by flash column chfomatography (8 g silica gel), eluting with hexane/ethyl acetate (2/1). The appropriate fractions are pooled and concentrated to give the title compound, mp 201-203°. 30 EXAMPLE 26 l-[5-Methoxyindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine GV) l,r-carbonyldiimidazole (0.147 g) is added to a room temperature solution of 5-methoxyindole-2-carboxylic acid (I, 0.174 g) in THF (3.6 ml). After stirring for 1 hour -68- at 20-25*, the reaction is cooled to 0° and [3-(l-methylethylamino)-2*pyridinyl]-piperazine (II, PREPARATION 9, 0.20) dissolved in THF (0.75 ml) is added. The reaction is allowed to warm to 20-25° and stirred 18 hours. Then the reaction is diluted with methylene chloride (15 ml) and washed with saturated aqueous sodium bicarbonate (15 ml), water (15 ml) and saline (15 ml). The organic layer is dried over anhydrous sodium sulfate and concentrated under reduced pressure to a concentrate. The concentrate is purified by flash column chromatography (8 g silica gel), eluting vvith hexane/ethyl acetate (2/1). The appropriate fractions are pooled and concentrated to give the title compound, mp 167-168*. EXAMPLE 27 l-[BenzofuroyI-2-caibonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine m

Following the general procedure of EXAMPLE 16 and making non-critical variations but using benzofuran-2-carboxylic acid G» 0.5 g), the title compound is obtained, MS (high.resolution) calculated for C20HaN4O2 (350.1743), found 350.1747. EXAMPLE 28 1 -[5-Methoxyindolyl-2-carbonyl]-4-[2-(ethylamino)phenyl]· piperazine (IV)

Follovving the general procedure of EXAMPLE 16 and maldng non-critical variations but using l-(2-ethylaminophenyl)piperazine(II, PREPARATION 15,0.881 g), the title compound is obtained, mp 190°; HRMS = 378.2061 (Calcd. for CnH26N402 is 378.2056). EXAMPLE 29 l-[Indolyl-2-carbonyl]-4-[2-(ethyIamino)phenyI]piperazine GH)

Follovving the general procedure of EXAMPLE 16 and maldng non-critical variations but using indole-2-carboxylic acid Gt 0.75 g) and l-(2-ethylaminophenyI)-piperazine GI> PREPARATION 15, 1.06 g), the title compound is obtained, mp 184-185°; HRMS = 348.1948 (Calcd for C21H24N40 is 348.1950). EXAMPLE 31 I -[Indolyl*2-carbonylJ-4-[3-(cyclopropylmethyIamino)-2- pyridinyl]piperazine (III) l-Pndolyl-2-carbonyl]-4-(3-amino-2-pyridinyl)piperazine (PREPARATION 22, 0.12 g) is dissolved in methanol (2 ml) and cyclopropylcarboxaldehyde (0.028 ml) is added. The reaction mixture is cooled to 0° and 5 drops of acetic acid are added. After 15 min, sodium cyanoborohydride (0.026 g) is addedand the reaction mixture is allovved to vvarm to 20-25°. After 3 hr, the reaction is diluted vvith methylene chloride, vvashed vvith saturated aqueous sodium bicarbonate, dried over sodium sulfate and concentrated -69- LV 10264 under reduced pressure. The concentrate is pruified by flash chromatography eluting vvith ethyl acetate/hexane (25/75). The appropriate fractions are pooled and concentrated to give the title compound, mp 157-158°. EXAMPLE 32 l-[5-Fluoroindolyl-2-methyl]-4-[3-(l-methylethylamino)-2-pyridin-yl]piperazine (III)

Following the general procedure of EXAMPLE 20 and making non-critical variations but starting with l-[(5-fTuoroindolyl)carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine GH. EXAMPLE 25), the title compound is obtained. EXAMPLE 33 l-[Indolyl-2-carbonyl]-4-[3-(2,2,2-trifluoroethylamino)-2-pyr-idinyl]piperazine (III)

Follovving the general procedure of EXAMPLE 16A and making non-critical variations but starting vvith 5-fluoroindole-2-carboxyIic acid and l-[3-(2,2,2-triflu-oroethylamino)-2-pyridinyl]piperazine (PREPARATION 103), the title compound is obtained. EXAMPLE 34 l-[5-Fluoroindolyl-2-carbonyl]-4-[3-(2,2,2-trifluoroethylamino)~ 2-pyridinyl]piperazine (III)

Follovving the general procedure of EXAMPLE 16A and making non-critical variations but starting vvith 5-fluoroindole-2-carboxylic acid and l-[3,-(2,2,2-trifluo-roethylamino)-2-pyridinyl]piperazine (PREPARATION 103), the title compound is obtained, NMR (300 MHz, CDClj) 9.35,7.87, 7.45, 7.27, 7.19-6.97,6.77, 5.05,4.11, 3.83, and 3.30 δ. EXAMPLE 35 l-[5-Benzyloxyindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]- piperazine (III)

Follovving the general procedure of EXAMPLE 16 and making non-critical variations but starting vvith 5-benzyloxyindo!e-2-carboxylicacid (l.Og), l-(3-ethylamino--2-pyridinyl)piperazine (International Publication WO 87/01706, 0.81 g), Ι,Γ-carbo-nyldiimidazole (0.61 g) and THF (7 ml), the title compound is obtained, mp 192-193°. EXAMPLE 36 l-[5-Benzyloxyindolyl-2-carbonyl]-4-[3-(l-methylethyl)amino-2- pyridinyl]piperazine GH) 5-Benzy!oxyindole-2-carboxylicacid (131 mg) and l,r-carbonyldiimidazole (96 mg) are dissolved in dry THF (2 ml) and stirred for 2 hr at 20-25°. The resulting solution is added via canula to a -10° cooled solution of l-[3-(l-methylethyl)amino-2-pyridinyl]piperazine (PREPARATON 9, 121 mg) in dry THF (2 ml). The reaction -70- mixture is then allowed to reach 20-25° ovemight. The reaction mixture is then diluted with ethyl acetate, washed with saturated sodium bicarbonate and water, dried over magnesium sulfate, and concentrated to give an oil. Purification of this oil on a silica gel flash column eluting with hexane/ethyl acetate (l/l)r the appropriate fractions are 5 pooled and concentrated to give the title compound. RecrystaIlization from ethyl ace-tate/methylene chloride gives the purified title compound, mp 147-148°. EXAMPLE 37 l-[5-Hydroxyindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]-piperazine (IV) l-[5-Benzyloxycarbony!indolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]-10 piperazine (EXAMPLE 35, 0.25 g) is dissolved in methanol (30 ml) and then palladium on carbon (10%, 0.10 mg) and ammonium formate (0.05 g) are added. The reaction is stirred at 20-25° for 4 hr and then filtered through celite and concentrated. Then the reaction is dissolved in methanol/chloroform (10/90) and washed with water (2 x), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The product 15 is purified by recrystallization from ethyl acetate/hexane to give the title compound, mp 216-217°. EXAMPLE 38 Ί -[5-Hydroxyindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl)piperazine (IV)

Follosving the general procedure of EXAMPLE 37 and making non-critical 20 variations but starting with 1 -(5-benzyloxyindolyl-2-carbonyl]r4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (EXAMPLE 36), the title compound is obtained, mp 254-257°. EXAMPLE 39 l-[Indolyl-2-methyJ]-4-[3-(l-methylethylamino)-2-pyridinyl]-piperazine (III)

Following the general procedure of EXAMPLE 20 and making non-critical 25 variationsbutstartingwithl-[indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]-piperazine (III, EXAMPLE 17), the title compound is obtained. EXAMPLE 42 1 -[5-Methoxy-4,6,7-trimethylindolyI-2-cart»onyl]-4-[3-(ethylamino)- 2-pyridinyI]piperazine (IV)

Following the general procedure of EXAMPLES 1 and 16 and making non-30 critical variations but starting vvith 5-methoxy-4,6,7-trimethylindole -2-carboxylic acid (I, PREPARATION 20), the title compound is obtained, mp 166-168°. EXAMPLE 44 l-[Indolyl-2-carbonyl]-4-[3-(l,l-dimethylethylamino)-2-pyridinyl]-piperazine (III) -71- LV 10264 l-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (45 mg) is added to a 20-25° solution of indole-2-carboxylic acid (35 mg) and l-[3-(l,l-dimethylethyl-amino)-2-pyridinyl]piperazine (PREPARATION 21, 50 mg) in tetrahydrofuran (3 ml). After stirring 1 hr, the solution is diluted with water and extracted with methylene chloride (3 x). The combined extracts are washed with saline, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting solid is flash chromatographed (silica gel, 230-400 mesh), eluting with methanol/methylene chloride (1/25); the appropriate fractions are pooled and concentrated to give the title compound, as an oil. The PMR, CMR, IR, and mass (M+ 377) spectra support the desired compound.

The title compound is dissolved in methanol and treated with ethereal hydrochloric acid. The precipitated salt is collected by filtration and dried in vacuo to give the hydrochloride salt of the title compound, mp 175-190°. EXAMPLE 45 . l-[5-Methoxyindolyl-2-carbonyl]-4-[3-(l,l-dimethylethylamino)-2- pyridiny!]piperazine hydrochloride salt GV)

Following the general procedure of EXAMPLE 44 and making non-critical variations but starting with 5-methoxyindole-2-carboxylic acid (204 mg), l-(ethyl)-3-(di-methylaminopropyl)carbodiimide (224 mg), the title compound is obtained, mp 119-121°; MS (m/e) 407. EXAMPLE 46 l-[5-Fluoroindolyl-2-carbonyl]-4-[3-(l, l-dimethylethylamino)- 2pyridinyl]piperazine hydrochloride salt G^)

Following the general procedure of EXAMPLE 44 and making non-critical variations but starting with 5-fluoroindole-2-carboxylic acid (88 mg), the title compound is obtained, mp 168-178°; MS (m/e) 395. EXAMPLE 47 l-(5-Fluoroindolyl-2-carbonyl)-4-[3-(l-methylethyIamino)-2- pyrazinyl]piperazine (III)

Follovving the general procedure of EXAMPLE 16 and making non critical variations but starting vvith indole-2-carboxyIic acid (0.215 g), l,r-carbonyldiimidazole (.20 g) and l-[2-(l-methylethylamino-3-pyrazinyl]piperazine (PREPARATION 25, 0.32 g) in THF (5 ml). The product is chromatographed eluting with methanol/chloroform (1/99). The appropriate fractions are pooled and concentrated to give the title compound.

The title compound is treated vvith ethereal hydrochloric acid, the hydrochloride -72- saJt is recrystallized from methanol/ether to give salt of the title compound, mp 251-252°. EXAMPLE 48 l-(5-Fluoroindolyl-2-carbonyl)-4-[5-(l-methylethylamino)-4- pyrimidinyl]piperazine (III)

Follovving the general procedure of EXAMPLE .16 and making non-critical variations but starting with 5-fluoroindole-2-carboxyiic acid (0.179 g) and 1-(5-(1-methylethylamino)-4-pyrimidinyl]piperazine (PREPARATION 30, 0.24 g), the title compound is obtained.

The free amine is treated with ethereal hydrochloric acid. The hydroch!oride salt is recrystallized from ethanol/ether to give the salt of the title compound, mp 288-289°. EXAMPLE 49 1 -(Indolyl-2-carbonyl)-4-[4-( 1 -methylethylamino)-3-pyridazinyl] piperazine, methane sulfonate (III)

Following the general procedure of,EXAMPLE 16 and making non-critical variations but starting with indole-2-carboxylic acid (0.48 g) and 1-(4-( 1 -methylethyl-amino)-3-pyridazinyl]piperazine (PREPARATION 33), the title compound is obtained. i

The free base is treated with and ethanolic solution of methanesulfonic acid (.21 g) and recrystallized from ethanol/ethyl acetate to give the salt of the title compound, mp foams at 130-145° then melts at 182-185°. EXAMPLE 50 l-(5-FIuoroindoIyI-2-carbonyI)-4-(4-(l-methyIethyl)amino)-3- pyridazinyl]piperazine, methane sulfonate (III)

Follovving the general procedure of EXAMPLE 16 and making non-critical variations but starting with 5-fluoroindole-2-carboxylic acid (0.53 g) and 1-(4-(1-methylethylamino)-3-pyridaziny!]piperazine (PREPARATION 33, 3.0 mmol), a solid is obtained vvhich is recrystallized from ethyl acetate to give the title compound.

The free base is treated vvith and ethanolic solution of methanesulfonic acid (.21 g) and recrystallized from ethanol to give the salt of the title compound, mp 215-217. EXAMPLE 51 l-[5-Fluoroindolyl-2-carbony!]-4-[3-(l,l*dimethylamino)-2-pyrazin- yl]piperazine (III), methane sulfonate

Follovving the general procedure of EXAMPLE 16 and making non-critical variations but starting vvith 5-fluoroindole-2-parboxylic acid (0.44 g) and (2.50 mmol), a solid is obtained vvhich is recrystallized from ethyl acetate to give the title compound.

The free base (0.5 g) is treated vvith and ethanolic solution of methanesulfonic acid (.13 g) and recrystallized from ethanol/ethyl acetate/hexane to give the salt of the -73- LV 10264 ι· title compound, mp softens at 130-155, then melts at 175°. EXAMPLE 52 N,N’-Dimethyl-N-(indolyl-2-carbon;yl)-N,-(3-(l-methylethyl-amino)pyrid-2-yl)ethylenediamine (III)

Palladium black (100 mg) is added to a solution of N,N’-dimethyl-N-(indolyl-2-5 carbonyI-N,-(3-nitro-2-pyridinyI)ethyIendiamine (PREPARATION 35, 150 mg) in methanol (20 ml) and acetone (10 ml). The mixture is stirred one hour under a hydrogen atmosphere (balloon), filtered and concentrated. The residue is dissolved in methanol (4 ml) and acetone (1 ml) and treated with sodium cyanoborohydride (31 mg) and enough acetic acid to give pH 5 on moistened indicator paper. The mixture is 10 stirred 5.25 hr at 20-25°, concentrated to dryness and partitioned between methylene chloride (30 ml) and saturated potassium carbonate (10 ml). The phases are separated, the organic phase is extracted with the base (10 ml) and dried over sodium sulfate. Removal of solvent under reduced pressure gives the crude product. The crude product is chromatographed on a bed of silica gel (40 ml) eluting with ethyl acetate/hexane 15 (50/50), pooling and concentrating the appropriate fractions on the basis of TLC (ethyl acetate/silica gel) gives the title compound; NMR (CDClj) 9.97, 7.71, 7.63, 7.44,7.26, 7.12, 6.90, 6.85, 6.78, 4.25, 3.82, 2.74, and 1.13 δ. EXAMPLE 53 N,N’-Dimethyl-N-(indolyl-2-carbonyl)-N’-[3-(l-methylethyl- amino)-2-pyridyl]-1,3-propanediamine (III)

20 Follovving the general procedure of PREPARATIONS 34 and 35, and EXAMPLE 52, making non-critical variations but starting with N,N’-dimethyl-l,3-propanediamine, and recrystallizing from chloroform/ethyl ether gives the title compound, mp 123.5 -124.5°, decomp. EXAMPLE 54 N,N’-DimethyI-N-(indolyl-2-carbonyl)-N’-(3-(l-methylethyl- 25 amino)-2-pyridinyl]-l,6-hexanediamine (III)

Follovving the general procedure of PREPARATIONS 34 and 35, and EXAMPLE 52, making non-critical variations but starting with N,N’-dimethyl-l,6-hexanediamine, and recrystallizing from chloroform/ethyl ether gives the title compound, mp 110 · 111°. EXAMPLE 55 2-(N-Methyl-N-(3-(l-methylethylamino)-2-pyridinylethyI indoI-2-30 carboxylate (III)

Palladium black (110 mg) is added to 2-(N-methyl-N-(3-nitro-2-pyridinyl)amino)* ethyl indol-2-carboxylate (PREPARATION 37, 195 mg) in methanol (75 ml). The mixture is stirred under a hydrogen atmosphere (balloon) for 30 min at 20-25°, filtered -74- and concentrated to give a solid. The solid is dissolved in ethanol (12 ml) and treated with acetone (0.64 ml) and sodium cyanoborohydride (27 mg). Acetic acid is added to adjust to pH 5 as measured on moistened pH tēst paper. The mixture is stirred for 3.8 days during which time additional sodium cyanoborohydride (39 mg) is added in 5 portions, adjusting the pH on each addition. The mixture is adjusted to pH 3 vvith aqueous hydrochloric acid (10%), neutralized with aqueous sodium hydroxide (5%) and concentrated under reduced pressure to 5 ml. The residue is diluted with chloroform, vvashed with water, saturated aqueous potassium carbonate, saline and dried over magnesium sulfate. Removal of solvent under reduced pressure gives an oil which is 10 chromatographed on silica gel (10 g, 230-400 mesh) eluting vvith a gradient of 10 * 50 % ethyl acetate/hexane. The appropriate fractions are pooled and concentrated to give the title compound, mp 130 - 131°. EXAMPLE 56 l-(Indolyl-2-carbonyl)-4-(3-cyc!opentylamino-2-pyridinyl)- • piperazine (III)

15 Follovving the general procedures of PREPARATIONS 6 and 7 and EXAMPLE 11 and making noncritica) variations but using cyclopentanone as the carbonyl component of the reductive amination reaction, the title'compound is obtained, mp 165.0 - 165.5°. EXAMPLE 57 l-(Indolyl-2-carbonyl)-4-(3-cyclopropylamino-2-pyrazinyl)piper- azine (III) 20 Cyclopropylamine (2.4 ml) is added to a solution of 2,3-dichloropyrazine (1.05 g) in dry tetrahydrofuran (5 ml). The mixture is stirred 20 hr at 20-25°, 24 hr at 50° and 24 hr at 65°. The mixture is diluted vvith ethyi acetate (50 ml), vvashed with saturated sodium bicarbonate solution (10 ml), dried vvith saline and over sodium sulfate and concentrated to an oil, a 10:1 mixture of 2-chloro-3-cyclopropylaminopyrazine and the 25 starting dichIoropyrazine. Piperazine (301 mg) is added to the oil (120 mg) and tetrahydrofuran (1 ml). The mixture is heaied 65 hr at 80°, diluted vvith ether (30 ml) and vvashed vvith vvater (10 ml) containing aqueous sodium hydroxide solution (5%, 2 ml). The aqueous phase is separated and extracted vvith ether (10 ml). The aqueous phase is saturated vvith sodium chloride and extracted vvith ether (3 x 10 ml). The ether 30 extracts are dried over sodium sulfate, concentrated and reconcentrated from chloroform to give l-(3-chloropyrazin-2-yl)piperazine. A solution of indol-2-carboxylic acid (18 mg) and l,r-carbonyIdiimidazole (19 mg) in dry tetrahydrofuran (1 ml) is stirred for one hour at 20-25° and a solution of the above piperazine (25 mg) in tetrahydrofuran (1 ml) -75- LV 10264 is added. After 2 hr, the mixture is diluted with methylene chloride (30 ml), vvashed with vvater and dried with saline and sodium sulfate. Removal of solvent gives a solid which is chromatographed on a 20 ml bed of silica gel packed with methylene chloride and eluted vvith 50 ml of 1%, 100 ml of 2% and 100 ml of 3% methanol/methylene 5 chloride. the appropriate fractions are pooled and concentrated to give the title compound, which solidifies on trituration with ether, mp 164-167°, decomp. EXAMPLE 58 2-(2-(N-Methyl-N-(indolyl-2-carbonyl)amino)ethoxy)-3-(l-methyl-ethylamino)pyridine (III)

Acetone (0.3 ml) and sodium cyanoborohydride (35 mg) are added to a solution 10 of 2-(2-N-methyl-N-(indolyl-2-carbonyl)amino)ethoxy)-3-aminopyridine (PREPARATION 39) in ethanol (10 ml) containing dimethylformamide. Acetic acid is added to adjust the pH to 4 as measured by placing an aliquot on moistened pH indicator paper. Additional sodium cyanoborohydride (20 and 25 mg) and acetic acid are added at intervāls. After stirring 3 days at 20-25° the pH is adjusted to 2, the solution is neutralized with aqueous 15 sodium hydroxide and concentrated under reduced pressure. The residue is taken up with chloroform and extracted vvith vvater, saturated potassium carbonate and vvater. The organic phase is dried vvith saline and magnesium sulfate and concentrated under redučed pressure. The material is chromatographed on silica gel vvith 1 % methanol/chloroform, . pooling appropriate fractions and then purified by preparative layer chromatography on 20 silica gel vvith ethyl acetate/hexane (1/1) collecting the band vvith Rf = 0.25-0.38 to give the title compound, NMR (CDC13) 10.06, 7.65, 7.44, 7.25, 7.11, 6.87, 6.77, 6.67, 4.67, 4.0, 3.48, 3.26, 1.05 δ. EXAMPLE 59 2-(2-(Indolyl-2-carboxy)ethoxy)-3-(l-methylethylamino)pyridine (III) 25 Follovving the general procedure of EXAMPLE 52 and making non-critical variations but starting vvith 2-(2-(indolyl-2-carboxy)ethoxy)-3-nitropyridine(PREPARA-ΉΟΝ 49) the title compound is obtained, mp 104-105.5° EXAMPLE 60 l-[5-(Ethoxycarbonylmethoxy)indolyl-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (III) 30 l-[5-Hydroxyindolyl-2-carbonyl]-4-[3-(l-methylethyIamino)-2-pyridinyI]piperazine (EXAMPLE 38, 95 mg) is added in one portion to a suspension of sodium iodide (6.75 mg) and anhydrous potassium carbonate (38 mg) in dry dimethylformamide (4.5 ml dried over molecular sieves). After stirring for 20 min ethyl bromoacetate is added dropvvise. -76-

The reaction mixture is then allowed to stir for about 72 hr at 20-25°. The reaction mixture is diluted with ethyl acetate, washed vvith saturated sodium bicarbonate, and saline, dried over magnesium sulfate, and concentrated to give an oil. The oil is purified on a silica gel flash column eluting with hexane/ethy] acetate (1/1), the appropriate fractions are pooled and concentrated to give an oil. This oil is crystallized from ether/hexane to give the tītie compound, mp 125.5-127.5°. EXAMPLE 61 l-[5-(CarbomethoxyindoIyl)-2-carbonyl]-4-[3-(l-methylethyl- amino)-2-pyridinyl]pipera2ine sodium salt (III) l-[5-(Ethoxycarbonylmethoxy)indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (III, EXAMPLE 60, 102 mg) is hydrolyzed with sodium hydroxide (2N, 0.11 ml) in ethanol (1 ml). After stirring at 20-25° for 1 hr, the reaction mixture is diluted with high purity water, frozen, and lyophilized to afford the title compound, mp 273-276°. EXAMPLE 62 l-(Benzimidazolyl-2-carbonyl)-4-[3-ethyl-2-pyridinyl]piperazine (III)

Benzimidazole-2-carboxylic acid (84 mg) and 1,1 ’-carbonyldiimidazole (84 mg) are dissolved in dry THF (1 ml) and stirred at- 20-25° for 130 min. The resulting solution is added via canula to a -10° cooled solution of l[3-(ethylamino)-2-pyridinyl]piperazine (International Publication No PCT/US86/0I797, PREPARATTON A-47, 122 mg) in dry THF (1 ml). The reaction mixture is then'allowed to reach 20-25° ovemight. The reaction mixture is then diluted with ethyl acetate, washed with saturated sodium bicarbonate, saline, and vvater, dried over magnesium sulfate, and concentrated to give an oil. The oil is purified on a silica gel flash column eluting with hexane/ethyl acetate, the appropriate fractions are pooled and concentrated to give a solid. The solid is recrystallized from hexane/methylene chloride the title compound, mp 161-163°. EXAMPLE 63 1 -(5-Fluoroindolyl-2-carbonyl)-4-[3-methylamino-2-pyridinyl]- piperazine (III) 5-Fluoroindole-2-carboxylic acid (98 mg) and l,r-carbonyldiimidazole (95 mg) are dissolved in dry THF (1 ml) and stirred for 2 hr at 20-25°. The resulting solution is added via canula to a -10° cooled solution of 4-[3-(methylamino)-2-pyridinyl]piperazine (117 mg) in dry THF (1 ml). The reaction mixture is then allovved to reach 20-25° ovemight. The reaction mixture is then diluted with ethyl acetate, washed vvith saturated sodium bicarbonate and saline, dried over magnesium sulfate, and concentrated to give -77- LV 10264 a solid, which is purified on a silica gel flash column eluting with hexane/ethyl acetate (1/1). The appropriate fractions are pooled and concentrated to give a solid. Recrystallization of the solid from ethyl acetate/ether gives the title compound, mp 194-195°. EXAMPLE 64 l-(5-Methoxyindolyl-2-carbonyl)-4-[3-(methylamino)-2-pyridinyl]piperazine (IV)

Following the general procedure of EXAMPLE 63 and making non-critical variations but starting with 5-methoxyindole-2-carboxylic acid, the title compound is obtained, mp 199-20Γ. EXAMPLE 65 l-(Indolyl-2-carbonyl)-4-[3-(methylamino)-2-pyridinyl]piperazine m

Following the general procedure of EXAMPLE 63 and making non-critical variations but starting vvith indole-2-carboxylic acid, the title compound is obtained, mp 153-154°. EXAMPLE 66 I-[Naphthyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinylJ- piperazine (III)

Following the general procedure of EXAMPLĒ 62 and making non-critical variations but starting vvith 2-napthoic acid the title compound is obtained, mp 146-148°. EXAMPLE 67 l-[5-(Benzyloxycarbonylmethoxy)indolyl-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (III) l-[5-Hydroxyindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridmyl]piperazine (EXAMPLE 38, 198 mg) is added to a heterogeneous solution containing anhydrous potassium carbonate (98 mg), sodium iodide (18 mg) and dimelhylformamide (1 ml). After stirring for 15 min benzyl bromoacetate (0.087 ml) is added dropvvise. The reaction mixture is allowed to stir for three days and then it is diluted vvith ethyl acetate, vvashed vvith saturated sodium bicarbonate and vvater, dried over magnesium sulfate, and concentrated to give an oil. The oil is purified through a silica gel flash column eluting vvith hexane/ethyl acetate (1/1), the appropriate fractions are pooled and concentrated to give a colorless oil. This oil solidifies on standing to give the title compound, mp 134-137°. EXAMPLE 68 l-[5-(Carboxymethoxy)indoIyl-2-carbonyl]-4-[3-(l-methylethyl-amino)-2-pyridinyl]piperazine (III)

Palladium on carbon (10%,. 44 mg) is added to a solution of l-[5* -78* (Benzyloxycarbonylmethoxy)indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2* pyridinyl]piperazine (EXAMPLE 67, 128 mg) in absolute ethanol (10 ml) and this mixture is subjected to 40 psi of hydrogen gas. After shaking for 2 hr, the reaction mixture is filtered and the solid material washed with absolute ethanol. The filtrate is 5 concentrated and filtered through Celite to give the title compound; NMR (CDC13/TMS) 1.22, 3.12, 3.52, 3.96, 4.62, 6.62, 6.78-7.05, 7.14, 7.69 and 10.28 δ. EXAMPLE 69 l-[Pyrrolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]-piperazine (III)

FoIIowing the general procedure of EXAMPLE 16A and making non-critical 10 variations but starting with pyrrole-2-carboxylic acid (0.30 g), l-(3-(l-methyīethyl-amino-2-pyridinyl)piperazine (PREPARATION 9, 0.59 g) and l-(ethyl)-3-(dimethyl-aminppropyI)carbodiimide (0.62 g), the title compound is obtained; NMR (300 MHz, CDClj) 7.68, 6.95-6.90, 6.83, 6.56, 6.25, 4.16, 3.98, 3.56, 3.12 and 1.25 δ. 1« EXAMPLE 70 ' l-[?yrrolyl-2-carbonyl]-4-(3-ethylamino-2-pyridinyl)piperazine (ΙΠ) 15 Following the general procedure of· EXAMPLE 16 and making non-critical variations but starting with pyrrole-2-carboxylic acid (0.50 g), l-(3-ethyI-2-pyridinyl)-piperazine (0.97 g), CDI (0.77 g) and THF (9 ml), the title compound is obtained, mp 61-62°; NMR (300 MHz, CDClj) 9.46, 7.70, 6.96-6.90, 6.84, 6.56, 6.25, 4.20, 3.98, 3.14 and 1.31 δ. 20 EXAMPLE 71 l-[6-Methoxy-7-methylindolyl-2-carbonyl]-4-(3-ethylamino-2- pyridinyl)piperazine (III)

Follovving the general procedure of EXAMPLE 16 and making non-critical variations but starting with 6-methoxy-7-methylindole-2-carboxylic acid (0.23 g), l-(3-ethyl-2-pyridinyl)piperazine (0.24 g)* l,r-carbonyldiimidazole (0.19 g) and THF 25 (3 ml), the title compound is obtained, mp’ 162-163°. EXAMPLE 72 l-(5,6-Dimethoxyindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (III)

FoIlowing the general procedure of PREPARATION 16A and making non-critical variations but starting with 5,6-dimethoxyindole-2-carboxylic acid (0.42 g), 1-(3-(1-30 methyIethylamino-2-pyridinyl)piperazine(0.42g)andl-(ethyl)-3-(dimethylaminopropyl)-carbodiimide (0.64 g), the title compound is obtained, mp 242-243?. EXAMPLE 73 l-[3-methylindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (III) -79- LV 10264

Following the general procedure of EXAMPLE 16A and making non-critical variations but starting vvith 3-methylindole-2-carboxylic acid .(PREPARATION 42, 0.58 g), l-(3-(l-methylethyIamino-2-pyridinyl)piperazine (0.73 g) and l-(ethyl)-3-(di-methylaminopropyl)carbodiimide (0.76 g), the title compound is obtained, mp 191-192°. 5 EXAMPLE 74 l-[Indolyl-2-carbonyl]-4-[2-(l-methylethylamino)-4-fluorophenyl]- piperazine (III) l-[Indolyl-2-carbonyl]-4-[2-amino-4-fluorophenyl]piperazine (PREPARATION 44, 0.74 g) is dissolved in meihanol (4.5 ml) and glacial acetic acid (3.13 ml) and acetone (0.24 ml) are added. After 10 min of stirring, sodium cyanoborohydride (0.21 g) is 10 added and the reaction is stirred 24 hr. Then mixture is poured into aqueous sodium hydroxide (10%, 75 ml) and extracted with chloroform (3 x 100 ml), dried over anhydrous sodium sulfate and filtered through a plug (20 g) of silica gel. The silica is washed with methanol/chloroform (5/95, 100 ml). The organic phases are combined and concentrated under reduced pressure to give the title compound, mp 154-155°. 15 EXAMPLE 75 l-[Indolyl-2-carbonyl]-4-[2-(l-methylethylamino)*5-fluorophenyl]- piperazine (III)

Follov/ing the general procedure of EXAMPLE 74 and making non-critical variations but starting with l-[indoIyl-2-carbonyI]-4-[2-amino-5-fiuorophenyI]piperazine (PREPARATION 46, 0.42 g), the title compound is obtained, mp 193-194°. 20 EXAMPLE 76 l-[ĪndolyI-2-carbonyl]-4-[3-(l-pyrrolidinyl)-2-pyridinyl]piperazine (III)

Following the general procedure of EXAMPLE 16A and making non-critical variations but starting with indo!e-2-carboxylic acid (0.12 g), l-[3-(l-pyrroIidinyl)-2-pyridinyl]piperazine (PREPARATION 48, 0.17 g) and l-(ethyl)-3-(dimethylamino-25 propyl)carbodiimide (0.17 g), the title compound is obtained, mp 181-182°. EXAMPLE 77 l-[3,5-Dimethyl-4-methoxybenzoyl]-4-[3-(ethylamino)-2*phenyl]- piperazine (IV)

FolIowing the general procedure of EXAMPLE 16A and making non-critical variations but starting with 3,5-dimethyl-4-methoxybenzoic acid (0.075 g), l-[3-30 -(ethylamino)-2-phenyl]piperazine (0.094 g) and l-(ethyl)-3-(dimethyIaminopropyl)carbo-diimide (0.10 g), the title compound is obtained, mp 75-77°. EXAMPLE 78 l-[3,5-Dimethyl-4-methoxybenzoyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (IV) -80-

Following the general procedure of EXAMPLE 16A and making non-critical variations but starting with 3,5-dimethyl-4-methoxybenzoic acid (0.075 g), l-[3-(l-methylethylamino)-2-pyridinyl]piperazine (0.101 g) and. l-(ethyl)-3-(dimethylamino-propyl)carbodiimide (0.096 g), the title compound is obtained, mp 89-93°. 5 EXAMPLE 80 l-[5-MethoxyindolyI-2-methyl]-4-[3-(ethylamino)-2-pyridinyl]- piperazine (TV) l-[5-Methoxyindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]-piperazine (0.20 g) is dissolved in toluene (0.5 ml) and cooled to -10°. Then diisobutyl-aluminum hydride (1M in toluene, 2.0 ml) is added dropvvise via syringe. The reaction 10 is slowly warmed to 20-25° and stirred for 18 hr. Then 2 more equivalents of diisobutylaluminum hydride are added and the reaction is warmed to 50°. After 3 hr, the reaction is cooled to 20-25° and quenched by the dropwise addition of 9.3 ml of methanol followed by water (0.75 ml). The mixture is stirred for 30 min and the precipitate is filtered off and the mother liquors are concentrated under reduced pressure. 15 The product is recrystallized from ethyl acetate to provide the title compound, mp 203-204°. EXAMPLE 81 l-(IndolyI-2-carbonyl]-4-(3-ethylamino-2-pyridinyl)-l,4-diazepine (ΠΙ) " ΐ

Following the general procedure of EXAMPLE 16 and making non-critical 20 variations but starting with l-(3-ethyIamino-2-pyridinyl)-l,4-diazepine(0.96 g), the title compound is obtained, mp 162-164°. EXAMPLE 82 l-(5-FluoroindoIyi-2-carbonyl)-4-(3-ethylamino-2-pyridinyi)-l,4- diazepine (ΙΠ)

Following the general procedure of EXAMPLE 16 and making non-critical 25 variations but starting with l-(3-ethylamino-2-pyridinyl)-l,4-diazepine(0.96 g), the title compound is obtained, mp 168-169°. EXAMPLE 83 l-(IndoIyl-2-carbonyl)-4-[3-(l-methylethylamino)-2-pyridinyl]-l,4- diazepine (ΙΠ)

Follovving the general procedure of EXAMPLE 16 and making non-critical 30 variations but starting with l-[l-methylethylamino)-2-pyridinyl]-l,4-diazepine (0.5 g), the title compound is obtained, mp 171-173°. EXAMPLE 84 l-(5-Fluoroindolyl-2-carbonyl)-4-(3-(l-methylethylamino-2-pyridin- yl)-l,4-diazepine (ΕΠ) -81- LV 10264

Following the general procedure of EXAMPLE y 16 and making non-critical variationsbut starting with l-(3-(l-methylethylamino-2-pyridinyl)-l,4-diazepine(0.50g), the title compound is obtained, mp 135-136°. EXAMPLE 85 l-[2-(5N-(N\N’-Dimethylaminomethylene)aminoindolyl)carbon-yl]-4-(3-(l-methylethylamino)-2-pyridinyl)piperazine, methane sulfonate (ΠΙ)

Dimethylformamide dimethyl acetal (0.067 g) and l-[2-(5-aminoindolyl)· carbonyl]-4-(3-(l-methylethylamino)-2-pyridinyl)piperazine(EXAMPLE 101,0.14 g) are dissolved in dimethylformamide (0.7 ml). The reaction is stirred at 20-25° for 3 hr, then diluted with methanol/chloroform (5/95), washed with water (3 x), saline, dried over anhydrous sodium sulfate and concentrated linder reduced pressure. Purification by flash column chromatography (30 g silica gel) eluting with methanol/chloroform (5/95), pooling and concentration of the appropriatcfractions gives a solid. Recrystallizadon of the solid from ethyl acetate/hexane gives the title compound, mp 139-142°.

The free base is dissolved in methanol and 1 eq. of methanesulfonic acid is added. Ether is added until cloudy and the vessel set aside until crystallization is complete. Filtration provided the mesyl salt of the title compound, mp 203-206°. EXAMPLE 86 I-[5-(2’-Aminoacetamido)indolyl-2-carbonyl]-4-(3-(l-methyl- ethylamino)-2-pyridinyl)piperazine hydrochloride (ΠΙ) l-[5-(2’-benzyloxyglycylamino)indolyl-2-carbonyl]-4-(3-(l-methyl-ethylamino)-2-pyridinyl)piperazine (PREPARATION 60, 2.58 g) is dissolved in ethanol/THF (2/1, 150 ml) and palladium'on carbon (10%, 0.3 g) is added. The reaction is hydrogenated at 40 psi for 10 hr, then filtered through a pad of celite and concentrated under reduced pressure to give theh free base of the title compound.

The amine is dissolved in methanol and cooled to 20-25°, then 1 eq. of trimethylsilyl chloride is added and ether is added until cloudy. The solids formed are recrystallized from methanol/ether to give the title compound, mp 189-191°. EXAMPLE 87 1 -[6-Methoxyindolyl-2-carbonyl]-4-[3-( 1 -methylethylamino)-2« pyridinyl]piperazine (ΠΙ)

Foliowing the general procedure of EXAMPLE 16 and making non-critical varaitions but starting with 6-methoxyindoIe-2-carboxylicacid (PREPARATTON63,0.35 g), l-[3-(l-methylethylamino)-2-pyridinyl]piperazine(0.40g), l,r-carbonyldiimidazole (0.31 g) and THF (6.6 ml), the title compound is obtained, mp 191-193°. -82- EXAMPLE 88 l-[4-Methoxyindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (ΠΙ)

Following the general procedure of EXAMPLE 16 and making non-critical varaitionsbut starting with 4-methoxyindole-2-carboxylicacid (PREPARATION 69,0.35 5 g), l-[3-(l-methylethylamino)-2-pyridinyl]piperazine(0.44 g), 1, r-carbonyldiimidazole (0.30 g) and THF (3.6 ml), the title compound is obtained, mp 196-197°. EXAMPLE 89 l-[5-Methylindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2* pyridinyl]piperazine (ΠΙ)

Following the general procedure of EXAMPLE 16 and making non-critical 10 varaitions but starting with 5-methylindole-2-carboxylic acid (0.23 g), l-[3-(ļ-methyl-ethylamino)-2-pyridinyl]piperazine (0.29 g) and l,r-carbonyldiimidazole (0.21 g) the title compound is obtained, mp 199-201°. EXAMPLE 90 l-[5,6-Methylenedioxyindolyl-2-carbonyl]-4-(3-(l-methylethyl- amino)-2-pyridinyl]piperazine (ΙΠ) 15 Follovving the general procedure of EXAMPLE 16A and making non-critical varaitions but starting with 5,6-methylenedioxyindole-2-carboxylicacid (PREPARATION 79, 0.30 g), l-[3-(l-methylethylamino)-2-pyridinyl]piperazine (0.32 g) and l-(ethyl)-3-(dimethylaminopropyl)carbodiimide (0.34 g), the title compound is.obtained, mp 220-22 Γ. 20 EXAMPLE 91 l-[5-Fluoro-6-methoxyindolyl-2-carbonyI]-4-[3-(l-methylethyl- amino)-2-pyridinyl]piperazine (ΙΠ)

Follovving the general procedure of EXAMPLE 16A and making non-critical varaitions but starting with 5-fluoro-6-methoxyindole-2-carboxylicacid (PREPARATION 92, 0.30 g), l-[3-(l-methylethylamino)-2-pyridinyl]piperazine (0.32 g) and 25 l-(ethyl)-3-(dimethylaminopropyl)carbodiimide (0.33 g), the title compound is obtained, mp 193-194°. EXAMPLE 92 l-(7-Bromo-6-methoxyindolyl-2-carbonyl]-4-[3-(l-methylethyl- amino)-2-pyridinyI]piperazine (ΙΠ)

Follovving the general procedure of EXAMPLE 16A and making non-critical 30 varaitions but starting with 7-bromo-6-methoxyindole-2-carboxylicacid (PREPARATION 83, 0.30 g), l-[3-(l-methylethylamino)-2-pyridinyl]piperazine (0.25 g) and l-(ethyl)-3-(dimethylaminopropyl)carbodiimide (0.326 g), the title compound is obtained, mp 179-180°. -83- LV 10264 EXAMPLE 93 H5-Bromoindolyl-2-caibonyl]-4-[3-(l-methylethylarnino)-2pyridin-yl]piperazine (ΠΙ)

Following the general procedure of EXAMPLE 16A and making non-critical varaitions but starting with 5-bromoindole-2-caiboxyIic acid (0.51 g), l-[3-(l-methyl-5 ethylamino)-2-pyridinyl]piperazine (0.47 g) and l-(ethyl)-3-(dimethylaminopropyl)carb-odiimide (0.49 g), the title compound is obtained, mp 229-230°. EXAMPLE 94 l-[5-Bromo-6-methoxyindolyl-2-carbonyl]-4-[3-(l-methylethyl- amino)-2-pyridinyl]piperazine (ΠΙ)

Following the general procedure of EXAMPLE 16A and making non-critical 10 variations but starting with 5-bromo-6-methoxyindole-2-carboxylic acid (PREPARATION 82, 0.40 g), l-[3-(l-methylethylamino)-2-pyridinyl]piperazine (0.33 g) and l-(ethyl)-3-(dimethylaminopropyl)carbodiimide (0.34 g), the title compound is obtained, mp 202-204°. EXAMPLE 95 T[6-(N,N-Dimethylamino)indolyl-2-carbonyl]-4-[3-(l-methyl- 15 ethylamino)-2-pyridinyl]piperazine (ΙΠ)

Following the general procedure of EXAMPLE 16A and making non-critical variations but starting with 6-(N,N-dimethylamino)indole-2-carboxylic acid (PREPARATION 89, 0.40 g), l-[3-(l-methylethylamino)-2-pyridinyl]pipera2ine (0.43 g) and l-(ethyl)-3-(dimethylaminopropyl)carbodiimide (0.45 g),the title compound is 20 obtained, mp 153-154°. EXAMPLE 97 l-(4-Methylindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (ΠΙ)

Following the general procedure of EXAMPLE 16A and making non-critical variations but starting with 4-methylindole-2-cart>oxylič acid (PREPARATION 86, 0.40 25 g), l-[3-(l-methylethylamino)-2-pyridinyl]piperazine (0.50 g) and l-(ethyl)-3-(di- methylaminopropyl)carbodiimide (0.52 g), the title compound is obtained, mp 165-167°. EXAMPLE 99 l-pndolyl-2-carbonyl]-4-[3-(l-ethylpropyl)amino)-2-pyridinyl]- piperazine (ΠΙ)

Follovving the general procedure of EXAMPLE 16A and making non-critical 30 variations but starting with indoIe-2-carboxylic acid (0.21 g), 1 -[3-( 1 -ethylpropyl)-amino)-2-pyridinyl]piperazine(PREPARATION73,0.30g), l-(ethyl)-3-(dimethylamino-propyl)carbodiimide (0.29 g) and THF (3 ml), the title compound is obtained, mp 165-166°. -84- EXAMPLE 100 l-[Indolyl-2-carbonyl]-4-[3-(l-ethylpropyi)amino)-2-pyridinylJ-piperazine (ΙΠ)

Following thc general procedūra of EXAMPLE 16A and making non-critical variations but starting with indole-2-carboxylic acid (0.095 g), l-[3-(l-ethyl-propyl)amino)-2-pyridinyl]piperazine (PREPARATION 73, 0.15 g), l-(ethyl)-3-(di-methylaminopropyl)carbodiimide (0.14 g) and THF (1.2 ml), the title compound is obtained, mp 190-192°. EXAMPLE101 l-[5-AminoindoIyl-2-carbonyI]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (III) l-[5-Nitroindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (EXAMPLE 103, 1.0 g) is dissolved in ethanol (60 ml) and THF (60 ml) and palladium on carbon (10%, 0.15 g) is added. The reaction is hydrogenated at 40 psi for 14 hr, then filtered through celite and concentrated under reduced pressure. Purification by flash chromatography, eluting with ethyl acetate/hexane (50/50 —► 75/25), pooling and concentrating the appropriate fractions gives the title compound, mp 212-214°. EXAMPLE 102 l-[5-Fluoromdolyl-2-caiixriyl]-4-[3-(2’,2'-<limethylpropylamino)-2- pyridinyl]piperazine (ΓΠ)

Following the general procedūra of PREPARATION 8 and making non-critical variations but starting vvith l-[5-fluoroindolyl-2-carbonyl]-4-[3-amino-2-pyridinyl]-piperazine (PREPARATION 78, 0.15 g), sodium cyanoborohydride (29.4 mg), trimethylacetaldehyde (38.1 mg), acetic acid and methanol (0.9 ml), the title compound is obtained, mp 205-206°. EXAMPLE 103 l-[5-Nitroindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridin- yl]piperazine (ΙΠ)

Following the general procedūra of EXAMPLE 16A and making non-critical variations but starting with 5-nitroindole-2-carboxylic acid (0.86 g), l-[3-(N-isopropyl)-amino)-2-pyridinyI]piperazine (0.43 g), l-(ethyl)-3-(dimethylaminopropyl)carbodiimide (0.45 g) and THF (4 ml), the title compound is obtained, mp 153-154°. EXAMPLE104 l-[5-Acetarnidoindoiyl;2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (ΠΙ) l-(5-Aminoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (EXAMPLE 101, 0.075 g) is dissolved in-methylene chloride (0.4 ml) and pyridine (0.016 g) is added and the reaction is cooled to 0°. Acetyl chloride (0.016 g) is added -85- LV 10264 and stirred for 2.5 hr. The reaction mixture is diluted with chloroform and vvashed with saturated aqueous sodium bicarbonate, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by fiash column chromatography, eluting with ethyl acetate, pooling and concentrating the appropriate fractions gives the 5 title compound, mp 136-138°. EXAMPLE 105 l-[5-Methanesulfonamidoindolyl-2-carbonyl]-4-[3-(l-methylethyI- amino)-2-pyridinyl]piperazine (ΠΙ) l-[(5-Aminoindolyl-2-cartx)nyl]-4-[3-(I-methylethylamino)-2-pyridinyl]piperazine (EXAMPLE 101, 0.075 g) is dissolved in methylene chloride (0.4 ml) and pyridine 10 (0.016 g) is added and the reaction is cooled to 0°. Then methanesulfonyl chloride (0.023 g) is added. After 2.5 hr of stirring, the reaction is diluted with chloroform and washed with saturated aqueous sodium bicarbonate, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate is dissolved in the minimum amount of chloroform and passed through a small plug of silica gel and then 15 it is recrystallized with ethyl acetate/hexane to provide the title compound, mp 226-228°. EXAMPLE 106 l-[5-Fluoroindolyl-2-carbonyl]-4-[3-(2-methoxy-l-methylethyl- amino)-2-pyridinyl]piperazine (ΙΠ)

Following the general procedure of PREPARATION 8 and making non-critical variations but starting with l-[5-fluoroindolyl-2-carbonyl]-4-[3-amino-2-pyridinyl]-20 piperazine (PREPARATION 129,0.15 g), methoxyacetone (0.04 g), sodium cyanoboro-hydride (0.029 g), acetic acid (0.53 g) and methanol (0.8 ml), the title compound is obtained, mp 163-164°. EXAMPLE 107 N,N’-Dimethyl-N-(5-methoxyindolyl-2-carbonyl)-N’-[3-(l-methyl- ethylamino)-2-pyridyl]ethylenediamine (TV) 25 Following the general procedure of EXAMPLE 52 making non-critical variations andemploying NlN’-dimethyl-N-(5-methoxyindolyl-2-carbonyl)-N’-(3-nitTo-2-pyridinyl) ethylenediamine (PREPARATION 74) the title compound is obtained, mp 116.5-117°. EXAMPLE 108 N,N’-Dimethyl-N-(5-fluoroindolyl-2-carbonyl)-N’-(3-(l-methyl- ethylamino)-2-pyridyl)ethylenediamine (ΙΠ) 30 Follovving the general procedure of EXAMPLE 52 making non-critical variations and employing N,N’-dimethyl-N-(5-fIuoroindolyl-2-carbonyI)-N’-(3-mtro-2-pyridinyl)-ethylenediamine (PREPARATION 75) the title compound is obtained, mp 121-122.5°. EXAMPLE 109 l-(7-AzaindolyI-2-carbonyl)-4-(3-(l-methylethylamino)-2- -86- pyridinyl)piperazine (III)

Following the general procedure of EXAMPLE 1 and making non-critical variations but starting with 7-azaindoIe-2-carboxylic acid (PREPARATION 76) and l-(3-(l-methylethylamino*2-pyridinyl)piperazine (II, PREPARATION 9) the title compound is obtained, mp 174-175®, EXAMPLE 110 l-(5-Azaindolyl-2-carbonyl)-4-(3-(l-methylethylamino)-2-pyridinyl)piperazine (ΙΠ)

Follovving the general procedure of EXAMPLE 1 and making non-critical variations but starting with 5-azaindole-2-carboxylic acid (PREPARATION 77) and l-(3-(l-methyIethylamino-2-pyridinyl)piperazine (Π, PREPARATION 9) the title compound is obtained. EXAMPLE 111 N,N’-Dimethyl-N-(indolyl-2-carbonyl)-N’-(3-(ethylamino-2- pyridinyI)-l,3-propanediamine (ΠΙ)

Following the general procedure of PREPARATIONS 34 and 35 and EXAMPLE 52 making noncritical varadons but starting with N,N’-dimethyl-l,3-propanediamineand employing acetaldehyde in the final reductive alkyl'ation step the title compound is obtained, mp 128.2-130.2°. EXAMPLE 112 N,N,-Dimethyl-N-(indoiyl-2-carbonyl)-N’-(3-(ethylamino-2- pyridyl)-l,6-hexanediamine (ΙΠ)

Following the general procedure of PREPARATIONS 34 and 35 and EXAMPLE 52 making noncritical varations but starting with N,N’-dimethyl-l,6-hexanediamineand employing acetaldehyde in the final reductive alkylation step the title compound is obtained, mp 146® decomp. EXAMPLE 113 l-[6-Formylindoyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (ΓΠ) (RAM-154) U-91440 Following the general procedure of EXAMPLE 16A and making non-oritical variations but starting with 6-formylindole-2-carboxylic acid (PREPARATION 98), and 1-(3-(l-methylethylamino)-2-pyridinyl)piperazine (PREPARATION 9), the title compound is obtained. EXAMPLE 114 l-[6-Nitroindoyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyri- dinyl]piperazine (ΙΠ)

Follovving the general procedure of EXAMPLE 16A and making non-critical variations but starting with 6-nitroindole-2-carboxylicacid (PREPARATION 95), the title -87- LV 10264 compound is obtained. EXAMPLE 115 l-[5-Azido-2-indolylcarbonyl]-4-[3-(l-methylethylamino)-2-pyri-dinyl]piperazine (ΙΠ) 1 -[5-aminch2-indolylcait>onyl]-4[3-(methyIethylamirio)-2-pyridinyl]piperazine (0.34 g) is dissolved in 30 ml of 80% acetic acid/water and cooled to -10°. Then sodium nitrite (0.0656 g) dissolved in 1.25 ml of water is precooled to 0° and then added dropwise to the aminoindole. After 30 min, sodium azide (0.062 g) dissolved in 1.25 ml of water is precooled to 0° and added dropwise. The reaction is stirred 2 hr at -10°. Then 30 ml of water is added and the product is extracted with ether (3 X 30 ml), saturated sodium carbonate (0°), water, saline, and then dried over anhydrous sodium sulfate. Purification by flash column chromatography (100 g silica gel, 25% ethyl acetate/chloroform) afforded 0.16 g of the product which is further purified by crystallization from ethyl acetate/tetrahydrofuran/hexane to provide the title compound, NMR (300 MHz, CD3OD) 7.39, 7.28, 7.16, 6.85-6.70, 6.66, 3.86, 3.48, 2.93, and 1.08 6. EXAMPLE 116 l-[4-Methoxy-3,4-dimethylbenzyl]-4-(3-(2-propenylamino)-2-pyridinyl]piperazine, hydrochloride (IV) A mixture of 3,5-dimethyl-4-methoxybenzyl chloride (0.13 g)l-[3-(2-propenyl-amino)-2-pyridinyl]piperazine (PREPARATION 118, 0.14 g), anhydrous potassium carbonate (0.18 g) and acetonitrile (6 ml) is refluxed under nitrogen for 18 hr. The mixture is cooled and then diluted with dichloromethane and aqueous saturated potassium carbonate solution. The phases are separated. The orgnaic phase is dried over anhydrous sodium sulfate and concentrated to an oil. The oil is flash chromatographed (1% methanol/chloroform) to provide 0.18 g of the title compound which is dissolved in ethereal hydrogen chloride to provide the hydrochloride salt, HRMS: calc. 366.2419 for CnH30N<O, found 366.2425. EXAMPLE 117 l-(Indolyl-2-carbonyl]-4-[3-(2-fluoroethylamino)-2-pyridinyl]- piperazine (ΠΙ)

Following the general procedure of EXAMPLE 16A and making non-critical variationsbut starting with l-[3-(2’-fluoroethylamino)-2-pyridinyl]piperazine(PREPARA-ΉΟΝ 106, 0.49 g), EDC (0.49 g), indoIe-2-carboxylic acid (0.32 g), the title compound is obtained, 180-181°. EXAMPLE 118 l-[Indolyl-2-carbonyl]-4-[3-(l-methylethyl)amino-2-pyrazinyl]- -88- 1,4-diazepine (III)

Following the general procedure of EXAMPLE 16A and making non-critical variations but starting with indole-2-carboxylic acid (0.19 g) and l-[3-(l-methyl-ethylamino)-2-pyrazinyl]-l,4-diazepine (PREPRATION 107), the title compound is obtained, m.p. 106-107°. EXAMPLE 119 l-[5-Benzyloxyindolyl-2-cart>onyl]-4-[4-(l,l-dimethylethylamino)- 2-pyridazinyl]piperazine (ΙΠ)

Following the general procedure of EXAMPLE 16A and making non-critical variations but starting with 5-benzyloxyindole-2-carboxylic acid, and l-[4-(l,l-dime-thylethylamino)-2-pyridazinyl]piperazine (ΡΚΕΡΑΙΙΑΉΟΝ 110), the title compound is obtained, dec. 132-133°. EXAMPLE 120 l-[5-Hydroxyindolyl-2-carbonyl]-4-[4-(l,l-dimethylethylamino)-2- pyridazinyl]piperazine (ΙΠ) l-[5-BenzyIoxyindoly!-2-carbonyl]-4-[4-(l, l-dimethylethylamino)-2-pyridazinyl]piperazine (EXAMPLE 119) is dissolved in 20 ml of methanol and 6 mg of 10% palladium on carbon is added followed by 0.25 g of ammonium formate. After stirring 2 hr at 20-25° the reaction is briefly heated with a heat gun to 40-50° and then allowed to stir at 20-25° a futher 1 hr. Then it is filtered through celite, the filter pad is washed with methanol, tetrahydrofuran and the organics are combined and concentrat-ed in vacuo to afford 1.33 g. The product is dissolved in 10% methanol/chloroform and washed with water, saline, dried over anhdrous sodium sulfate and concentrated in vacuo to afford the title compound, dec. 274°. EXAMPLE 121 l-[Benz[g]indolyl-2-carbonyI]-4-[3-(l-methylethylamino)-2- pyridinyljpiperazine (ΠΙ)

Following the general procedure of EXAMPLE 16A and making non-critical variations but starting with benz[g]indole-2-carboxylic acid (ΡΙΙΕΡΑΙΙΑΉΟΝ 112, 0.3 g) and l-(3-(l-methylethylamino)-2-pyridinyl]piperazine (ΡΙΙΕΡΑΙΙΑΉΟΝ 9, 0.34 g), the title compound is obtained, m.p, 190°. EXAMPLE 122 l-[Benz[e]indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (ΙΠ) «

Following the general procedure of EXAMPLE 16A and making non-critical variations but starting with benz[e]indole-2-carboxylic acid (ΡΙΙΕΡΑΙΙΑΉΟΝ 116, 0.5 g) and l-(3-(l-methyIethylamino)-2-pyridinyl]piperazine (ΡΙΙΕΡΑΚΑΉΟΝ 8, 0.52 g), -89- LV 10264 the dtle compound is obtained, m.p. 228-23Γ. HXAMPLE 123 N,N’-Dimethyl-N-(indolyl-2-carbonyl)-N’-(3-ethylamino-2-pyridyl)ethylenediamine (ΙΠ)

Following the general procedure ofPREPARATIONS 34 and 35 and EXAMPLE 52 making non-critical variations but employing acetaldehyde in the fmal reductive alkylation step the title compound is obtained, mp 140.(^140.5°. EXAMPLE 124 N,N’-Dimethyl-N-(indolyl-2-carbonyl)-N’-[3-(l-methylethyl- amino)-2-pyridyI]-l,4-butanediamine (ΠΙ)

Follovving the general procedure of PREPARATIONS 34 and 35 and EXAMPLE 52 and making non-critical variations but empioying N,N’-dimethyl-l,4-butanediamine, the dtle compound is obtained, mp 115.8-116.5°. EXAMPLE 125 l-[6-Hydroxymethylindolyl-2-carbonyl]-4-[3-(l-methylethyl- amino)-2-pyridinyl]piperazine (ΓΠ)

Following the general procedure of EXAMPLE 16A and making non-critical variations but starting with 6-hydroxymethylindole-2-carboxylic acid (PREPARATION 121), and l-[3-(l-methylethylamino)-2-pyridinyl]piperazine(PREPARATION9), the title compound is obtained. EXAMPLE 126 l-[6-Hydroxymethylindolyl-2-carbonyl]-4-[3-(ethylamino)-2- pyridinyl]piperazine (ΙΠ)

Following the general procedure of EXAMPLE 16A and making non-critical variations but starting with 6-hydroxymethytindole-2-carboxylic acid (PREPARATION 121), the title compound is obtained. EXAMPLE 127 l-[6-(N,N-Dimethylamino)methylindolyl-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (ΠΙ) l-[6-Methanesulfonylmethylindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (PREPARATION 122) is dissolved in acetonitrile and anhydrous potassium carbonate and dimethylamine were added. The reaction is heated to reflux and additional dimethylamine is added as necessary. After completion of the reaction, it is poured into anhydrous sodium bicarbonate and extracted with chloroform. The organic layers are dried over anhydrous sodium sulfate and concentrated in vacuo to provide the title compound. EXAMPLE 128 l-[Indolyl-7-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]- -90- piperazine (III)

Following the general procedure of EXAMPLE 16 and making non-critical variations but starting with indole-7-carboxylic acid, the title compound is formed (mp 154-155°). EXAMPLE 129 l-[Indolyl-7-carbonyl)-4-[3-(l-methylethylamino)-2-pyridinyl]- piperazine (III) 4-[3-(l-methylethylamino)-2-pyridinyl]piperazinē(PREPARATION9)isdissolved in dimethylformamideand 5,6-dihydro-pyrrolo-[3,2, l,i j]-[3, l]benzoxazine(PREPARA-TION 123) is added, The reaction is allowed to stir 6 hr. Then it is diluted with water and the solids are collected by filtration andrecrystallized from acetonitrile to provide the title compound, mp 171-172°. EXAMPLE 130 l-[Indolyl-7-carbonyl)-4-[3-(ethylamino)-2-pyridinyl]piperazine (m) 4-[3-(Ethylamino)-2-pyridinyl]piperazine is dissolved in dimethylformamide and 5,6-dihydro-pyrrolo-[3,2,l,iJj]-[3,l]benzoxazine-l,3-dione-quinoline-4,6-dione (PREPARATION 123) is added. The reaction is allovved to stir 2.5 hr. Then it is diluted with water and the solids are collected by filtration and recrystallized from acetonitrile to provide the title compound, mp 148-149°. EXAMPLE 131 l-(hdolyl-2-carbonyl)-4-(N-methyl-N-(3-(l-methylethylamino)-2-pyridinyl)amino)piperidine (ΠΙ)

Follovving the general procedure of EXAMPLE 52 and making non-critical variations but starting with l-(indolyl-2-carbonyl)-4-(N-methyl-N-(3-nitro-2-pyridinyl)· amino)piperidine (PREPARATION 127) the title compound is obtained, NMR (CDClj) 9.92,7.72,7.62,7.43,7.25,7.11,6.84, 6.77,4.68,4.50,3.56,3.48,3.14, .2.65,1.94, 1.67 and 1.22 $. EXAMPLE132 l-[6-Fluoroindolyl-2-carbonyl]-4-[3«(l-methylethyIamino)-2* pyridinylpiperazine (ΠΙ)

Following the general procedure of EXAMPLE 16 and making non-critical variations but using 6-fluoroindoIe-2-carboxylic acid (PREPARATION 66, 0.32 g) and l-[3-(l-methylethylamino)-2-pyridinyI]piperazine (0.40 g), the title compound is obtained, mp 177-178°. EXAMPLE133 l-[5,6-DimethoxyindolyI-2-carbonyl]-4-[3-ethyIamino-2- pyridinyl]piperazme (ΠΙ) -91* LV 10264

Follovving the general procedure of EXAMPLE 1$ and making non-cridcal variations but using 5,6-dimethoxyindole-2-carboxylie acid (0.50 g) and l-[3-ethylamino)-2-pyridinyI]piperazine (0.51 g), the title compound is obtained, HMRS = 409.2113 (theory for C^NA is 409.2114,

5 EXAMPLES 134-152 See CHART F

Following the general procedure of EXAMPLE 16 or 16A and making non-critical variations but using the [aryl/heteroaryl]-carboxylic acid of Column A and the pyridyl linker of Column B, the corresponding compounds of Column C are obtained. EXAMPLE 153 l-[2-(5-(N\N’-Dimethyfeminomethylene)aminoindolyl-2-carbonyl]-10 4-[3-(l, l-dimethylethylamino)-2-pyridinyI]piperazine (ΙΠ)

Following the general procedure of EXAMPLES 101 and 85 and making non-critical variations but using l-[5-nitroindolyi-2-carbonyl]-4-[3-(l,l-dimethylethylamino)-2-pyridinyl]piperazine (EXAMPLE 151, the title compound is obtained. EXAMPLE 154 l-[(6-Dimethylaminomethyl)indolyl-2-carbonyl]-4-[3-(l,l- 15 dimethylethylamino)-2-pyridinyl]piperazine (ΙΠ)

Following the general procedure of EXAMPLE 127 and PREPARATION122 and making non-critical variations but starting with l-[6-hydroxymethylindolyl)-2-carbonyl]* 4-[3-(l,l-dimethylethylamino)-2-pyridinyl]piperazine, the title compound is obtained.

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Column C N,N'-dimethyl-N-(indolyI-2-carbonyl)-N'-[(3-(l-methylethy1amino)-2-pyridinyl]-3-oxa-1,5-pentanediamine N,N',N'r-trimethyl-N-(indolyl-2-carbonyl)-N',-[(3-(1 -methylethylamino)-2-pyridinyl]diethylenetriamine 1 -(6-cyanoindolyl-2-carbon- yl)-4-[3-(ethyIamino)-2- pyridinyl]piperazine l-(6-pyridy!indolyl-2-carbon- yl)-4-(3-(l- methylethylamino)-2- pyridinyl]piperazine 1- (6-( l-pyrrolidinyl)indolyl- 2- carbonyl)-4-(3-( 1 -methylethylamino)-2-pyridinyl]piperazine Column B N,N'-dimethyl-N-[3-(l-methylethylamino)-2-pyridinyl]-3-oxa-l ,5-pentanediamine • V C .S ίλ E •r . ‘C S f .5 >; g E £ .Ξ « 4> * 5 =; 2 ϋ e* Γ* >*”= Z 5 >c 2 E & 1 <s ig !’B ’ 4.| . £ a v >, — c «Λ Έ ’T' >n — cx 1 -[3-( 1 -methylethylamino j-2-pyridinyl]piperazine __ 1 -[3-(methylethylamino)-2-pyridinyl]piperazine Column A Indolc-2-carboxylic acid Indole-2-carboxylic acid 6-Cyanoindole-2-carboxyIic acid 6-Cyanoindole-2-carboxylic acid 6-(l-Pyrrolidinyl)indole-2-carboxylic acid 0) * • c o o •es m c •«t ed £ w -102-

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CHARI-S lABLEi

The utility of this invention is demonstrated by the ability of the compounds used to inhibit virai reverse transcriptase, an enzyme essential for human immunodeficiency virus replication. This enzyme has characteristics which differentiate it from other known cellular polymerases and it is a unique enzyme which is not found in uninfected celis. EXAMPLE RT ΙΝΗΣΒΓΠ ON (100 μΜ) INHIBITION* OF SYNCYTIA FORMATION EDm 0*M) PBL3 ļ ΙΝΗΕΒΓΠΟΝ OFVIRAL REPLICATION (p24 & RNA) EDm (μΜ) . 1 60-79 10 1 3 70-76 1-2.5 1 1 4 58 2.5 SriO 1 5 39-42 2 NA 1 10 72-87 5 >1 1 11 95-98 0.3-3 0.01-0.1 1 12 64-80 <0.3 5-10 16 85-88 1.3 0.003 16A ΝΑ <0.2 • 0.001 17 96 £0.3 £0.01 19 65-71 3 0.1-1 20 64 10 1 21 44-74 1 0.01-1 22 76-82 <0.3-5 0.01 -105- LV 10264 EXAMPLE RT %x ΕΝΉΙΒΓΠ ON (100 μΜ) ΙΝΗΕΒΓΠΟΝ2 OF SYNCYTIA FORMATION ΕϋΛ (μΜ) PBL5 ΙΝΗΙΒΓΠΟΝ OF VIRAL REPLICATION (ρ24 & RNA) ΕϋΜ (μΜ) 23 92-95 <0.3 0.003-0.01 1 24 65-70 16 0.01-0.1 25 96 £0.3-0.4 0.003 ļ 26 97 £0.3-0.5 0.003 27 37-57 >0.001 10 28 70 >26 0.1-1 29 75-83 2.8 . 0.1-1 I 31 65-71 3 0.1-1 ļ 32 96 <0.3 0.003-0.01 34 41 . ΝΑ <10 35 57-70 ΝΑ ΝΑ 36 69-84 ΝΑ . 0.01 37 82-95 0.3 0.1 38 96-98 ΝΑ <0.001 42 63 2 10 44 89 0.1 0.001-0.01 45 83-91 0.5 0.01-0.1 46 89 1 0.001-0.01 47 91 ΝΑ 0.001-0.01 -106- 5 10 ļ EXAMPLE RT %' ΙΝΗΙΒΓΤΙ ON (100 |»M) INHEBITION* OF SYNCYTIA FORMA TION EDjņ (/xM) :TT'~'rn 1 |,,T,ļ PBL5 INHEBmON OF VIRAL REPLICATION (p24 & RNA) EDM 0»M) 1 48 63-92 NA 0.01-0.1 49 84-94 NA £0.1 1 50 84-97 NA 0,1 1 51 55 NA NA 52 89-94 NA 0.1-1 53 82-94 NA 0.001-0.01 1. 54 70-80 NA 0.1 | 55 66-79 NA o.i-i 56 79-93 NA 0.1-1 1 57 52-65 NA NA ļ 1 58 94-98 NA <0.1 ļ ļ 59 61-75 NA NA ļ 1 60 89-92 NA 0.1-1 61 91 NA 1 62 64-78 NA 1-10 63 82-88 NA 1 64 88-94 NA ' £1 65 81-93 NA £0.001 66 68-79 >280 1-10 15 -107- 5 10 LV 10264 EXAMPLE RT %' ΙΝΗΕΒΓΤΊ ON (100 μΜ) ΙΝΗΙΒΓΠΟΝ:. OF SYNCYTIA FORMATION EDm 0*M) ----"I'TI- ..... ...L. PBL3 ΕΝΉΕΒΓΓΙΟΝ OF VIRAL REPLICATION (p24 & RNA) EDm 0xM) 1 67 60-84 ‘ NA NA 68 78-95 NA NA 69 95 NA 0.1 70 83-91 2 ϊ>1 I 71 88-95 NA 0.01-0.1 72 43-66 NA <0.01 73 94-95 NA <0.001 74 82-84 NA 0.01-0.1 ļ 75 77 NA 0.01-0.1 76 65-76 NA 0.M 78 74 NA NA ļ 80 61-70 NA NA 8, 90-98 0.9 <0.001 82 87-93 10 0.01-0.1 83 97-98 <0.3 <0.001 84 97 NA <0.001 85 93-96 <0.2 0.001-0.01 86 78-96 <0.2 0.001-0.01 87 96-98 NA 0.01 15 -108- 5 10

EXAMPLE RT ΙΝΗΕΒΙΊΠ ΟΝ (100/χΜ) ΙΝΗΕΒΙΉΟΝ1 OF SYNCYT1A FORMATION ED„ (/xM) PBLJ ΙΝΗΕΒΓΠΟΝ OFVERAL REPLICATION (p24 & RNA) EDm (μΜ) 88 56-88 . NA 0.1 1 89 61-74 NA 0,1 90 96 NA <0.001 91 85-91 NA 0.1 92 94 NA 0.1-1 93 87 NA NA 94 85 NA 0.01-0.1 ļ 95 81-93 NA <0.001 I 97 52-80 NA £0.01 99 93-95 NA 0.001-0,01 ļ 100 81-82 NA NA ļ 101 93-96 NA 0.01 ļ 102 48 NA 10 103 72 NA <0.01 104 92-96 NA 0.01 105 82-96 NA £0.001 106 76-81 NA £0.001 107 77-87 NA NA 108 77-89 NA NA 15 -109- LV 10264 EXAMPLE RT %> ΙΝΗΕΒΓΠ ON (100 μΜ) INHIBITION* GF SYNCYTTA FORMATION EDjo (/iM) PBL3 ΙΝΗΕΒΓΠΟΝ OF VIRAL REPLICATION (p24 & RNA) EDm OzM) 109 56-82 NA NA ļ 111 86-92 NA ΝΑ ļ 112 74-82 NA NA ļ 113 92-96 NA NA ļ 116 45-52 NA CIO 117 92 NA NA ļ 119 53-58 NA NA ļ 120 87-90 NA NA ļ 121 64-70 NA NA 122 84 NA NA 123 47-60 NA NA 124 95 NA >0.1 . . 128 89-98 NA NA 129 68-84 NA NA 130 48-59 NA NA 131 85-97 NA NA 132 95-98 NA 0.001-0.01 133 76-84 1 0.01 -110- ΝΑ = not available. 1 Virai reverse transcriptase is found in extract$ from bacterial clones prepared according to the procedure described by Larder, B.f Purifoy D., Powell, K. and Darby, G., AIDS virus reverse transcriptase defined by high Ievel expression in 5 Escherichia coli., EMBO J. 6, 3133-3137 (1987). Inhibition of this enzyme is determined in a celi free assay which measures the Ievel of radioactive precursors incorporated into DNA. Extracts prepared according to the procedure of Kleid, D. G., et ai., Science, 1125-1129 (1981) are incubated in a mixture of inhibitor, 20 mM . dithiothreitol, 60 mM sodium chloride, 0.05% NP-40, 10 mM magnesium chloride, 10 50 mM Tris pH 8.3, 10 μΜ (“SJ-labeled deoxynucleoside-5’-triphosphate, 10 μg/ml RNA template (poly rC or poly rG) and 5 μg/ml DNA primer (oligo dG or oligo dT) for 15 minūtes at 37°. Incorporation of radio labeled precursor is determined by harvesting the trichloroacetic acid precipitated reaction mixtures on glass fiber filters, drying, and determining counts. The results of various assays are combined and 15 reported as % inhibition at a 100 μΜ dose in Table I. 1 The utility of this invention is further demonstrated by the ability of various compounds used to inhibit HlV-induced syncytia formadon in a tissue culture assay using MT-2 celis infected with HIV-1. This tēst is described by Nara et alM Quamitative infectivity assay for HIV-1 and -2, Nature 332, 469-470 (1988), as well 20 as in AIDS RESEARCH AND HUMAN RETROVIRUSES, vol. 4, No. 6, pages 449-455 (1988), Mary Ann Liebent, Inc., Publishers, and in an article by Mariano Busso, et al., entitled "Nucleotide Dimers Suppress HIV Expression Jn Vitro*. The results (EDjo means the concentration, in μΜ of drug, required to inhibit syncytia formadon to the extent of 50%) of various āssay are combined and reported in Table 25 I. In comparison, the known commercial compound, AZT, exhibited similar anti-HTV potency in this assay with 100 percent and 50 percent reducdons in syncytia formadon at concentrations of approximately 1 μΜ and 0.5 μΜ, respecdvely. 5 The utility of the compounds of the invendon is further demonstrated by the activity of this compound in the inhibition of HTV infection in primary peripheral 30 blood lymphocytes (primary PBL assay). The primary PBL assay offers the follovving advantages: (a) The assays are performed with primary human lymphocytes. Thereby, undesired testing of transformed celi lines is avoided in vvhich host celi and virus may -111- LV 10264 havc undergone proccsses of mutual adaptadon. Performance of celi culture in serum containing media closely mimics the in vivo situadon. (b) The primary PBL assay disdnguishes between true antiviral effect which is due to the drug and cytostat-ic/cytotoxic reacdons. (c) Virai replication is precisely followed by kinedc measure-ment of virai nucleic acids and proteins. (d) Nucleic acids (total HIV-RNA intra- and extracellular) and protein (secreted p24) are measured in parallel which permits one to differentiate between the compound’s effect on vīrus replication and on the expression of virai proteins. This leads to additional Information regarding the efficacy of the tēst compound. (e) Tolerance of the celi culture against low amounts of organic solvents also permits the investigation of hydrophobic substances, (f) The dose of the drug causing half maximal suppression of virus replication is determined. (g) The screening system is standardized and automated to a high degree.

The primary PBL assay uses the following procedūra:

Effects of the compounds of the invention on celi proliferation are determined by lymphocyte proliferation assays. Starting with a 100 micromolar solution, the compound is serially diluted 10 fold. One tenth of the concentration of a compound causing half maximal inhibidon of cellular proliferation is employed for ali subsequent testing.

Peripheral human lymphocytes are isolated by density gradient centrifugation. After stimulation by mitogen the celis are infected with a standardized preparation of HIV. Subsequently, the infected celis are ctiltured in the presence of the drug for four days. Individual cultures are established to measure virai replication three and four days follosving infection. Untreated celis and AZT-treated celis ara included as Controls in parallel with the drugs under investigation.

The amount of virai core protein p24 synthesized and released by the infected celis is determined in the supematant by the capture-ELISA technique on days three and four. By comparing with a Standard preparation, the amount of protein produced by the virus infected celis is quantified.

The total amount of virai RNA synthesized by the infected lymphocytes is determined by a special nucleic acid hybridization technique on days three and four of culture. By including a Standard preparation of HTV-RNA the amount of synthesized RNA is quantifīed.

If a drug shows antiviral effects in the. primary assay, ali steps of the primary -112- assay are repeated. In addition, viability of HlV-infected celis is determined in parallel wiih assays for virai p24 and RNA. In order to evaluate the half maximal antiviral effect of the drug, a concentration dependency of the drug action is measured. 5 Numerous examples of the compounds of the invention are assayed according to this procedure. The anti-HIV activity, as measured by the inhibition of the release of core p24 protein in HIV infected human lymphocytes, is used to calculate ED*,-antiviral (the concentration required to give a 50% reduction in p24 synthesis). The results are shown in Table I. 10 -113- LV 10264

CLAIMS 1. A diaromatic substituted compound of formula (III) *7 [Aryl/Ieceroaryl]-

(ΙΠ) where R, is -CH2-, -CO-, -CO*CH2-, -S02-, -CH=CH-CO-; where Z is

(Z-I) where (I) R2 is “O or R2.,:R2.2 where one of R2.j and R2.2 is -H and the other of R2.( and R2.2 is -H or -CH3, R3 is -0 or Rj.i:Rj.2 where one of *3-1 and RM is -H and the other of RM and Rw is -H or -CHj, R, is R*.j:R».2 and R5 is Rm:Rj.2 where one of Ru and R*.2 is -H and the other of Rn and R*.2 is -H or -CH3, \vhere one of RM and Rj.2 is -H and the other of Rj.j and Rj.2 is -H or -CH3, (Π) R« is R^j.'Rm and R3 is Rj.3:R^ where one of R«_j and Rm and one of Rj.3 and Ru are taken together to form -CH2- and the other of R^ and Rm, and Rj.3 and Rm arc -H, R2 and R3 are (TU) R2 is R2.3:R2^ and Rs is R^jiR^ where one of R2.5 and Rw and one of Rj. j and Rw are taken together to form -CH2-CH2- and the other of R2.5 and R2^, and Rj. j and Rw are -H, and R3 and R, are -114- (IV) Rj is Rj.j:Rj_4 and Rļ is R^jrRj^· where one of Rj.j and Rw and one of R^ i and R^ are taken together to form -CH2-CH2- and the other of Rj.j and Rw, and R*. j and Rm are -H, and R2 and Rj are -H:-H, (Z-II) -Yr(CH2)Bu-Z2-(CH3)a26-Y2- where na is 1 thru 5, n26 is 1 thru 5, Υ, is -0-, -S-, "N(Ym)- where Υ,., is C,-C4 alkyl, -ΟΟ'ν^Υ,.ϊ) where Y,.2 and Y,.3 are the same or different and are -H or C,-C4 alkyl, Y2 is -0-, -S-, -N(Y2.i)- where Y2.j is Ci-C4 alkyl, -C(Y2.3)(Y2.3) where Y2.2 and Y2.3 are the same or different and are -H or Ci*C4 alkyl, Z3 is nothing (a bond), -O-, -S-, -NfZ,.,)- where Z3., is -H or C,-C4 alkyl, -C-C-, •CiZ^fZ^)- where Zj.2 and Z3.3 are the same or different and are -H or Cj-C4 alkyl, cis and trans -C(Z^.2)=C(Z2.3)- where Z2.2 and are the same or different and are -H or CrC4 alkyl, with the provisos (1) that when Yt is -0-, -S- or -Ν(Υι.ι)-, then nu is 1 only when Z3 is nothing (a bond), -C*C-, -0(^.3)(2^.3)- or -0(^.3)=0(^.3)- and (2) that when Y2 is -O-, -S- or -N(Y2.,)-f then nM is 1 only when Zj is nothing (a bond), -C*C-, -0(2^)(2^.3)- or -0(2^.3)=0(2^.3)-, /—(CB2)a12

(z-m) where n,2 is 1 or 2 and n13 is 1 or 2, -115- LV 10264 (Z-IV) where nl2 and n13 are as defmed above, (Z-V)

WcH2)al23 where Y3 is -NOVi)- where Yj_, is Ct-C4 alkyl and n,2 and nl3 are as defined above; R* is -N=, -CH=, -N(0)-t R7 is -COO-R7.„ where R7.„ is as defmed above, -CO-N(R7.3)(Rw) where R7.3 and R7<4 are the same or different and are -H or Ci-C6 alkyl, *N(R7.5)(R7^) where R7.5 is C|-Q alkyl, -C(R7.u)(R7.I4)-(R7.n) where R7.13 and R7.16 are the same or different and are -H or Cj-C3 alkyl and where R7.,7 is C2-C5 alkenyl contaimng 1 or 2 double bonds or CfC5 alkynyl containing 1 triple bond, -CH2-CH2-OH, -ch2-ch2-ch2-oh, -CH(CH3)CH2-0-CH3, -CH(CH3)CH2-OH, -ch2-cf3, -CH2-cyclopropyl, -CH2-CH2F, -ch2-ch2-on, -C*R7.u-(CH2),m-C*H2 where R7.u is -H or -CH3> n,4 is 1 thru 5 and the carbon atoms marked with an asterisk (*) are bonded to each other to -116- resulting in the formadon of a ring, -(CHj)n,-N(R7.7)(R74) where n, is 2 or 3 and where R7.7 and R7.| are the same or different and are -H or C,-C4 alkyl, and where R7.7 and R74 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, 1-aziridinyl, and where R74 is -H, C,-Q alkyl, -C(R7.i5)(R7.l6)-(R7.t7) where R7.jj, R7.ie and R7.i7 are as defined above, -CH2-CH2-OH, -ch2-ch2-ch2-oh, . -CHjCFj, -CH2-CH2F, -ch2-ch2-c»n, or where R7.3 and R74 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl, N-morpholinyl or l-aziridinyl, (CH^-NCR^CRļ.Kj) where ^ is 1 or 2 and where R7.9 and R7.10 are the same or different and are -H or C,-C4 alkyl, and where R7.} and R7.10 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morphoIinyl, R, is -N=, -CRW= where Rw is -H, -F, -Cl, -Br, -CFj, -NOj, -COCFj, C|-Q alkyl, Cļ-Cj alkylthio, -OH, -0-Rm where Rw is Ci-C6 alkyl, -φ, -CO-R»., where Rw is C,- C6 alkyl or ·φ, -NH(Rm) where Rw is C.-C* alkyl, . -C(R|.7)(Rw)-(Rm) where R|.7 and Rw are the same or -117- LV 10264 \ different and are -H or C,-C, alkyl and where R»., is C2-C, alkenyl containing 1 or 2 double bonds or Cj-C} alkynyl containing 1 triple bond, -NR».j-CO-Rm where R^ is -H or 0,-0, alkyl and Rw is -H, C,-C4 alkyl or C,-C, alkoxy; R, is -N=, -CR*.,55 where R*., is -H, -F, -Cl, -Br, -NOj, -COCFj,

Cj-Ci alkyl,

Cj-Cj alkylthio, -OH, -O-Rm where R^2 is Cj-C6 alkyl, -Φ, -CO-R*j where R^j is C,- C6 alkyl or -ψ, -N(Rw)(R*.j) where R^ and R*s are the same or'different and are -H, Q-Q alkyl, -C(R»4)(R*.9)_(Rmo) where R94 and R9.9 are the same or different and are -H or Cj-Cļ alkyl and where R^o is C2-C5 alkenyl containing 1 or 2 double bonds or Cj-Cj alkynyl containing 1 triple bond, R*4 and R9.5 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, -NR94-CO-R9.7 where R94 is -H or 0,-0^ alkyl and R9.7 is -H, C,-Q alkyl or C,-C3 aIkoxy; R,0 is -N=, -CRio-i = where R10., is -H, -F, -Cl, -Br, -CF3, -NOj, -COCFj, C|-C* alkyl, C,-Cj alkylthio, -OH, -O-Rjo.2 where R,w is Ct-C6 alkyl, -φ, -CO-R1M where RIW is C,-Q alkyl or -φ, N(Rjcm)(Riw) where R1W and Rl0.j are the same or different -118- and are -H, C,-C4 alkyl, *C(Rio.ļ)(Rjo.9)*(Rio.ļū) where R,o.j and Rto.9 are the same or different and are -H or C,-C3 alkyl and where Rl0.i0 is C2-Cj alkenyl containing 1 5 or 2 double bonds or C2-C3 alkynyl containing 1 triple bond, -NR,m-CO-Ri0.7 where R1(W is -H or C,-C4 alkyl and Rl0.7 is -H, C,-C4 aikyl or C,-C3 alkoxy; with the proviso that not more than two of R«, R,, R, and R10 are -N=; Aryl/Heteroaryl is a substituent selected from the group of substituents of 10 formula (1) (1)

*2 15 where X, is -H, C,-C4 or n-alkyl, X2 is -H, Ο,-Cj or n-alkyl, X3 is C,-C4 alkyl, -CO-Xj., where ΧΜ is Ci-C4 alkyl or -φ, 20 -CHr*, -Φ; ... of formula (2)

(2) where X, and X5 are the same or different and are -H, C,-C4 alkyl, 30 -(CH^-NO^where n5 is 2 or 3 and where Χ4., and Χ^ are the same or different and are -H or C,-C4 alkyl or where X*, and Χ4.2 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, -119- LV 10264 and where X, and Xs are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrroIidinyl, 1-piperidinyl, l-piperazinyl or N-morpholinyl, and where X, and X2 are as defined above, with the proviso that both X« and Xj are not both -H; ... of formula (3)

E

where X< is -H, C,-Q alkyl, -F, -Cl, Br, -OH, -σθΗ2-φ, -O-CFj, -O-CHj-COC^,, where Χ^ is -H, C,-C6 alkyl,' -^ -CHj-φ, -CHO, C,-Cj alkoxy,

Cj-Cj alkylthio, -Ο-ΟΟ-Χ^ where X«.i is -H, C,-C4 alkyl or -Φ, -0-$Oj-X«.i2 where X$.j2 is Cj-C4 alkyl, -COO-X±u where is -H, Čļ-C4 alkyl, -φ or -CH2-φ, -C*N, "NOj, -Nj, -ΝΧίΙ,οΧί.,, where Χ^ι0 and X^n are the same or different and are -H or Cj-Cj alkyl or where X*.,,, and Χ*.,, are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, l-piperidinyl, l-piperazinyl, N-morpholinyl or l-aziridinyl, -N^CCH^-N^,)^) where n3 is 2 thru 5, X« is -H or CM alkyi, X*.3 is -H or CM alkyl, X^ is -H or CM alkyl, or where X*., and -120-

Xw are taken together wiih the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl, N-morpholinyl or l-aziridinyl, -O-CO^H^-COOH, where n3 is as defined above, -(MCH^-NpC^pC^·) where n3, X«.3 and X^ are as defrned above, •(CH^-OH, where is 1 thru 5, -(CH2)b6-N(X6.j)(Xw) where n« is 1 thru 5 and X*.5 and are the same or different and are -H, C,-C4 alkyl or where X*.3 and X^ are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrroIidinyI, l-piperidinyl, l-piperazinyl or N-morpholinyl, -NH-SOj-^ vvhere X*.7 is C,-C4 alkyl, C3-Cj cycloalkyl, «φ or ’K=C(X^)-N(X±7)(Xu) where (a) X*j is C,-C4 alkyl, Cj-C, cycloalkyl or -<f> and where X*_4 and X*_7 are as defined above, (b) X$_7 and Χ^ are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, (c) and X*.7 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl or l-piperidinyl, -ΝΧ^-ΟΟ-Χ*., where Χ^, is -H, CrC4 alkyl or ·φ and where X*4 is as defrned above, • * -O-prodrug where prodrug is -P02-O cation"·, -C0-CH2-C0-NH-CH2-S02-0· cation*, where n21 is 1-7 and R51 is -COO* cation+, -NRji.iRJt.2 where R3I.| and R3i.2 are the same or different and are -H or C,-Cj alkyl, -N+Ril.iRj1.2RJ,.jhalide*where R5M, R31.2 and R51.3 are the same or different and are -H or Cj-C3 alkyl, and where halide is -C1 or -Br, -CO-CH(amino acid)-NH2 where amino acid is -H, -121- LV 10264 -CHj, -CH(CH,)2, -CH2-CH(CH3)2, -CH2-OH, -CH(OH)(CH3), -CHj-Φ, -CH2-[p-hydroxyphenyl], -CH2-[3-indolyl], -CHj-S-S-CHj-CHCNHjJ-COOH, -CH2-SH, -CHjCHj-S-CHj, -CH2-CCX)H, -ch2-co-nh2, -ch2-ch2-cooh, -ch2-ch2-co-NH2, -CH2-[2-HISTIDYL], -(CH^j-NH-C^-NHj, -(CH^.-NHj, -ch2-ch2-CH(OH)-CH2-NH2, -(CH^j-NHj, -(CH^j-NH-CO-NH, -ch2ch2-oh, -CO-CH=CH-CO-O' cation+, -CO-N*-CH=CH-N=CH* where the atoms marked with an asterisk 0 are bonded to each other resulting in the formation of a ring, -CO-C**C[(CH2)^-NH2]-CH=CH-CH=CH* where is 1 or 2 and where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring, -CO-C’=CH-CH=C(-NRJ2)-CH=CH· where RJ2 is -H or Cj-Cj alkyl and where the atoms marked with an asterisk 0 are bonded to each other resulting in the formation of a ring, -CO-tCH^-CO-O-fCjHuOj sugars], -C0-0-CH(CH2-0-C0-RJ3)2 where the RJ3’s are the same or different and are Cj-C,», -CO-CCHjJ^CO-NCCHjJ-CHj-CHj-SO,’ cation+, -CH2*0_C0-(CH2)B2j-NRjļ.jRjļ.2 where n2j, Rjj.j and Rjj.j are as defined above, -CO-NH-OH^Rjj where R33 is -H or C3-Cj alkyl, -N02, -NRjj.jRj!.; where Rjm and RS1.2 are as defined above, -ΝΧ^-prodrug where and prodrug are as defined above except that prodrug is not -P02-0·, nj is 1 thru 3, the X«’s can be the same or can be different and where when n2 is 2 and the two X< groups are ortho to each other they can be taken together to form -0-CH2-0-; with the proviso that if n2 is 2 or 3, only one of the JC^s can be a prodrug, ... of formula (4)

1 (4) -122- where Q, is -NX,,.where X„ is -H, -S02-Φ, -S02-CHj, -CO-Χ,,., where X,,., is C,-C4 alkyl, -CF3 or -φ; Q2 is -N= provided R, is not -CH2-, -CX12= where XI2 is 5 -COO-X12.j where Xl2.t is -H or C,-C4 alkyl, -CO-N(Xi2.2)(Xi2.j) where Xļ2.2 and X,2.3 are the same or different and are -H, C(-C4 alkyl or where X,2.2 and X,2.2 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, 10 -CO-COO-Xu.i where X|2., is as defmed above, Cļ-Cj alkyl, -CO-φ, -CO-X,2., where X,2.| is as defined above, -CO-CO-N(Xi2.2)(X|2.j) where X,2.2 and X,2.2 are as defined 15 above, -(CH^-OH where na is 1 or 2, and where X< and n2 are as defined above, ... of formula (6) 20 ίί’ΊΓΊΙ (6) ... of formula (7) 25 x14

(7) where JJLti is a single or double bond, XI4 is -H, -O-CHj-φ, -O-CFj, 30 -123- LV 10264 •0-CH2-CCX)R|4.ļo where Rl4.,0 is -H, C,-C4 aikyl, ·φ or C,-Q alkyl, -F, -Cl, Br, -0-SQrXu.ii where X14.u is C,-C4 alkyl,' 5 -ON, -CHO, •(CHj^-OH where nu is 1 thru 5, -NO,, -NH2, -N3i -NH-CHj-ψ, -NH-SOj-Χμ.! where Xl4.', is CrC6 alkyl, Cj-C, cycloalkyl 10 or -Φ, -ΝΧ,^ΟΗ^-ΝΐΧμ,ΛίΧ,Μ) where n3 is 2 thru 5, Xl4.2 is -H or CM alkyl, Xl4.3 is -H or Cw alkyl, X1M is -H or CH alkyl, or where X14.3 and X144 are taken together with the attached nitrogen atom to form a heterocyclic ring selected fforn the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-15 morpholinyl, -NXi4.|jX|4.|4 where Xt4.,3 and Xl4.M are the same or different and are -H or C,-C5 alkyl or where Xl4.,3 and Xl4_,4 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, 20 where is 1 thru 5 and Χ^ and Xi44 are the same or different and are -H, C,-C4 alkyl or where Xl4.3 and X144 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, -N=C(Xi4-i)-N(Xi4.1)PC144) where 25 (a) Xw and Xl44 are Cļ-C6 alkyl, CyC, cycloalkyl or -φ, where

Xj4_4 is as defined above, (b) X14.7 and X,M are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, 30 (c) and Xl4.7 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1 -pyrrolldinyl or l-piperidinyl, -C0-0-Xl4_7 where Xl4.7 is as defined above, -124- 'CO-NPC,^)^^,) where X14_7 and Xl4., are as defmed above, -Νρζ^^-ΟΟ-Χ^, where Xl4.9 is -H, C,-C4 alkyl or -φ where X14.2 is defined above, -N(Xl4.j)-prodrugf where prodrug is as defined above except that it is not -POj-O", and when Xl4.2 is as defined above, n, is 0 thru 2, X* and Qj are as defined above; ... of formula (8) *22

where X2I is -H, Cj-C4 alkyl, -CO-(C|*C4 alkyl), -CH,-φ, -CO-<ļ> or -prodrug where prodrug is as defined above,

Xz2, Χ23 and Χχ are the same or different and are *F, -Cl, Br, -OH, -aCH2-φ, -O-CFj, -0-CH2-C00H, C,-Cj alkoxy, C,-Cj alkylthio, -0-C0-Xa., where X2., is -H, C,-C4 alkyl or -φ, -NO,, -NH„ -Nj, -ON, 'ΝΧ,,.,ίΟΗ^,,-ΝίΧπ.,)^^) where n, is 2 thru 5, XB.2 is -H or C,-C4 alkyl, Χ^ is -H or Q-C4 alkyl, Xa4 is -H or C,-C4 alkyl, and where Xa.j and Xa4 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, -0-00-(011,).9-00011, where n, is as defined above, -Ο-ίΟΗ^^-ΝίΧπ^ίΧ^) where n*, Xa., and XB4 are as defined above, -125- LV 10264 -(CH^m-N^a.jJOCa^) where nl0 is 1 thru 5 and and are the same or differcnt and are -H, Cj-C4 alkyl and where Xn.j and Xn4 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or Ņ-morphoIinyl, •N(Xa.7)(X23.i) where Xn.7 and ΧΏ4 are CrC6 alkyl, C3-C7 cycloalkyl or -φ, and where any adjacent two of -0-X2„ Xn, ΧΜ or XM are taken together to form a methylenedioxy group (-O-CHj-O-), Oļ and .... are as defined above; ... of formula (9)

(9) where X,0 is -H, -F, -C1 or -Br,

Qj is -CH- or Q2 where (¾ is as defined above, X* and Xu are as defined above; ... of formula (10) where X«, Xu ... of formula

(10)

OD

(11) -126- where X7 is -H, -SO2-φ, -SOj-CH,, -CO-X7., where X7., is C,-C4 allcyl or ·φ, 5 X, is -H, C,-C6 alkyl, -CH2-<*>, -SO2-<t>, -S02-CH3, -CO-XM where Xw is C,- C4 alkyl or ^ is as defined above; 10 ... of formula (15)

where (¾ and X„ are as defīned above; ... of formula (16) 20

*11 (16) 25 where Qj and Xu are as defīned above; ... of formula (17)

where (¾ and X„ are as defined above; -127- LV 10264 ... of formula (18)

(18) where Qj and XM are as defined above; ... of formula (19)

(19) where Qj and Xu are as defined above; ... of formula (20)

(20) where Qj and Xu are as defined above; ... of formula (21)

w.7-£ where Q„ X4 and % are as defined above; with the proviso that one of R7.5 or R^ must be -H when R* is not -N=, enantiomers, pharmaceutically acceptable salts, hydrates and solvates thereof. (21) -128- 2. A diaromatic substituted compound (III) according to claim 1 vvhere R, is -CO-. 3. A diaromatic substituted compound (III) according to claim 1 vvhere Z is (Z-II) 5 where Y, is -N(Y,.,)-, Zj is -CCZ^Zj.j)- where Zj.j and Zj.j are -H, and Y2 is -N(Ym)- or -0-. 4. A diaromatic substituted compound (III) according to claim 1 vvhere Z is (Z-III) 10 /"(CH2)ai2 — N )_ ^—(CH2>fl13 vvhere n12 is 1 and nl3 is 1 or 2. 15 5. A diaromatic substituted compound (III) according to claim 1 vvhere R« is -N=. 6. A diaromatic substituted compound (III) according to claim 1 vvhere and R, are -N*. 20 7. A diaromatic substituted compound (III) according to claim 1 vvhere R,, R, and R,0 are -CH= and R< is -N=. 8. A diaromatic substituted compound (III) according to claim 1 vvhere R7 is -N(R7.j)(R7J vvhere one of R7.5 and R^ is -H and the other of R7.j and Rw is C|-C« 25 alkyl. 9. A diaromatic substituted compound (III) according to claim 8 vvhere C,-C4 alkyl is -CH2-CH„ -CH(CHj)2 or -C(CH3),. 30 10. A diaromatic substituted compound (ΠΙ) according to claim 1 vvhere Aryl/«

Heteroaryl is selected from the groups of compounds of formulas (4), (7), (8), (9), (10), (11), (15) and (21). -129- LV 10264 11. A diaromatic substituted compound (III) according to claim 1 where Aryl/-Heteroaryl is selected from the groups of compounds of formulas (4), (7) and (8). 12. A diaromatic substituted compound (III) according to claim 1 which is l-[indolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyi]piperazine, 1 -[indolyl-2-carbonyl]-4-[3-( 1 -methylethylamino)-2-pyridinyI]piperazine, l-[indolyl-2-carbonyl]-4-[3-(N,N-diethyIamino)-2-pyridinyl]piperazine, l-[indolyl*2-methyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, l-[5-fluoroindolyl-2-carbonyl]-4-(3-(propylamino)-2-pyridinyl]piperazine, l-[5-chloroindolyl-2*carbonyl]-4-[3-(ethylamino)-2-pyridinyl]pipra2ine, l-[5-fluoroindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, l-[5-ethylindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, l-[5-fluoroindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]-piperazine, l-[benzofuroyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, l-[indolyl-2-carbonyl]-4-[2-(ethylamino)phenyl]piperazine, l-[indolyl-2-carbonyl]-4-[3-(cyclopropylmethylamino)-2-pyridinyl]piperazine, l-[5-fluoroindolyl-2-methyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine, l-[indolyl-2-carbonyl]-4-[3-(2,2,2-trifluoroethylamino)-2-pyridinyl]piperazine> l-[5-fluoroindolyl-2-carbonyl]-4-[3-(2>2,2-trifluoroethylamino)-2-pyridinyl]· piperazine, l-(5-benzyloxyindolyl-2-carbonyl]-4-(3-ethylamino-2-pyridinyI)piperazine, l-[5-benzyloxyindolyl-2-carbonyl]-4-[3-(l-methylethyl)amino-2-pyridinyl]- piperazine, l-[indolyl-2-methyI]-4-[3-(l-methyIethylamino)-2-pyridinyl]piperazine, l-[indolyl-2-carbonyl]-4-(3-(l,l-dimethylethylamino)-2-pyridinyl]piperazine, l-[5-fluoroindolyl-2-carbonyl]-4-[3-(i,l-dimethylethylamino)-2-pyridinyl]- piperazine, l-(5-fluoroindolyl-2-carbonyl)-4-(3-(l-methyIethyIamino)-2-pyrazinyI]- piperazine, l-(5-fluoroindolyl-2-carbonyl)-4-[5-(l-methylethylamino)-4-pyrimidinyl]- piperazine, 1 -(indolyl-2-carbony l)-4-[4-( 1 -methylethylamino)-3 -pyridazinyl]piperazine, -130- l-(5-fluoroindolyl-2-carbonyl)-4-[4-(l-methylethyl)amino)-3-pyridazinyl]- piperazine, 1- [5-fluoroindolyl-2-carbonyl]-4-[3-(l,l-dimethylamino)-2-pyrazinyl]-piperazine, N,N,-dimelhyl-N-(indolyl-2-carbonyI):N’-(3-(l-methylethylamino)pyrid*2-yl)- ethylenediamine, N,N’-dimethyl-N-(indolyI-2-carbonyl)-N,-[3-(l-methylelhylamino)-2-pyridyI]- 1,3-propanediamine, N,N’-dimethyl-N-(indolyI-2-carbonyl)-N’-[3-(l-methylethylamino)-2-pyridinyl]-1,6-hexanediamine, I. 2- (N-methyl-N-(3-(l-methyIethylamino)-2-pyridinylethylindol-2-carboxyIate, l-(indolyl-2-carbonyl)-4-[3-cyclopentylamino-2-pyridinyl]piperazine, 1- (indolyl-2-carbonyl)-4-(3-cyclopropylamino-2-pyrazinyl)piperazine, 2- (2-(N-methyl-N-(indolyl-2-carbonyl)amino)ethoxy)-3-(l-methylethylamino)-pyridine, 2-(2-(indolyl-2-carboxy)ethoxy)-3-( 1 -methylethylamino)pyridine, l-[5-(ethoxycarbonylmethoxy)indolyl-2-carbonyI]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine, l-[5-(carbomethoxyindolyl)-2-carbonyl)-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-(benzimidazolyl-2-carbonyl)-4-[3-elhyl-2-pyridinyI]piperazine, l-(5-fiuoroindolyl-2-carbonyl)-4-[3-methylamino-2-pyridinyl]piperazine, l-(indolyl-2-carbonyl)-4-[3-(methylamino)-2-pyridinyl]piperazine, l-[naphthyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, 1 -[5-(benzyloxycarbonyl methoxy)indoIyl-2-carbonyl]-4-[3-( 1 -methylethyl-amino)-2-pyridinyl]piperazine, l-[5-(carboxymethoxy)indolyl-2-carbonyI]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[pyrrolyl-2-carbonyI]-4-[3-(l-methylethylaxnino)-2-pyridinyl]piperazine, l-[pyrrolyl-2-carbonyl]-4-(3-ethyIamino-2-pyridinyl)piperazine, ✓ l-[6-methoxy-7-methylindolyl-2-carbonyl]-4-(3-ethylamino-2-pyridinyI)- piperazinc, l-[5,6-dimethoxyindolyl-2-carbonyl]-4-(3-(l-methylethylamino)-2-pyridinyl)- -131- LV 10264 piperazine, l-[3*methylindolyl-2-carbonyl]-4-(3-[l-methylethylajnino)-2-pyridinyl]- piperazine, l-[indolyl-2-caitonylj-4-[2-(l-methylethylamino)-4-fluorophenyl]piperazine, 5 l-[indoIyI-2-carbonyl]-4-[2-(l-methyIethylamino)-5-fIuorophenyI]piperazine, l-[indolyl-2-carbonyl]-4-[3-(l-pyrrolidinyI)-2-pyridinyI]piperazine, l-[indolyl-2-carbonyl]-4-(3-cthylamino-2-pyridinyl)-l,4-diazepine, l-(5-fluoroindolyl-2-carbonyl)-4-(3-ethylamino-2-pyridinyi)-l,4-diazepine, l-(indolyl-2-carbonyl)-4-[3-(l-methylethylamino)-2-pyridinyl]-l,4-diazepine, 10 l-[2-(5N-(N\N,-dimethylaminomethylene)aminoindolyl)carbonyl]-4-(3-(l- methylethylamino)-2-pyridinyl)piperazine, l-[5-(2’-aminoacetamido)indolyl-2-carbonyl]-4-(3-(l-methylethylamino)-2- pyridinyl)piperazine, 1 -[6-methoxyindolyl-2-carbonyl]-4-[3-( 1 -melhylethylamino)-2-pyridinyl]-15 piperazine, l-[4-methoxyindolyl-2-carbonyl]-4-[3-(l-rnethylethylamino)-2-pyridinyl]- piperazine, l-[5-methyIindolyI-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]- piperazine, 20 l-[5,6-methylenedioxyindolyl-2-carbonyl]-4-[3-(l-methyIethylamino)-2-pyridin- yl]piperazine, l-[5-fluoro-6-methoxyindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[7-bromo-6-methoxyindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-25 pyridinyl]piperazine, l-[5-bromoindolyi-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]- piperazine, l-[5-bromo-6-methoxyindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazinc, 30 l-[6-(N,N-dimethylamino)indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazinc, l-[4-methylindolyl-2-carbonyl]-4-[3-(l-melhylethylamlno)-2-pyridinyl]- piperazine, -132- 1 -[indolyl-2-carbonyl]-4-[3-( 1 -ethylpropyl)amino-2-pyridinyl3piperazine, 1 -[indolyl-2-carbonyl]-4-[3-( 1 -ethylpropyl)aminq)-2-pyridinyl]piperazine, l-[5-aminoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]-piperazine, l-[5-fluoroindoIyl-2-carbonyl]-4-[3-(2’,2,-dimethylpropylainino)-2-pyridinyI]- piperazine, l-[5-nitroindolyl-2-carbonyl]'4-[3-(l-methylethylamino)-2-pyridinyl]piperazme, l-[5-acetamidoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]- piperazine, l-[5-methanesulfonamidoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-fluoroindolyl-2-carbonyl]-4-[3-(2-methoxy-l-methylethylamino)-2-pyridiny l]piperazine,. N,N’-dimethyl-N-(5-fluoroindolyl-2-carbonyl)-Nt-(3-(l-methylethylamino)-2- pyridyl)ethylenediamine, 1 -(7-azaindolyl-2-carbonyl)-4-(3-( 1 -methylethylamino)-2-pyridinyl)piperazine, 1 -(5-azaindolyl-2-carbonyl)-4-(3-( l-methylethylamino)-2-pyridinyl)piperazine, N,N’-dimethyl-N-(indoIyl-2-carbonyI)-N,-(3-(ethylamino-2-pyridinyl)-l,3· propanediamine, N,N,-dimelhyI-N-(indolyl-2-carbonyl)-N’-(3-(eihylamino-2-pyridyl)-l,6- hexanediamine, 1 -[6-formylindoyl-2-carbonyl]-4-[3-( 1 -methylethylamino)-2-pyridinyl]-piperazine, l-[6-nitroindoyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine, l-[5-azido-2-indolylcarbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]- piperazine, l-[indolyl-2-carbonyl]-4-[3-(2-fluoroethylamino)-2-pyridinyl]piperazine, l-[indoIyl-2-carbonyl]-4-[3-(l-methylethyI)amino-2-pyrazinyl]-l,4-diazepine, l-[5-benzyloxyindolyl-2-carbonyl]-4-[4-(l, 1 -dimethylethylamino)-2-pyridazinyl]piperazine, 1-[5-hydroxyindolyl-2-carbonyl]-4-[4-(l, 1-dimethylethylamino)-2-pyridazinyl]-piperazine, l-[beru[g]indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]« -133- LV 10264 piperazine, l-[benz[e]indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]- piperazine, N,N’-dimelhyl-N-(indolyl-2-carbonyl)-N’-(3-ethylamino-2-pyridyl)ethylene- diamine, N,N’-dimethyl-N-(indolyl-2-carbonyl)-N’-[3-(l-methylethylamino)-2-pyridyl]- 1,4-butanediamine, l-[6-hydroxymethylindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]- piperazine, l-[6-hydroxymethylindolyl-2-carbonyl]-4-[3-(elhylamino)-2-pyridinyI]- piperazine, l-[6-(N,N-dimethylamino)methylindoIyI-2-carbonyl]-4-[3-(l-methylethyIamino)-2- pyridinyl]piperazine, l-[indolyl-7-carbonyl]-4-[3-(l-methylethylamino)-2-pyridmyl]piperazine, l-[indolyl-7-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine, l-[indolyl-7-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine,· l-(indolyl-2-carbonyl)-4-(N-methyl-N-(3-(l-methyleihylamiiio)-2-pyridinyl)- amino)piperidine, l-[6-fluoroindolyl-2'Carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]- piperazine, l-[5,6-dimethoxyindolyl-2-carbonyl]-4-[3-ethylamino-2-pyridinyl]piperazine, N,N'-dimethyl-N-(indolyl-2-carbonyi)-N'-[3-(l-methylethyIamino)-2- pyridinyl]-2E-butylenediamine, N,N,-dimelhyl-N-(indolyl-2-carbonyl)-N'-[3-(l-methylethylamino)-2- pyridinyl]-2Z-butylenediamine, 2>21N,N,-letramethyl-N-(indolyI-2-carbonyl)-N'-[3-(l-methylethylamino)-2-pyridinyl]-1,3-propanediamine, N,N'-dimethyl-N-(indolyl-2*carbonyl)-N'-[(3-(l-methylethylamino)-2- pyridinyl]-3-oxa-l,5-pentanediamine, N,N',N*-trimethyl-N-(indolyl-2-carbonyl)-N*-[(3-(l-methylethylamino)-2- pyridinyl]diethylenetriamine, l-(6-cyanoindolyl-2-carbonyl)-4-[3-(ethylamino)-2-pyxidmyl]piperazine, l-(6-pyridylindolyl-2-carbonyl)-4-[3-(l-methylethylamino)-2- -134- pyridinyl]piperazine, l-(6-(l-pynolidinyl)indolyl*2-carbonyl)-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, 1 -(6-( 1 -pyrrolidinyl)indolyl-2-carbonyl)-4-[3-(ethylamino)-2-pyridinyl] piperazine, l-(6-dimethylaminoindolyl-2-carbonyl)-4-[3-(l, l-dimethylethylamino)-2-pyrazinyl]piperazine, l-[(6-dimethylaminoindolyl)-2*carbonyl]-4-[3-(l,l-dimethylethylamino)-2- pyridinyl]piperazine, l-[5-nitroindolyl-2-carbonyl]-4-[3-(l,l-dimethylethylamino)-2-pyridinyl]- piperazine, l-((6-hydroxymethylindolyl)-2-carbonyl]-4-[3-(l, l-dimethylethylamino)-2-pyridinyl]piperazine, l-[2-(5-(N’,N’-dimethylaminomethylene)aminoindolyl-2-carbonyl]-4-[3-(l,l- dimethylethylamino)-2-pyridinyl]piperazine, l-[(6-dimethylaminomethyl)indolyl-2-carbonyl]-4-[3-(l,l-dimethylethylamino)· 2-pyridinyl]piperazine. 13. A diaromadc substituted compound (III) according to claim 12 which is l-[indolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, l-[indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine, l-[5-fluoroindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, l-[5-fluoroindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]-piperazine, l-(5-fluoroindolyl-2-methyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine, l-(indolyl-2-carbonyl]-4-[3-(l,l-dimethylethylamino)-2-pyridinyl]piperazine, l-[5-fluoroindolyl-2-carbonyl]-4-(3-(lfl-dimethylethylamino)-2-pyridinyl]- piperazine, l-(5-fluoroindolyl-2-carbonyl)-4-[3-(l-methylethylaniino)-2-pyrazinyl]- piperazinc, N,N’-dimethyl-N-(indolyl-2-carbonyl)-N,-[3-(l-methylethylammo)-2-pyridyl]-1,3-propanediamine, l-[5-(carboxymethoxy)indolyl-2-carbonyl]-4-[3-(l-methyleihyl- amino)-2- -135- LV 10264 pyridinyl]piperazine, l-[3-methylindolyl-2-carbonyl]-4-(3-[l-methylelhylamino)-2- pyridinyl]piperazine, l-[indolyl-2-caibonyl]-4-(3-ethylamino-2-pyridinyl)-l,4-diazepine, 5 l-(indolyl-2-carbonyl)*4-[3*(l-methylethylamino)-2*pyridinyl]-l,4-diazepine, l-[2-(5N-(N,,N’-dimethylaminomethylene)aminoindolyl)carbonyl]-4-(3-(l-methylethylamino)-2-pyridinyl)piperazine, l-[5*(2’-aminoacetamido)indolyl-2-carbonyl]-4-(3-(l-methylethylamino)-2- pyridinyl)piperazine, 10 l-[5,6-methylenedioxyindolyl-2-carbonyl]-4-[3*(l-methylethylamino)-2-pyridin· yl]piperazine, l-[6-(N,N-dimethyIamino)indolyl-2-carbonyl]-4-[3-(l-methyleihylamino)-2* pyridmyl]piperazine, l-[indolyl-2*carbonyI]-4-[3-(l-ethylpropyl)amino-2-pyridinyl]piperazine, 15 l-[5-methanesuIfonamidoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, 1 -[5-fluoroindolyl*2-carbonyI]-4-[3-(2-meihoxy-1 -methylethylamino)-2-pyridinyl]piperazine, l-[6-fluoromdolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]· 20 piperazine. 14. An anti-AIDS piperazine (IV) selected from the group consisting of l-[4-methoxy-3,5-dimethylbenzoyl]-4-[3-(elhylamino)-2-pyridinyl]piperazine, l-[4-methoxy-3,5-diinethylbenzyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, 25 l-[4-hydroxy-3,5-dimethylbenzyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, l-I4-methoxy-3,5-dimethylbenzyl]-4-(3-(propylamino)-2-pyridinyl]piperazinel l-[4-methoxybenzyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, l-[5-methoxyindolyl-2-carbonyl]-4-(2-ethoxyphenyl]piperazinc, l-[5-methoxyindolyl-2-carbonyl]-4-(3-(ethylamino)-2-pyridmyl]piperazine, 30 l-[5-methoxyindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]- piperazine, l-[5-methoxyindolyl-2-carbonyl]-4-[2-(ethylamino)phenyl]piperazine, l-[5-hydroxyindolyl-2-carbonyI]-4-[3-(ethylamino)-2-pyridInyl]piperazine, -136- l-[5-hydroxyindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-methoxy-4,6,7-trimethylindolyl-2«carbonyl]-4-[3-(ethylainino)-2- pyridinyl]piperazine, 5 l-[5-methoxyindolyl-2-carbonyl]-4-[3-(l, l-dimethylethylamino)-2-pyridinyl]· piperazine, l-(5-methoxyindolyl-2-carbonyl)-4-[3-(methylamino)-2-pyridinyl]piperazine, l-[3,5-dimethyl-4-methoxybenzoyl]-4-[3-(ethylamino)-2-phenyl]piperazine, 1 -[3,5-dimethyl-4-methoxybenzoyl]-4-[3-( 1 -methylethylamino)-2-pyridinyl]-10 piperazine, l-[5-methoxyindolyl-2-methyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, l-(5-fluoroindolyl-2-carbonyl)-4-[3-(l-methylethylamino)-2-pyridinyl]-l,4- diazepine, N,N’-dimethyl-N-(5-methoxyindolyl-2*carbonyl)-N’-(3-(l-methylethylamino)‘2-15 pyridyl)ethylenediamine, l-[4-methoxy-3,4-dimethylbenzyl]-4-(3-(2-propenylamino)-2- pyridinyl]piperazine, N,N'-dimethyl-N-(5-methoxyindolyl-2-carbonyl)-N'-[3-(l*methyIelhylaniino)*2- pyridinyl]-2E-butylenediamine, 20 N,N'-dimethyl-N-(5-methoxyindolyl-2-carbonyl)-N,-[3-(l-methylethylamino)-2- pyridinyl]-2Z-butylenediamine, l-(5-methoxyindolyl-2-carbonyl)-4-[3-methylamino-2-pyridinyl]piperazine, l-(5-methoxyindoIyI-2-carbonyl)-4-[3-propylamino-2-pyridinyl]piperzine, l-(5-methoxyindolyl-2-carbonyI)-4-[3-(cyclo-propylmethylamino)-2-pyridinyl]-25 piperazine, l-(5-methoxyindolyl-2-carbonyl)-4-[3-(l, l-dimethylethylamino)-2-pyrazinyl]· piperazine and enantiomers, pharmaceuticaJly acceptable salts, hydrates and solvates thereof. 30 15. An anti-AIDS piperazine (TV) according to claim 14 which is l-[5-methoxyindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, l-[5-methoxyindolyl-2-carbonyl]-4-[3-(l-methylethylaraino)-2-pyridinyl]- piperazine, -137- LV 10264 l-[5-hydroxyindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyljpiperazine, l-[5-methoxyindolyl-2-carbonyl]-4-[3-(l,l-dimethylethylamino)-2-pyridinyl]- piperazine, l-(5-methoxyindolyI-2-carbonyl)-4-[3-(methylamino)-2-pyridinyl]piperazine. 16. An anti-AIDS piperazine (IV) according to claim 14 which is l*[5-methoxyindolyl-2-carbonyl]-4-(3-(ethylamino)-2-pyridinyl]piperazine. 17. A method of treating an individual infected with the human immunodeficiency virus (HIV) which comprises administering an effective amount of an indole of formula (V) where R,a is -CH2-,

(V) -CO-, •SOj-, -CHsCH-CO-, -COCHj-, where Z is

(Z-D where (I) Rj is =0 or Rj.j:Rm where one of Rm and R2.2 is -H and the other of R2., and R2.2 is -H or -CH„

Rj is =0 or Rj.i:Rj.2 where one of RM and RM is -H and the other of Rj., and RM is -H or -CHj, -138- R< is R^tR^ and Rj is Rj.,:Rj_2 where one of Ru and R4.2 is *H and the other of R*., and R^ is -H or -CH3, where one of RM and Rj.2 is -H and the other of Rs., and Rj.2 is -H or -CHj, (Π) R» is Rt-jiR*-* and Rj is Rj.3:Rs-4 where one of R^j and R^ and one of Rj.3 and Rj^ are taken together to form -CH2* and the other of R^j and R^, and Rj.3 and Rj^ are -H, R2 and R3 are (ΙΠ) R2 is R2.j:R2-i and Rj is Rj.3:Rj^ where one of R2.j and R2^ and one of Rj. j and Rj^ are taken together to form -CH2-CH2- and the other of R2.j and R2^, and Rj. j and Rj^ are -H, and R3 and R, are -H:-H, (IV) Rj is Rj.j:Rw and R* is R^Rj.* where one of Rj.j and Rw and one of R*. j and R^ are taken together to form -CH2-CH2- and the other of R^j and Rw, and R^ j and are -H, and R2 and Rs are -H:-H, -ViKCHAn-ZHCHjU-īr (Z-II) where n,, is 1 thru 5, 11¾ is 1 thm 5, Y, is -0-, -S-, ’N(Y|.i)- where Υ,., is Ci*C4 alkyl, 'C(Y|.z)(Yio) where Y,.2 and Y,.3 are the same or different and are -H or Cj-C4 alkyl, Y2 is -O-, -S-, "N(Y2.i)- where Y2-l is CrC4 alkyl, ~C(Y2-2)(Y2-3) where Y2.2 and Y2.3 are the same or different and are -H or Cj-C4 alkyl, Zļ is nothing (a bond), -0-, -S-, -N(Zj.,)- where Zj., is -H or C,-C4 alkyl, -C«C-, -CiZļ.^iZļ.ļ)- where Zļ.2 and Zj.j are the same or different and are -H or C,-C4 alkyl, cis and trans -CfZj.j)=0(2^)- where Zj.2 and Zj.j are the same or different and are -H or Cj-C4 alkyl, with the provisos (1) that when Yj is -O-, -S- or -N(Yj.i)-, then nn is 1 only when Zj is nothing (a bond), -C*C-, -C(Z2.2)(Z2.3)- or -C(Z3.2)=C(Z2.J)- and (2) that when Y2 is -O-, -S- or then nM is 1 only when Z2 is nothing (a bond), -C*C-, -C(Z2.2)(Z2.3)- or -C(Z2.2)=C(Z2.3)-, -139- LV 10264 (Ζ-ΠΙ) where n,2 is 1 or 2 and nl3 is 1 or 2, (Z-IV) where n,2 and nl3 are as defined above, /r-<CH2)Jll3 -N CB-y (Z-V) ^-<^2)al2 where Y3 is -N(Yj.,)- where YM is Ci-C4 alkyl and nu and nu are as defined above; Ki is -N=, -CH=, -N(0)=; R7a is -S-R7a., where R7A., is C,-C6 alkyl, -0-R7a.2 where R7A.2 is C,-Q alkyl, -C(R7A.ii)(R7A-i6)-(R7A.i7) where R7Mi and R7A.U are the same or different and are -H or C,-Cj alkyl and where R7A.,7 is Cļ-Cs alkenyl containing 1 or 2 double bonds or Cļ-Cs alkynyl containing 1 triple bond, -CO-R7A.u where R7A.j2 is -H,

Cj-Ci alkyl, CIfCt alkenyl containing 1 or 2 double bonds,

Cj-C^ alkynyl containing 1 triple bond, -CHj -φ, -φ optionally subsdtuted with 1 thni 3 -140- •CFj, C,*C4 alkyl, -OH, C,-Cj alkylthio, -0-C0-R7a.,2 where R7A.t2 is C,-Ce alkyl or -Φ, -F, -Cl, -Br, -CO-CF3, -NOj, -N(R7a.13)(R7a.„) where R7A.I3 and R7a.I4 are the same or different and are -H, C^Cj alkyl and where R7A.l3 and R7A.U are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisdng of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, -COO-R7A.n where R7a.u is as defined above, -CO-N(R7a.3)(R7aJ where R7a.3 and R7a4 are the same or different and are -H or C,-C6 alkyl, -N(R7a.j)(R7a J where R7A.S is C,-C4 alkyl, *CCR7A.ii)(^7A.j6)"0^7A.i7) where R7a.u>R7a-i6 and R7a-i7 are as defined above, -CH2-CH2-OH, -ch2-ch2-ch2-oh, -CH(CH3)CH2-0-CH3, -CH2-cyclopropyl, . -CH(CH3)CH2-OH, -ch2-cf„ -CH2-CH2F, -ch2-ch2-c«n, -CH-iCFi^-CTF^ where n,4 is 1 thru 5 and the carbon atoms marked with an asterisk 0 are bonded to each other to resulting in the formation of a ring, -(CHj)n,-N(R7A.7)(R7A4) where nt is 2 or 3 and where R7a.7 and R7A4 are the same or different and are -H 0r C,-C4 alkyl, and where ^7A-7 and R7A-1 are taken together with the attached nitrogen atom to form a heterocyclic ring selected -141- LV 10264 from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl, N-morpho-linyl, l-aziridinyl, and where R7A^ is -H, C,-C6 alkyl,

5 ’C(R7a.ij)(R7a.16)-(R7a.|7) whefe R7A.i5» &7Λ·1« ^<3 ^7Α·17 ST® ES defined above, -CHrCHrOH, -CHj-CHj-CHj-OH, -CHjCFj, 10 -CH2-CH2F, -ch2-ch2-c*n, or where R7a.j and &7A4 are taken together with the attached nitrogen atom to form a heterocycllc ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl, N-morpholinyl or l-aziridinyl, 15 *(CH2)„4-N(R7a.9)(R7a.,0) where n, is 1 or 2 and where R7A.9 and R7a.«o are the same or different and are -H or C,-C< alkyl, and where R7A.9 and R7A.i0 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1 -pyrrolidinyl, l-piperidinyl, l-piperazinyl or N- · morpholinyl, 20 R| is -N=, -CRm = where Rw is -H, -F, -Cl, -Br, -CF3, -NO* -C0CF3,

CrQ alkyl,

CpCj alkylthio, -OH, -0-Rj.j where RM is Ct-C6 alkyl, -Φ, -CO-Rw where Rw is Cj-Ce alkyl 25 or -φ, -NHiRn) where RM is CrQ alkyl, -€(Κμ7)(ΒΜ)-(Β4.9) where R*.7 and Rw are the same or different and are -H or Ci-Cj alkyl and where Rw is Cj-Cj alkenyl containing 1 or 2 double 30 bonds or C^-Cj alkynyl containing 1 triple bond, -NR^j-CO-R^ where Rw is -H or alkyl and Rw is -H, alkyl or Cj-Cj alkoxy; R* is -N= or -CR^.i= where R*., is -H, -F, -Cl, -Br, -NO* -CGCFJt -142- C,-C4 alkyl, C,-Cj alkylihiof -OH, -O-R^.2 where R*2 is C,-C6 alkyl, -φ, -CO-R*, where R,.3 is C,-C4 alkyl or -φ, with the proviso that R,.2 is not alkyl when R7 is -OR7.2, *Ν(Κ^)(Κ^ί) where R^ and R^j are the same or different and are -H, Cj-Ce alkyl, -0(^.1)(119.9)-(1^.10) where R*., and R9.9 are the same or different and are -H or C,-C} alkyl and where R^jo is C2-Cj alkenyl containing 1 or 2 double bonds or C^-Cj alkynyl containing 1 triple bond, R^4 and R9.5 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisdng of l-pyrrolidinyl, 1-piperidinyl, l-piperazinyl or N-morpholinyl, -NR^-CO-R*.? where R^ is -H or C,-C4 alkyl and R9.7 is -H, C,-C4 alkyl or Cj-Cj alkoxy;

Rl0 is -N= or -CRļo-i = where Rl0., is -H, -F; -Cl, -Br, -CF3, -NO^ -COCF3, CrQ alkyl, C,-Cj alkylthio, -OH, -0-Rio.j where Rl0.2 is C,-C4 alkyl, -φ, -CO-R,M where Rl0.3 is Ci*C4 alkyl or -φ, -N(Ri(m)(Rio.j) where R1(M and R10.J are the same or different and are - H* C,-Q alkyl, -C(Rio.i)(Rio.9)-(Rio.io) where Rl0.j and R,o.9 are the same or different and are -H or Q-C3 alkyl and where R10.,0 is CVC* alkenyl containing 1 or 2 double bonds or Cj-C3 alkynyl containing 1 triple bond, -NR,m-CO-Rio.7 where RiM is -H or Cj-C4 alkyl and R10.7 is -H, C,-C4 alkyl or C,-Cj alkoxy, with the proviso that not more than two of R4, Rlt R, and R,0 are -N=; where ^ is a single or double bond;

Qi is -NX„ where Xu is -Η, -$02-φ, -S02-CH3, -CO-Xu.i where X,,., is Ct-C4 alkyl, -CF3 or -φ; LV 10264 -143- Xl7 is -H or -CH3; X.. is -H or -CHj; Χ.9 is -H or -CH3; x» is -H, 0,-04 alkyl, -00-(0,-04 alkyl), -CH2-4>, -CO-Φ or -prodrug where prodrug is -PC^-O· cation"·, • -C0-CH2-C0-NH-CH2-S02-0' cation+, -CCHCHjtaj-Rji where n21 is 1-7 and RM is -COO'****+· -NR3l.1R51.2 where Rs,., and RJt.2 are the same or different and are -H or C,-C3 alkyl, -N+Rj,.iRj,.2RM.jhalide· where R51.„ RS1.2 and R31.3 are the same or different and are -H or C,-C3 alkyl, and where halide is -C1 or.-Br, -CO-CH(amino acid)-NH2 where amino acid is -H, -CH3, -CH(CH3)2, -CH2-CH(CH3)2l -CH2-OH, -CH(OH)(CH3), -CH2-φ, -CH2-[p-hydroxyphenyl], -CH2-[3-indolyl], -CHj-S-S-CHj-CHfNH^-COOH, -CH2-SH, -CH2CH2-S-CH3, -CH2-COOH, -CH2-CO-NH2, -CH2-CH2-COOH, -CHj-CH2-CO-NH2, -ΟΗ2-[2-ΗΙ5Ήϋ YL], -(CH2)3-NH-C(NH)-NH2, -(CH^-NHj, -CH2-CH2-CH(OH)-CH2-NH2i -(CH^-NHj, -(CH^-NH-CO-NHj -CH2CH2-OH, -CO-CH=CH-CO-O' cation+, -CO-N*-CH=CH-N=CH* where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring, -CO-C*=C[(CH2)b22-NH2]-CH=CH-CH=CH* where na is 1 or 2 and where the atoms marked with an asterisk 0 are bonded to each other resulting in the formation of a ring, -CO-C*=CH-CH=C(-NR32)-CH=CH* where Rn is -H or C,-C3 alkyl and where the atoms marked with an asterisk 0 are bonded to each other resulting in the formation of a ring, -CCMCHj^-CO-CMOHļA sugars], -C0-0-CH(CH2-0-C0-RJ3)2 where the R33’s are the same or different and are C|-C1$, -C0-(CH2)4-C0-N(CH3)-CH2-CH2-S03*catioa+, -CH2-0-C0-(CH2)ft2,-NRjl.lRJ1.2 where n2l, R3M and R31.2 are as defined above, -CO-NH-OH^-Rjj where R33 is -H or C,-C, alkyl, -NO^ -NR5i.,Rii.2 where R3,., and R31.2 are as defined above; with the proviso that R, is not -CH2- when -144-

Ri7, Rm and R19 are ali -CH3; and enantiomers, pharmaceutically acceptable salts, hydrates and solvates thereof. 18. A method of treating an individual infected with the human immunodeficiency virus (HIV) according to claim 17 where the infected individual is asymptomatic but tests positive for the HIV antigen. 19. A method of treating an individual infected with the human immunodeficiency virus (HIV) according to claim 17 vvhere the infected individual is symptomatically sick but does not have "full blown AIDS". 20. A method of treating an individual infected with the human immunodeficiency virus (HTV) according to claim 17 who has "full blown AIDS", 21. A method of treating an individual infected with the human immunodeficiency virus (HTV) according to claim 17 where the administration is oral. 22. A method of treating an individual infected with the human immunodeficiency virus (HTV) according to claim 21 where the effective dose is firom about 0.10 mg/kg/day to about 500 mg/kg/day. 23. A method of treating an individual infected with the human immunodeficiency virus (HIV) according to claim 17 vvhere the administration is in combination with AZT or other and-virals. 24. A method of treating an individual infected vvith the human immunodeficiency virus (HTV) according to claim 17 vvhere the indole is l-[5-methoxyindoIyl-2-carbonyl]-4-(3-(ethylamino)-2-pyridinyl]piperazine. 25. l-[Indolyl-2-carbonyl]-4-(3-nitro-2-pyridinyl)piperazine, (P10) l-[5-fluoroindolyl-2-carbonyl]-4-[(3-nitro)-2-pyridinyl]piperazine, (P17) l-[indolyl-2-carbonyl]-4-[3-amino-2-pyridinyl]piperazine> (P22) P35 N,N’-dimethyl-N-(indolyl-2-carbonyl)-N’-(3-nitro-2-pyridinyl)ethylenediamine, -145- LV 10264 P37 2-(N-methyl-N-(3-nitro-2-pyrid-2-yl)amino)ethylindole-2-carboxylatel P129 1 -[5-fluoroindolyl-2-carbonyl]-4-(3-amino-2-pyridinyl]piperazine. 26, A method of treating an individual infected with the human immunodeficiency 5 virus (HIV) which comprises administering an effective amount of an anti-AIDS amine of formula (X) 10 (X)

R7B

[Aryl/Heteroaryl]-Rjg-

where Ria is -CH2-, 15 -CO-, where Z is

where (I) R2 is =0 or R2.,:R2.2 where one of R2., and R2.2 is *H and the other of R2.t 25 and R2.2 is -H or -CH3,

Rj is =0 or Rj.,:Rļ.j where one of Rw and RM is -H and the other of Rj.j and R« is -H or -CHj, R* is R^rR^ and R3 is R^R^ where one of R^, and R^ is -H and the other of Ru and R*.2 is -H or -CHj, where one ofRM and Rj.2 is -H and the other of Rj.t 30 and Rj.2 is -H or -CH3, (Π) R« is R^rR*^ and R} is Rj^tR^ where one of R<.3 and R^ and one of Rj.3 and Rw are taken together to form -CH2- and the other of R+.3 and Rm, and Rj.3 and Rm are -H, R2 and R3 are -H:-H, -146- (ΠΙ) R: is R2.j:Rw and Rj is Rj.5:Rm where one of Rw and Rw and one of Rj. s and Rw are taken together to form -CH2*CH2- and the other of R2.3 and RM, and Rs. 5 and Rw are -H, and R3 and R< are (IV) R3 is Rj.5:Rw and R, is R^Rj-e w^ere one of Rj., and Rw and one of R*. s and R^ are taken together to form -CH2-CH2- and the other of Rj.5 and Rw, and R*. 3 and R^ are -H, and R2 and R3 are •VrCCH^n-Zj-CCH^-V,- (Z-II) where n„ is 1 thru 5, nM is 1 thru 5,

Yj is -0-, -S-, -N(Y!.0- where YM is CrC4 alkyl, C(Yi-ī)(Yi.j) where Y,.2 and Υ,ο are the same or different and are -H or Cj-C* alkyl, - Y2 is -0-, -S-, *N(Yj.i)· where Y2.j is Ct-C4 alkyl, -C(Ym)(Yw) where Y2.2 and Y2.3 are the same or different and are -H or C,-C4 alkyl, Zļ is nothing (a bond), -O-, -S-, -NCZj.,)- where Zj., is -H or C,-C4 alkyl, -C»C-, •C(Z2.2)(Z2.j)- where Z^ and Z^ are the same or different and are -H or Cj-C4 alkyl, cis and trans -C(Z2.2)=C(Z2.3)- where Zj.j and Zj.3 are the same or different and are -H or CrC4 alkyl, with the provisos (1) that when Yj is -0-, -S- or ’N(Y|-i)-* then n„ is 1 only when Z2 is nothing (a bond), -C«C-, -C(Z2.2)(Z2.3)· or -C(Z2.2)=C(Z2.3)- and (2) that when Y2 is -Or, -S- or -N(Y2.,K then nM is 1 onIy when Zļ is nothing (a bond), -OC-, -CfZjJCZjj)- or -C(Z2.2)=C(Z2.3)-, Γ~(fB2>ū12 - ī w — (z-m) where nl2 is 1 or 2 and nl3 is 1 or 2, 147- LV 10264 (Z*IV) —CCH2>fti2 ^C^2)n13 5 where n12 and nu are as defined above,

(Z-V) 10 wherc Y, is -N^)- where Yw is C,-C4 alkyl and n,2 and nl3 are as defined above; where R* is -N=, -CH=, 15 R7B is -CO-R^n where R7B.n is -H, C,-Q alkyl, C^-Ce alkenyl containing 1 or 2 double bonds, Cļ-06 alkynyl containing 1 triple bond, -CHj-φ, 20 -φ optionally substituted with 1 thru 3 "CFJf C,-C4 alkyl, -OH, C,-Cj aIkylthio, 25 “0"C0”R7^j2 where R7B.11 is Cj_C4 alkyl or ·φ, -F, -Cl, -Br, -CO-CFj, -NO,, -N(R7B.,3)^,0 where R^u and R^m ite the same or 30 different and are -H, C1-C3 alkyl and Where R^j and R^ are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1 -pyrroIidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, •S-R-tb-i where R?m »s C,-C, alkyl, -148- -O-Rtb-j where Rtb.2 is C,-C6 alkyl, -CCR7B.15)(R7B.16)-CR7B-I7) where R^.,, and Rv^e are -H, or C^Cj alkyl and R^ π is C2-C} alkenyl containing 1 or 2 double bonds or C2-Cs alkynyl containing 1 triple bond, R, is -N=, -CH= R, is -N=, -CH=

Rl0 is *N=, -CH= with the proviso that not more than two of R*, Rs, R* and R,0 are -N=; and where aryl/heteroaryl is a substituent selected from the group of substituents of formula (l) (1) uo where X, is -H, Ci-C4 or n-alkyl, X2 is -H, Ci*Q or n-alkyl, X3 is Ci-Cj alkyl, -CO-Xj., where Xj., is Cj-C4 alkyl or -φ, -CH2-φ, -Φ; ... of formula (2)

where X4 and X4 are the same or different and are -H, C,-C4 alkyl, -(CH^-N^JO^t) where n5 is 2 or 3 and where Χ^ι and X4.2 are the same or different and are -H or C,-C4 alkyl or where X*.| and Χ*.2 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, -149- LV 10264 and where X* and X5 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, 1- piperidinyl, l-piperazinyl or N-morpholinyl, and where X, and X2 are as defined above, with the proviso thāt both X* and > 5 X5 are not both -H; ... of formula (3)

H

10 where 15 X* is -H, C,-C, alkyl, -F, -Cl, Br, -OH, -0-CH2-^, -0-CF3f -0-CH2-C00X*.,4 where Χ<.Μ is -H, C,-C* alkyl, -φ, -CH2-φ, -CHO, Cļ-Cļ alkoxy, C,-Cj alkylthio, -O-CO-Χ*., where Χ^ is -H, C,-C4 alkyl οτ ·φ, -O-SOj^jj where X*.|2 is Cj-C4 alkyl, -COO-Χί,υ where X*.i3 is -H, C,-C4 alkyl, -Φ or -CH2-tf>, 25 -C*N, *NOj, -N3, -NX4.,0X4.u where Χ^ο and Χ<.η are the same or different and are -H or C,-C3 alkyl or where Χ^,,ο and X*.,, are taken together with the attached 30 nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, l-piperidinyl, l-piperazinyl, N-morpholinyl or l-aziridinyl, -ΝζΧ^χεΗ^-ΝζΧ^ζΧ^) where n3 is 2 thru 5, X*.2 is -H or CM alkyl, X*., is -H or CM alkyl, X^ is -H or CM alkyl, or where Xw and -150-

Xn are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl, N-morpholinyl or l-aziridinyl, -O-CO-fCH^-COOH, where n3 is as defined above, where n3, X*.3 and are as defined above, -(CH^-OH, where Π24 is 1 thm 5, where n« is 1 thru 5 and X«.j and are the same or different and are -H, C,-C4 alkyl or where Χ«.3 and X« are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinylf -NH-SOj-^ vvhere is Ct-C4 alkyl, C3-C7 cycloalkyl, -Φ or -CU2-4>, -N=C(Xm)-N(X4.7)(X«) where (a) is C,-C4 alkyl, C3-C7 cycloalkyl or -φ and where and X*.7 are as defined above, (b) X^7 and XM are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, (c) X^4 and X^7· are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrroIidinyl or l-piperidinyl, -ΝΧ^-ΟΟ-Χ*., where X^, is -H, Q-C4 alkyl or -φ· and where X^4 is as defined above, -O-prodrug where prodrug is -ΡΟ2-Ο·03ϋοη+, •CO-CHj-CO-NH-CHrSOj-O· cation*, -CCHCHjtai-Rj! where n2l is 1-7 and R31 is -COO' cation+, -NRjj.jRii.j where R31., and R„.2 are the same or different and are -H or C,-^ alkyl, -N+Rjl.iRji.2R31.3halide· where R3l.i, R},.2 and R5,.3 are the same or different and are -H or C3-C3 alkyl, and where halide is -C1 or -Br, -CO-CH(amino acid)-NH2 where amino acid is -H, -151* LV 10264 -CHj, -CH(CH3)2, -CH2-CH(CH3)2, -CHrOH, -CH(OH)(CH3), -CHr4>, -CHr[p-hydroxyphenyl], -CH2-[3-indolyl], -CHj-S-S-CHj-CHCNH^-COOH, -CH2-SH, -CH2CH2-S-CH3, -CHrCOOH, -CH2-CO-NH2, -CH2-CH2-COOH, -CH2-CH2-CO* NH2, -CH2-[2-HISTIDYL], -(CH^-NH-CiNHl-NH* -(CH^-NHj, -CH2-CH2* 5 CH(OH)-CH2-NH2, -(CHJj-NHj, -(CHjJj-NH-CO-^ -CH2CH2-OH, -CO-CH - CH-CO-O' cation+, -CO-N*-CH=CH-N=CH* where the atoms marked with an asterisk 0 are bonded to each other resulting in the formation of a ring, -CO-C*=C[(CH2)a23-NH2]-CH=CH-CH=CH* where nn 10 is 1 or 2 and where the atoms marked with an asterisk 0 are bonded to each other resulting in the formation of a ring, -CO-C*=CH-CH=C(-NR52)-CH=CH* where RJ2 is -H or Cj-C3 alkyl and where the atoms marked with an asterisk 0 are bonded to each other resulting in the formation of a ring, 15 -CCHCHjJ.jrCO-O-iCiH.A sugars], -CO-OCH(CH2-OCO-RJ3)2 where the R53’s are the same or different and are Cj-Cjj, -CCHCH^-CO-NCCH^-CHj-Ci^-SOj-cation*, -CH2-0-C0*(CH2)e2i*NR5,.,RJI.2 where n2j, R3j.j and R3ļ.2 20 are as defined above, -CO-NH-CJFVRjj where RJ5 is -H or Cj-C3 alkyl, -N02, -NRj,.,Rm.2 where RJM and R}1.2 are as defined above, -ΝΧ^-prodrug where and prodrug are as defined above 25 except that prodrug is not -P02-0·, 1¾ is 1 thru 3, the ^’s can be the same or can be different and where when n2 is 2 and the two groups are ortho to each other they can be takēn together to form -0-CH2-O; with the proviso that if n2 is 2 or 3, only one of the V* can be a prodrug, ... of formula (4)

<«> 30 -152- where Q, is -NX„.where X„ is -H, -S02-<t>, -SOj-CHj, -CO*Xu.j where X,,., is C,-C4 alkyl, -CFj or -<t>\ Qļ is -N« provided Rt is not -CH2-, -CX,2= where X,2 is -COO-X12., where X12., is -H or C,-C4 alkyl, -CO-N(X,2.J(Xi2.}) where X,2.2 and X,2.2 are the same or differeņt and are -H, Ct-C4 alkyl or where X,2.2 and Χ,2.2 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, -CO-COO^u., where X12., is as defined above, Cļ-Cj alkyl, -CO-φ, . -CO-X,2.j where X,2., is as defined above, -CO-CO-Npču.^pCu.j) vvhere X,2.2 and X,2.3 are as defined above, -(CH^-OH where.n23 is 1 or 2, and vvhere X« and n2 are as defined above, ... of formula (6) “

OgL «·> ... of formula (7)

(7) where ^ is a single or double bond, X,4 is -H, -O-CHj-ψ, -O-CFj, -153- LV 10264 -0-CH2-COOR14.io where Rl4.i0 is -H, C,-C4 alkyl, ·φ or -CHj-φ,

CrC. alkyl, -F, -Cl, Br, where Χ^ι is Ct-C4 alkyl, -C-N, -CHO, -(CH^-OH where n^ is 1 thru 5, -NQ„ *NHj, -Nj, -NH-CH2-tf>, -NH-S02-Xi4.i where Xl4.t is C,-C6 alkyl, C3-C7 cycloalkyl or -φ, where n3 is 2 thru 5, Xl4.2 is -H or CM alkyl, X14.3 is -H or CM alkyl, X1M is -H or CM alkyl, or where X14.3 and Xl44 are taken together with the attached nitrogen atom to form a heterocyclic ring selected fforn tlie group consisting of l-pyrrolidinyI, l-piperidinyl, l-piperazinyl or N-morpholinyl, -NXJ4.l3Xt4_M where X14.l3 and Xl4.,4 are the same or different and are -H or C,-Cj alkyl or where X14.j3 and Xl4.J4 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N*morpholinyl, -(CH^-NpC^j)^^) where n« is 1 thru 5 and X14.j and Χια are the same or different and are -H, Q-C4 alkyl or where and X:u are taken together with the attached nitrogen atom to form a heterocycļic ring selected from the group consisting of l-pynolidinyl, l-piperidinylf l-piperazinyl or N-morpholinyl, -N=C(X144)-N(XI4.7)(Xl4a) where (a) Xl4.7 and X144 are C,-C6 alkyl, Cj-C; cycloalkyl or -φ, where X1M is as defined above, (b) X14_7 and X144 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l-piperazinyl or N-morpholinyl, (c) Xim and X14.7 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pynrolidinyl or l-piperidinyl, -C0-0-XJ4.7 where Xl4.7 is as defined above, -154- -ΟΟ-ΝζΧ,^ίΧ^,) where Χ14.7 and Χ14., are as defined above, *N(Xu.2)-CO-Xl4., where Xl4.9 is -H, CfC4 alkyl or -Φ where Xl4.2 is defined above, *N(Xu.j)-prodrug, where prodmg is as defined above except that it is 5 not -P02-0\ and when Xl4.2 is as defined above, iv, is 0 thru 2, X* and Qj are as defined above; of formula (8) 10 *22

where X2, is -H, C,-C4 alkyl, -CO-(C,-C4 alkyl), -CH2-<t>, -CO-ψ or -prodrug where prodrug is as defined above,

Xn, Xjļ and XM are the same or different and are -F, -Cl, Br, 20 -OH, -O-CHj-φ, -O-CF3, -O-CHj-COOH, C,-Cj alkoxy,

Cj-Cj alkylthio, -0-C0-X2., where ΧηΛ is -H, Ci-C4 alkyi or -4, -NO,, -NHj, -N3, 25 -C«N, -NXn.I(CH2)e9-N(X22.})(X22J where n, is 2 thru 5, X2.2 is -H or CVC4 alkyl, X2.3 is -H or CrC4 alkyl, X24 is -H or Cj-C4 alkyl, and vvhere X2.3 and X24 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisdng of l-pyrrolidinyl, l-piperidinyl> l-piperazinyl or N-30 morpholinyl, •O-CO-iCH^-COOH, where % is as defined above, •0"(CH^,9*N(X2.j)(X24) where η^, X2.3 and Xjj4 are as defined above, -155- LV 10264 (CHj),ļo*N(X22.j)(X22^) where is 1 thru 5 and Xj2-j and 2X6 thc same or different and are -H, C,-C4 alkyl and where X2.j and XK^ are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of l-pyrrolidinyl, l-piperidinyl, l*piperazinyl or N-morpholinyl, 5 -Ν(Χη.7)(Χη4) where Xu.7 and Xn4 are C,-C6 alkyl, C3-C7 cycloalkyl or -ψ, and where any adjacent two of -0-X2h Χ^, Xa or XM are taken together to form a methylenedioxy group (-0-CH2-0-),

Qi and ^ are as defined above; 10 ... of formula (9)

*11 (9) 15 where X,0 is -H, -F, -C1 or -Br,

Qj is -CH= or Q2 where (¾ is as defined above, X« and X„ are as defined above; 20 ... of formula (10)

(10)

25 XH where X<1 Xu and Qj are as defined above; ... of formula (11)

(11) 30 *7 -156- where X7 is -H, -S02*tf>, -S02-CH3, -CO-X7.i where X7.| is C,-C4 alkyl or -φ, X, is -H, C,-C6 alkyl, -CH2-φ, -SOj-φ, -$02-CH3l -CO-Xn where XM is C|-C4 alkyl or -φ, I. ^ is as defmed above; ... of formula (15)

(15) where (¾ and Xn are as defmed above; ... of formula (16)

(16) where Qj and Xn are as defmed above; ... of formula (17)

(17) where Qj and Xn are as defmed above; ... of formula (18)

where (¾ and XM are as defmed above; (18) -157- LV 10264 ... of formula (19)

(19) vvhere Qj and X„ are as defmed above; ... of formula (20)

(20) 15 vvhere Qj and X„ are as defmed above; ... of formula (21)

(21) vvhere Ql, X6 and n7 are as defined above, enantiomers, pharmaceutically acceptable salts, hydrates and solvates thereof. 25 27. A method of treating an individual infected with the human immunodeficiency virus (HTV) according to claim 26 vvhere the (1) infected individual is asymptomatic b>ut tests positive for the HTV antigen, (2) infected individual is symptomatically sick but does not have ’full blovvn AIDS", (3) individual infected with the human 30 immunodeficiency virus (HTV) has "full blovvn AIDS". 28. A method of treating an individual infected with the human immunodeficiency virus (HTV) according to claim 26 vvhere the administration is oral and the effective -158- dose is from about 0.10 mg/kg/day to about 500 mg/kg/day. 29. A method of treating an īndividual infected with the human immunodeficiency vīrus (HIV) according to claim 26 where the anti-AIDS amine (X) is l-[indolyI-2-5 carbonyl]-4-[2-ethoxyphenyl]piperazine.

Claims (29)

1. Diaryl or diheteroaryl-substituted compounds of the general formula (III): m wherein R 1 is -CH 2 -, -CO-, -CO-CH 2 -, -SO 2 - or -CH = CH-CO-; Z is one of the following groups; hh (ZI) wherein: (I) R2 is oxygen or R11 and R2.2, wherein one of R2 and R2.2 is hydrogen and the other of R1 and R2.2 is hydrogen or methyl, R3 is oxygen or R3, and R3.2, wherein one of Rl and R3.2 is hydrogen, and the other of R3l and R3.2 is hydrogen or methyl, R4 is R4.1 and R4.2, and R5 is R6 and R5.2 where one of R4t and R4.2 is hydrogen and the other of R4 and R4.2 is hydrogen or methyl, one of R6 and R6 being hydrogen and the other of R6 is hydrogen. and R 1 is hydrogen or methyl, (II) R 4 is R 1 and R 6 is R 5 is Rw and RW 1 wherein one of R 4.3 and R 4 and one of R 5.3 and R 5.4 together form a methylene group, but the rest of R4.3, R4.4, and R5.3 > RMi is hydrogen; R2 and R3 are hydrogen atoms; -H, (III) R2 is R2.5: R2 ^ and R5 is R5.5: R5.6l where one of R2.5 and R2.6 and one of R5.5! R5.6 together form the ethylene -CH2-CH2- group and the other of R2.5 and R2_g and R5.5 and R5.6 are hydrogen; R3 and R4 are -Η; -H, (IV) R3 is R3.5: R3.6 and R4 are R4.5) R4, wherein one of R4.5 and R4.6 together forms an ethylene group -CH2-CH2- and the other of R3.5 and R3_e and R4.5 and R @ 1 are hydrogen; R2 and Rs are hydrogen atoms; -H, -Yr (CH2) n, rZ2- (CH2) n26-Y2- (Z-11) wherein n1 = 1-5, n26 = 1-5, Y1 oxygen, sulfur or -ΝßΥ ^) - wherein Υ ^ is C--Cil alkyl- ΟΟΥΥχΥχΥ) - wherein Yt.2 and YM are the same or different and denotes hydrogen or C1-C4 alkyl; Y2 is an oxygen or sulfur atom, the group -N (Y2 ..) - wherein Y2i is C1-C4 alkyl; -C (Y2.2) (Y2.3) -, wherein Y2.2 and Y2.3 are the same or different and represent a hydrogen atom or a -C4 alkyl group; A Z2 chemical bond, an oxygen or sulfur atom, a group -NFZ1-, - wherein Z2r is hydrogen or C1-C4 alkyl, -OC-; -C (Z2.2) (Z2.3) -f wherein Z2.2 and Z2.3 are the same or different and represent a hydrogen atom or a C1-C4 alkyl group; 2 LV 10264 cis- and trans- -0 (Ζ2.2) =: 0 (Ζ2.3) - where Z2.2 and Z2.3 are the same or different and represent a hydrogen atom or a C 1 -C 4 -alkyl group; provided that 1) when Y1 is an oxygen or sulfur atom or a group -N (Ym) -. nn = 1 only if Z2 is a chemical bond or a -CsC- group; -C (Z2.2) (Z2) -, -C (Z2.2) = C (Z2) -; and 2) when Y2 is an oxygen or sulfur atom or a group -N (Y2-i) - n26 = 1 only when Z2 is a chemical bond or -OC-; -C (Z2.2) (Z2) -, -C (Z2.2) = C (Z2.3) -; / -CPB2 ^ ft12 - K K-V < A >! 3 'where n12 = 1 or 2 and n13 = 1 or 2; where κ ch_ »WcE2) fti2 3 ~ (Z" V > n12 and n13 have the above meanings; where Y3 is a group -N (Y3_i) - wherein Y3t is a C1-C4 alkyl group, and n12 and n13 have the above meanings ; Re is nitrogen, grop -CH = or -N (O) =; R7 is -COO-R7.n are above -CO- N (R7.3) (Rm) where R7.3 and R74 are is the same or different and represents a hydrogen atom or a C 1 -C 6 alkyl group; 3 - N (R 7.5) (R 7-6) wherein R 7.5 is C 1 -C 6 alkyl, C (R 7i 5) (R 7i 6) - (R7.17) wherein R7.15 and R7.16 are the same or different and represent -H or C1-4alkyl of a hydrogen atom and wherein R7.17 is a C2-C5 alkyl group with 1 or 2 double bonds or C2- C5-alkynyl with one triple bond, -CH2-CH2-OH, -ch2-ch2-ch2-oh, -CH- (CH3) CH2-O-CH3 -CH- (CH3) CH2-OH -ch2-cf3, -CH2-cyclopropyl, -CH2-CH2F, -CH2 -CH2-C = N, -C * R7.18- (CH2-) n14-C * H2, wherein R7-18 is hydrogen -H or methyl-CH3i n14 is 1- 5, but the carbon atoms with an asterisk (*) are linked together to form a ring - (CH 2 -) n N (R 7 -) (R 7e) wherein R 2 = 2 or 3, and R 7.7 and R 7 are the same or different and represent a hydrogen atom -H or C 1 -C 4 alkyl, or R 7.7 and R 7 together with the nitrogen atom to which they are attached forms a heterocyclic ring, which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl or 1-aziridinyl; R7.6 is hydrogen, CVC8 alkyl or -C (R7.15) (R7.16) - (R7.17) wherein R7 is. 15, R7.16 and R7.17 have the above meanings and R7.17 may also include -CH2-CH2-OH, -ch2-ch2-ch2-oh, -ch2CF3i -ch2 -ch2f, -ch2 - ch2-c = n, or R7.5 and R7.6 together with the added nitrogen atom form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl or 1-aziridinyl, · - ( CH2) n4-N (R7.9) (R7.10) wherein n4 = 1 or 2 and R7.9, R7.10 are the same or different and represent hydrogen or C1-C4 alkyl, or R7.9 and R 7.10 together with the added nitrogen atom form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl; 4 LV 10264 R8 is a nitrogen atom, -CR8 is = where R8 is hydrogen, fluorine, chlorine, bromine, trifluoromethyl, nitro, trifluoroacetyl, C1-C6 alkyl, C1-C8 alkylthio, hydroxy, -OR8 .2, where R8.2 is C1-C6-alkyl, phenyl, -COR8.3 where R8.3 is C1-C6-alkyl or phenyl, -NHR8.4 where R8-4 is C1-C6-alkyl, -C (R8.7) ) (R8.8) - (Re-g). wherein R8.7 and R8-8 are the same or different and represent hydrogen or C1-C3 alkyl, and R8.9 C2-C5 alkynyl having 1 or 2 double bonds or C2-C5 alkynyl with one triple bond, -NR8.5-CO- R8, wherein R8.5 is hydrogen, C1-C6-alkyl or C1-C3-alkoxy; Rg is a nitrogen atom or a group -CR9.l =, wherein R8 is hydrogen, fluoro, chloro, bromo, nitro, trifluoroacetyl, C1-C6-alkyl, C1-C3-alkylthio, hydroxy, -OR9.2, where R9. 2 is C 1 -C 8 -alkyl, phenyl, -COR 9 -, wherein R 9.3 is C 1 -C 6 -alkyl or phenyl, -N (R 9.4) (R 9.5) wherein R 9.4 and R 9.5 are the same or different and represents a hydrogen atom or a C 1 -C 6 alkyl group, -C (R 9.8) (R 8 -g) - (R 8 -o). wherein R9.8 and R9.9 are the same or different and represent hydrogen or C1-C3 alkyl, and R9.10 is a C2-C5 alkynyl group having 1 or 2 double bonds or a C2-C5 alkynyl group with one triple bond, R9_4 and R9-5 together with the nitrogen atom attached thereto forms a heterocyclic ring, which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, -NRg.6-CO-R9.7, wherein R9 is hydrogen. , C 1 -C 6 -alkyl and R 9.7 are hydrogen, C 1 -C 6 -alkyl, or C 1 -C 3 -alkoxy; R10 is a nitrogen atom or a group -CR 6, which is hydrogen, fluorine, chlorine, bromine, trifluoromethyl, nitro, trifluoroacetyl, C 1 -C 6 alkyl, C 1 -C 8 alkylthio, hydroxy, -OR 10.2, where R 10.2 is C 1 -C 6 -alkyl or phenyl, -COR 4 -C 3 wherein R 10.3 is C 1 -C 6 -alkyl or phenyl, -N (Rkm) (in Rio). wherein R1 (M and R10.5 are the same or different and represents a hydrogen atom or a C1-C6 alkyl group, C (R10-e) (Rio-g) - (R10-10) wherein R11a and R10.9 are identical or different and denotes hydrogen or C 1 -C 3 alkyl, and R 10 represents C 2 -C 5 alkenyl having 1 or 2 double bonds or C 2 -C 5 alkynyl with one triple bond, -NR 10.6-CO-R 10. 7. wherein R1CM5) is hydrogen or Ct-C6-alkyl and R10.7 is hydrogen, C1-C8-alkyl or C1-C3-alkoxy; provided that no more than two of the radicals R6i R8i R9 and R10 are nitrogen; Aryl / heteroaryl is a substituent selected from the group consisting of: (1) h where and X2 is hydrogen, C1-C8-alkyl- or n-alkyl, X3 is C1-C6-alkyl or -ΟΟΧ ^ (where Χ3.1 is C1-C4-alkyl or phenyl), benzyl, phenyl, phenyl ; substitute formula (2) wherein X4 and X5 are the same or different and denote hydrogen, C1-C4 alkyl, (CH2) n5-N (X4.1) (X4.2) wherein ns = 2 or 3 and wherein Χ ^ and X4.2 is the same or different and represents a hydrogen atom or a C 1 -C 4 alkyl group, or X 4, and X 4.2 together with the nitrogen atom to which they are attached form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N morpholinyl; X4 and X5 may be taken together with them to form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl; Xt and X2 are as defined above, provided that both X4 and X5 are not simultaneously hydrogen; substitute of formula (3) LV 10264 E where Xg is hydrogen, fluorine, chlorine, bromine, C1-C4-alkyl, hydroxy, methoxyphenyl, trifluoromethoxy, -O-CH2-C00Xe.14, where Χβ.14 is hydrogen, C1-C6-alkyl, benzyl, phenyl, -CHO, C1-C3-alkoxy or C1-C3-alkylthio, -O-C0-X6.1t where Χβ., is hydrogen, C1-C4-alkyl or phenyl-, -O-SO2-X6.12, wherein Χρ.12 is C 1 -C 4 alkyl, -OCO-X 6.13, wherein X 6.13 is hydrogen, C 1 -C 6 alkyl phenyl phenyl or benzyl; cyano, nitro, N3, -N (Xe.io) (X6-ii) wherein X6.10 X6.1t is the same or different and represents a hydrogen atom or a C1-C5 alkyl group, or X6.10 and X6. n together with the attached nitrogen atom forms a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl or 1-aziridinyl, -N (X6.2) (CH2) n3-N ( X6.3) (Χ ^), where n3 = 2-5, Χβ.2 Χ ^, and XM are hydrogen or C1-C4 alkyl, or Χβ_3 and XM together with the nitrogen atom attached to them form a heterocycle ring may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl or1-aziridinyl, -OCO- (CH2) n3-COOH, where n3 is defined above, -O- (CH2) n3-N (X6.3) (Χβ-4) »where n3, Χβ.3ι and X ^ have the meanings defined above, - (CH2) n24-OH, where n24 = 1-5, - (CH2) n6-N (X6.5) (Χβ ^ ), where n6 is 1-5 and Χβ_5 υηΧβ.6 is the same or different and denotes -H, C 1 -C 6 alkyl, where Χβ_5 and X 1 together with the s a nitrogen atom forms a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl, -NH-SO2-Xe.7, wherein Xe.7 is a C1-C4 alkyl group, a C3-C7-cycloalkyl group; , phenyl or benzyl, -N = C (X6.4) -N (X6.7) (X6.8), wherein 7 a) X6.8 is C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, phenyl and β beta -4, Xg.7 are as defined above, b) Xe.7 and X1 taken together with the nitrogen atom to which they are attached form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl , c) Χ ^ and Xq.7 together with the added nitrogen atom form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, -N (X6.4) -CO- (X6.9) wherein X6.4 is defined above and X6.9 is a C 1 -C 4 -alkyl group or a phenyl group, a -O-promedicine, wherein the promedication is -PO 2 C 1 -C 4 -CH 2 -CO-NH-CH 2 -SO 2 '. cation4, a group -CO- (CH2) n21 R51, wherein n21 = 1-7, R51 is carboxy ". cation4, -ΝΡ51, R51.2, where R8 and R51.2 are the same or different and represent a hydrogen atom or a C1-C6alkyl group, -N + R51.1 R51.2 R51.3. Hal ', where R51i, R51_2 and R51.3 are the same or different and denote hydrogen atom or C1-C3-alkyl, and wherein Hal is chlorine or bromine, -CO-CH (amino acid residue) -NH2, wherein the amino acid is hydrogen , methyl, isopropyl, isobutyl, hydroxymethylene, -CH (OH) - methyl, benzyl, -CH2- [p-hydroxyphenyl], -CH2- [3-indolyl], -CH2-SS-CH2-CH- (NH2) - COOH, -CH2SH, -CH2CH2-S '-CH3i -CH2-COOH, -ch2-co-nh2, -ch2-ch2-cooh, -ch2-ch2-co-n2, -CH2- [2-histidyl], - (CH 2) 3 NH-C (NH) -NH 2 > - (CH2) 4-NH2i -CH2-CH2-CH (OH) -CH2NH2, - (CH2) 3-NH2i - (CH2) 3-NH-CO-NH2 -CH2CH2-OH, -C0-CH = CH-C0 -0 '. cation, -CO-N * -CH = sCH-N = CH *, where the atoms marked with an asterisk (*) bind to each other to form a ring, -CO-C * [(CH2) n22-NH2j-CH = CH-CH = CH * where n 1 or 2 where the atoms marked with an asterisk (*) bind to each other to form a ring, -CO-C * = CH-CH = C (-NR 52) -CH = CH * where R 52 is hydrogen atom or C 1 -C 3 -alkyl, and where the atoms marked with an asterisk (*) bind to each other to form a ring, 8 LV 10264 -CO- (CH 2) n 2t-C 0-0- [C 6 H 20 O-sugars], ~ C0 0 " 0H (CH2-0_C0 " R53) 2) wherein R53 is the same or different and denotes C1-C4 alkyl, -CO- (CH2) 6-CO-N (CH3) -CH2-CH2-SO3. cation +, -CH 2 O-CO-iCH 2 -NG-NR 5 M R 51.2f where n21, Rs1 and R51.2 are referred to above, -CO-NH-C6H4-R55, where R55 is hydrogen, Cl-CValkylnitrogroup, -NR51.t R51.2, where the meanings of R51i and R51.2 are mentioned above, -ΝΧ *, the promedicine, where ^ the meanings of the medicine are as defined above, except that the promedition cannot be a group -P02-0 ";, n2 = 1-3, X6 may be the same or different, and when n2 = 2 and two X6 groups are in the o / f to one another, they may be connected and form a chain -0-CH2-0-; provided that when n2 = 2 or 3, only one of the substituents Xq may be a promeduct; substitute formula (4) where -NX is a group wherein Xn is hydrogen, phenylsulfone, methylsulfone, -ul-Χ ^ where X1M is C1-C6alkyl trifluoromethyl or phenyl; Q2 is nitrogen if Rt is not methylene, -CX12 = where X12 is -COO-X12.1 (where Χ, ^ is hydrogen or C1-C4-alkyl, -CO-N (X12.2) (X12) .3) where X12.2 and X12_3 are the same or different and represent a hydrogen atom or a C1-C4 alkyl group, or X12.2 and X12 ^ together with the nitrogen atom attached thereto form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl group, 1-piperazinyl or N-morpholinyl, 9 -CO-COO-X12i, wherein X12i are as defined above, C1-C3 alkyl, -CO-phenyl, -CO-X12.1t where X12 has the above meanings, -CO-CO-N (X12.2) (X12.3), where X12.2 and X12.3 are as defined above, - (CH2) n23-OH, where n23 = 1 or 2, a substituent of formula (7) X6 and n2 are as above; a substituent of formula (6) wherein is a single or double bond, -O-CH2-O, -O-CF3, X14 is hydrogen, -O-CH2-COOR14.10, where R14.10 is hydrogen, C4-C4- alkyl, phenyl or benzyl, C1-C6 alkyl, fluoro, chloro, or bromo, -O-SO2-X14t1, wherein -X14.1t is (C1-C4-alkyl, cyano, -CHO, - (CH2) n25 *) OH, where n25 = 1-5, nitro, amino, azide, -NH-benzyl, -NH-CH2-O, -NH-SOgOC1 +, where -CH2-C6 alkyl, C3-Ct- cycloalkyl or phenyl, -NX14_2- (CH2) n3 -N (X14.3) (X14 ^), wherein n3 = 2-5, X14.2, X14.3 and X1 < M is hydrogen, C1-C4 alkyl, or X14.3 and X14.4 together with the nitrogen atom to which they are attached form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, -N (X14.13) (Xl4i4). ), where X14.13 and X14.14 are the same or different and represent a hydrogen atom or a Ct-C5 alkyl group, or X14.13 and X14_14 together with the nitrogen atom attached thereto. u form a heterocycle ring, which may be LV 10264 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, - (CH 2) n 6 -N (X 14.5) (X 14 ^), wherein n 6 = 1-5, X14.2, X14.5 and X14 ^ are the same or different and represent a hydrogen atom or a C 1 -C 6 alkyl group, or X 14.5 and X 14.6 together with the nitrogen atom attached thereto form a heterocycle ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, or N-morpholinyl, -N = C (X14) - N (X14.7) (X14.8), wherein a) X14_7 and X14.8 are C1 -C6-alkyl, C3-C7-cycloalkyl or phenyl and X14-, X6.7 are as defined above, b) X14.7 and X14.8 together with the nitrogen atom attached thereto form a heterocyclic ring which may be 1-pyrrolidinyl- , 1-piperidinyl, 1-piperazinyl or N-morpholinyl, c) X14 and X14.7 together with the added nitrogen atom form a heterocyclic ring, possibly 1-pyrrolidinyl, or 1-piperidinyl, -C0-0-X14. 7 where the meaning of X14.7 is high k, -CO-N (X14.7) (X14.8), where X14.7 and X14.8 have previous meanings. -N (X14.2) -CO-X14.9i wherein X14.2 is as defined above and X14.9 is a hydrogen atom C1-C4 alkyl or phenyl, -N (Xu.2) -promedicine, wherein the promedition is as indicated above, except that it is not -P020, and X14.2 is higher, the meanings n7 = 0-2, X6 and Q are indicated above, the substituent of formula (8) * 22 · 2. Diaryl or diheteroaryl-substituted compounds (III) according to claim 1, wherein R 1 is -CO-. 3. Diaryl or diheteroaryl-substituted compounds (III) according to claim 1, characterized in that Z is a group (Z-11): -Yr (CH2) nirZ2- (CH2) n26-Y2 wherein Y1 is a group -N (Y1.1) -, Z2 is -C (Z2.2) (Z2.3) - wherein Z2.2 and Z2.3 are hydrogen, and Y2 is -N2O- or oxygen. 4. Diaryl or diheteroaryl-substituted compounds (III) according to claim 1, wherein Z is a group (Z-III): (Z-UI) (CH2) f2-N) - wherein n12 = 1 and n13 = 1 or 2 5. Diaryl or diheteroaryl-substituted compounds (III) according to claim 1, wherein R6 is a nitrogen atom. 15 6. Diaryl or diheteroaryl-substituted compounds (III) according to claim 1, wherein R6 and R8 are nitrogen atoms. 7. Diaryl or diheteroaryl-substituted compounds (III) according to claim 1, wherein R8, R9 and R10 are -CH = and R6 is a nitrogen atom. (8) wherein X 21 is hydrogen, O, -O 4 -alkyl, -CO- (C 1 -C 4 -alkyl), benzyl, -CO-phenyl or a promedicine having the meanings given above, Χ 22, Χ 23, and X 24 are the same or different and denotes fluorine, chlorine, bromine, hydroxyl, -O-benzyl, -O-trifluoromethyl, -O-CH2-C00H, O, -O3-alkoxy, C1-C3 alkylthio, -O-OC- X22.11 1 is hydrogen, C 1 -C 4 alkyl or phenyl, nitro, amino, azide, cyano, -NX 22.2 ΟΗ 2) η 9-Ν (Χ 22.3) (X22-4) i where ng = 2-5, X? ?,? 22-3 and X22.4? Hydrogen or 0, -O? -Alkyl and X22.3 and X22.4 together with the nitrogen atom attached thereto form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, -O-O- (CH2) n9-C00H, where n9 has the meanings given above, 39 -O- (CH2) n9-N (X22.3) (Χ22-4). where n9, X22.3 and Χ ^ are as above, - (CH2) n10-N (X22.5) (Χ22-6) where n10 = 1-5, but Χ ^^ η Χ22-6 is the same or different and denotes hydrogen, C 1 -C 4 -alkyl, and wherein X 22.5 and X 22 ^ together with the nitrogen atom to which they are attached form a heterocycle ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, -N (X 22 .7) (X22.8) wherein X 22.7 and X 22 is C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl or phenyl, where any two adjacent groups -0-X 21 1 X 23 or X 24 together can form a methylenedioxy group (-O-CH 2). -0) Ο, and the chemical bond ............ is as defined above; substitute formula (9) 8. Diaryl or diheteroaryl-substituted compounds (III) according to claim 1, wherein R7 is a group -N (R7.5) (R6), wherein one of R7.5 and R7 is hydrogen, and the other R7.5 and R7.6 are C1-C4 alkyl. (8) wherein X 21 is hydrogen, C 1 -C 4 alkyl, -CO- (O 4 -C 4 -alkyl), benzyl, -CO-phenyl, or a promoted drug, the meanings of which are given above, 11 Χ 22 ^ 23, and ^ 24 are the same or different and denotes fluorine, chlorine, bromine, hydroxyl, -O-benzyl, -O-trifluoromethyl, -O-CH2-C00H, C) -Calkoxy, CrC3-alkylthio, -O-CO · Χ22.1 »where - X22 is hydrogen, C1-C4 alkyl or phenyl, nitro, amino, azide, cyano, -NX22-2 " (CH2) n9-N (X22.3) (X22 ^) where π9 = 2-5 , X22.2 »Χ22-3 Χ22-4 are hydrogen, C1-C4-alkyl and X22.3 and Χ ^ together with the nitrogen atom to which they are attached form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, -O-C0- (CH2) n9-COOH, where n9, Χ ^ and Χ & .4 are as indicated above, - (CH2) n9-N (X22.3) (X22.4) ) where n9, X22.3 and Χ ^ where meanings are given above, - (CH2) n10-N (X22.5) (Χ &, β) where n1 0 = 1-5, but X22.5 and X22 > 6 are the same or different and denote hydrogen, O0-4-alkyl and wherein Χ22-5 and Χ22-6 together with the nitrogen atom attached to them form a heterocyclic ring which may be 1-pyrrolidinyl , 1-piperidinyl, 1-piperazinyl or N-morpholinyl, -N (X22-7) (Χ22-8) wherein Χ22-7 and Χ22-8 are C1-C6-alkyl, C3-C7-cycloalkyl or phenyl, and wherein any two adjacent groups -0-X21, X22, X23, and X24 together can form a methylenedioxy group (-O-CH2-0-), Q, and the chemical bond is as defined above; substitute formula (9) wherein X10 is hydrogen, fluoro, chloro or bromo, Q3 is -CH = or Q2, where Q2 is of a higher meaning; 12 LV 10264 substituent of formula (10) (10) * 11 where the meanings of X6i Xn and Q3 are given above, the substituent of formula (11) M 9. Diaryl or diheteroaryl-substituted compounds (III) according to claim 8, characterized in that the alkyl group is ethyl, z-propyl or f-butyl-C (CH3) 3. · _V v * f (10) where the meanings of X € i Xt1 and Q3 are given above, substitute of formula (11) (Π) 40 LV 10264 wherein X 7 is hydrogen, -SO 2 -methyl. -SO 2 -phenyl, -CO-X 7.1f wherein X 7, O, -O 4 -alkyl, or phenyl, X 8 is hydrogen, C 1 -C 6 -alkyl, benzyl, -SO 2 -phenyl, -SO 2 -methyl, - CO-X8, wherein X8 is C, -C4 alkyl, or phenyl, chemical bond ---------- as defined above; substitute formula (15) 10. Diaryl or diheteroaryl-substituted compounds (III) according to claim 1, wherein Ari! / heteroaryA is selected from the group of compounds of formulas (4), (7) - (11), (15) and (21). * 11 (15) where X 1 and Q 3 are of previously defined meanings; substitute formula (16) where X 'and Q3 are of the previously defined meanings; substitute formula (17) 41 (17) * 11 (18) wherein Xt1 and Q3 have the previously defined meanings; substitute formula (18) wherein Xu and Q3 have the above defined meanings; substitute formula (19) wherein Xu Q3 is of a previously defined value; substitute formula (20) * 11 (9) wherein X10 is hydrogen, fluoro, chloro or bromo, Q3 is -CH = or Q2, wherein Q2 is as defined above; substitute formula (10) 11. Diaryl or diheteroaryl-substituted compounds (III) according to claim 1, wherein Ari! / heteroaryl - selected from the group of compounds of formulas (4), (7) and (8). • * 11 (16) 13 where Xn and Q3 have predefined meanings; a substituent of formula (17) Ys wherein Xn and Q3 have the above defined meanings; substituent of formula (18) r I * 11 (17) * 11 (15) wherein X 1 and Q 3 are as defined above; substitute formula (16) (11) h K. UI X 7 is hydrogen, -SO 2 -methyl, -SO 2 -phenyl, -CO-X 7 h wherein X 7 is C 1 -C 4 -alkyl, or phenyl, X 8 is hydrogen, C 1 -C 6 -alkyl, benzyl, -SO 2 -phenyl, - $ O 2 -methyl, -CO 2 -, wherein X 8 · is 0-4 alkyl, or phenyl, a chemical bond as defined above; substitute formula (15) 12. Diaryl or diheteroaryl-substituted compounds (III) according to claim 1, wherein said compounds are in particular 1- [indolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1- [indolyl-2-carbonyl-4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [indolyl-2-carbonyl] -4- [3- (N, N-diethylamino) -2-pyridinyl] piperazine 1- [indol-2-yl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1- [5-fluoroindolyl-2-carbonyl] -4- [3-propylamino-2-pyridinyl] piperazine, 1- [ 5-Chloroindolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1- [5-fluoroindolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine [1- -ethylindolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1- [5-fluoroindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [benzofuroyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 16 LV 10264 1- [indolyl-2-carbonyl] -4- [3-ethylamino-phenyl] piperazine, 1- [ indolyl-2-carbonyl] -4- [3- (cyclopropylmethylamino) -2-pyridinyl] piperazine, 1- [5-fluoroindolyl-2-methyl ] 4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [indolyl-2-carbonyl] -4- [3- (2,2,2-trifluoroethylamino) -2-pyridinyl] piperazine, 1- [5-Fluoroindolyl-2-carbonyl] -4- [3- (1,2,2-trifluoroethylamino) -2-pyridinyl] piperazine, 1- [5-benzyloxyindolyl-2-carbonyl] -4- [3-ethylamino-2- pyridinyl] piperazine, " 1- [5-Benzyloxyindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [indol-2-methyl] -4- [3- (1-methylethylamino] - pyridinylpiperazine, 1- [indolyl-2-carbonyl] -4- [3- (1,1-dimethylethylamino) -2-pyridinyl] piperazine, 1- [5-fluoroindolyl-2-carbonyl] -4- [3- (1 1-Dimethylethylamino) -2-pyridinyl] piperazine, 1- [5-fluoroindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [5-fluoroindolyl-2- Carbonyl] -4- [5- (1-Methyl-ethylamino-pyridin-2-yl-piperazine, 1- [indolyl-2-carbonyl] -4- [4- (methylethylamino) -2-pyridazinyl] piperazine [1- (5-fluoroindolyl-2-carbonyl)] -4- [4- (1-Methylethylamino] -S-pyridazinopiperazine, 1- [5-fluoroindolyl-2-carbonyl] -4- [3- (1,1-dimethylethylamino) -2-pyrazinyl] piperazine, N) N ' -dimethyl-N- (indolyl-2-carbonyl) -N '- [3- (1-methylethylamino) -2-pyridinyl] ethylenediamine, N, N' imethyl-N-Ondolylcarbonyl-N '- ^ - O-Methyl-ethylamino-2-pyridinyl] -1,3-propanediamine, N, N'-dimethyl-N-indolyl-4-carbonyl-N'-i-ylmethylethylamino] -pyridinyl .hexanediamine, 2- {N-methyl-N- [3- (1-methylethylamino) -2-pyridinylethylindole-2-carboxylate, 1- [indolyl-2-carbonyl] - [3-cyclopentylamino-2-pyridinyl] piperazine, 1- [indolyl-2-carbonyl] -4- [3-cyclopentylamino-2-pyrazinyl] piperazine, 2- {2- [N-methyl-N- (indolyl-2-carbonyl) amino] ethoxy} -3- (1- methylethylaminoypyridine, 2- [2- (indolyl-2-carboxy) ethoxy] -3- (1-methylethylamino) pyridine, 1- [5- (ethoxycarbonylmethoxy) indolyl-2-carbonyl] -4- [3- (1-methylethylamino) ) -2-Pyridinyl] piperazine, 1- [5-carbomethoxyindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [bezimidazolyl-2-carbonyl] -4- [ 3-ethyl-2-pyridinyl] piperazine, 1- [5-fluoroindolyl-2-carbonyl] -4- [3-methylamino-2-pyridine] piperazine, 17 1- [indolyl-2-carbonyl] -4- [ 3-methylamino-2-pyridinyl] piperazine, 1- [naphthyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1- [5- (benzyloxycarbonylmethoxy) indolyl-2-carbonyl] -4- [3- (1-Methylethylamino-2-pyridinyl] piperazine, 1- [5- (carboxymethoxy) indolyl-2-carbonyl] -4- [3- ( 1-Methylethylamino) -2-pyridinyl] piperazine, 1- [pyrrolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [pyrrolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1- [6-methoxy-7-methylindolyl-2-carbonyl] -4 - [(1-ethylamino) -2-pyridinyl] piperazine 1- [5,6-dimethoxyindolyl] 2-Carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [3-methylindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [indolyl-2-carbonyl] -4- [2- (1-methylethylamino) -4-fluorophenyl] piperazine, 1 - [indolyl-2-carbonyl] -4- [2- (1-methylethylamino) - 5-Fluorophenyl] piperazine, 1- [indoyl-2-carbonyl] -4- [3- (1-pyrrolidinyl) -2-pyridinyl] piperazine, 1 - [indolyl-2-carbonyl] -4- [3-ethylamino] 2-Pyridinyl] -1,4-diazepine, 1- [5-fluoroindolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] -1,4-diazepine, 1 - [indolyl-2-carbonyl] 4- [3- (1-Methyl-ethylamino) -2-pyridinyl] -1,4-diazepine, 1- {2- [5- (N'N'-dimethylaminomethylene) aminoindolyl] carbonyl} -4- [3- ( 1-Methylethylamino) -2-pyridinyl] piperazine ns, 1- [5- (2'-Aminoacetamido) indole-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [6-methoxyindolyl-2-carbonyl] -4 - [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [4-methoxyindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1 - [5- Methoxyindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine 1- [5,6-methylenedioxyindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2- pyridinyl] piperazine, 1- [5-fluoro-6-methoxyindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [7-bromo-6-methoxyindolyl-2- carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [5-bromoindoyl-2-carbonyl] -4- [3- (1-methylethyl) -2-pyridinyl] piperazine , 18 LV 10264 1- [5-bromo-6-methoxyindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [6- (N, N-dimethylamino) indole] -2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [4-methylindole-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine ns, 1- [indolyl-2-carbonyl] -4- [3- (1-ethylpropylamino) -2-pyridinyl] piperazine, 1- [5-aminoindolyl-2-carbonyl] -4- [3- (1-methylethylamino) ) -2-Pyridinyl] piperazine 1- [5-fluoroindolyl] -carbonyl-1H-yl-dimethylpropylamino) -2-pyridinyl] piperazine, 1- [5-nitroindolyl-2-carbonyl] -4- [3- (trans) 1-Methylethylamino) -2-pyridinyl] piperazine, 1- [5-acetamidoindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [5-methanesulfonamidoindolyl-2-carbonyl] ] 4- [3- (1-Methylethylamino) -2-pyridinyl] piperazine, 1- [5-fluoroindolyl-2-carbonyl] -4- [3- (2-methoxy-1-methylethylamino) -2-pyridinyl] piperazine N, N'-dimethyl-N-1-fluoroindolyl-4-carbonyl-N'-p-ylmethylethylamino] -pyridinyl] ethylenediamine, 1- [7-azaindoyl-2-carbonyl] -4- [3- (1 -methylethylamino) -2-pyridinyl] piperazine, 1- [5-azaindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, N, N '< indolyl-24 < arbonyl) -N43-ethylamino-2-pyridinyl] -1,3-propanediamine, N, N'-dimethyl-N-indolyl-carbonyl] -N'-p-ethyl lamino-pyridyl] -1,6-hexanediamine, 1- [6-fluoromethylamino-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1 - [6-Nitroindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [5-azido-2-indolylcarbonyl] -4- [3- (1-methylethylamino) - 2-pyridinyl] piperazine, 1- [indoyl-2-carbonyl] -4- [3- (2-fluoroethylamino) -2-pyridinyl] piperazine, 1 - [indolyl-2-carbonyl] -4- [3- (1 -methylethylamino) -2-pyrazinyl] -1,4-diazepine, 1- [5-benzyloxyindolyl-2-carbonyl] -4- [4- (1,1-dimethylethylamino) -2-pyridazinyl] piperazine, 1 - [5] -hydroxyindole-2-carbonyl] -4- [4- (1,1-dimethylethylamino) -2-pyridazinyl] piperazine, 1- [benz [g] indolyl-2-carbonyl] -4- [3- (1-methylethylamine) ) -2-pyridinyl] piperazine, 19 1- [benz [e] indolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, N, N'-dimethyl-N- ( indolyl-2-carbonyl) -N '- [3-etnamino-2-pyridinyl] -ethylenediamine N, N'-dimethyl-N- (indolyl-2-carbonyl) -N' - [3- (1-methylethylamino) ' pyridinyl] -1,4-butanediamine, 1- [6 -hydroxymethylindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [6-hydroxymethylindolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1- [6- (N, N'-Dimethylamino) methylindolyl-4- [3- (1-methylethylamino) -2 " pyridinyl] piperazine, 1 - [indolyl-7-carbonyl] -4- [3- (1 - methylethylamino) -2-pyridinyl] piperazine, 1- [indolyl-7-carbonyl] -4- [3- (1-ethylamino) -2-pyridinyl] piperazine, 1 - [indolyl-2-carbonyl] -4- {N Methyl-N- [3- (1-methylethylamino) -2-pyridinyl] · * - amino] piperidine, 1- [6-fluoroindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] ] piperazine, I. 1- [5,6-Dimethoxyindolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine, N, N * -dimethyl-N- (indolyl-2-carbonyl) -N '- [3- (1-Methylethylamino) -2-pyridinyl] -2E-butylenediamine, N, N'-dimethyl-N-indolylcarbonyl] -N'-IS-ylmethylethylamino) -2-pyridinyl] -2Z butylenediamine, & 2, 2, N, N, -tetramethyl-N- (indolyl-2-carbonyl) -N, - [3- (1-methylethylamino) -2-pyridinyl] -1,3-propanediamine, N, N'-dimethyl -N- (indolyl-2-carbonyl) -N '- [3- (1-methylethylamino) -2-pyridinyl] -3-oxa-1,5-pentanediamine, N, N', N '' - trimethyl-N - (indolyl-2-carbonyl) -N '- [3- (1-methylethylamino) -2-pyridinyl] diethylene triamine, 1- [6-cyanoindolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] ] piperazine, 1- [6-pyridinylindole-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [6- (1-pyrrolidinyl) indolyl-2-carbonyl] 4- [3- (1-Methylethylamino) -2-pyridinyl] piperazine, 1- [6- (1-pyrrolidinyl) indole-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1 - [6-Dimethylaminoindolyl-2-carbonyl] -4- [3- (1,1-dimethylethylamino) -2-pyrazinyl] piperazine, 20 L 10264 1- [6-dimethylaminoindolyl-2-carbonyl] -4- [3- ( 1,1-dimethylethylamino) -2-pyridinyl] piperazine, 1- [5-nitroindolyl-2-carbonyl] -4- [3- (1,1-dimethylethylamino) -2-pyridinyl] piperazine, 1- [6-hydroxymethylindolyl] -2-carbonyl] -4- [3- ( 1,1-Dimethylethylamino) -2-pyridinyl] piperazine, 1- [2-N- (N '< limethylaminomethylene) aminoindolyl-2-carbonyl] -4- [3- (1,1-dimethylethylamino) -2] Pyridinyl] piperazine, 1- [6-dimethylaminomethylindolyl-2-carbonyl] -4- [3- (1,1-dimethylethylamino) -2-pyridinyl] piperazine. 13. Diaryl or diheteroaryl-substituted compounds (III) according to claim 12, wherein the compounds are in particular 1- [indolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1- [ indoyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [5-fluoroindolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1 - [5-fluoroindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [5-fluoroindolyl-2-methyl] -4- [3- (1-methylethylamino) - 2-pyridinyl] piperazine, η - [indolyl-2-carbonyl] -4- [3- (1-dimethylethylamino) -2-pyridinyl] piperazine,. 1- [5-fluoroindolyl-2-carbonyl] -4- [3- (1,1-dimethylethylamino) -2-pyridinyl] piperazine, 1- [5-fluoroindolyl-2-carbonyl] -4- [3- ( 1-Methylethylamino) -2-pyrazinyl] piperazine, N, N'-dimethyl-N- (indolyl-2-carbonyl) -N '- (1-methylethylamino) -2-pyridinyl] -1,3-propanediamine, 1- [5-Carboxymethoxyindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [3-methylindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [indolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] -1,4-diazepine, 1- [indolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-Pyridinyl] -1,4-diazepine, 1- [N, N-N'-N'-dimethylaminomethylene] -aminoindolyl] carbonyl] - [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [5- (2'-Aminoacetamido) indolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 21 1- [5,6-methylenedioxyindolyl-2-carbonyl] -4- [3- ( 1-Methylethylamino) -2-pyridinyl] piperazine, 1- [6- (N, N-dimethylamino) indolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1 - [indolyl-2-ka ronyl] -4- [3- (1-ethylpropyl) amino-2-pyridinyl] piperazine, 1- [5-methanesulfonamidoindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine , 1- [5-fluoroindolyl-2-carbonyl] -4- [3- (2-methoxy-1-methylethylamino) -2-pyridinyl] piperazine, 1- [6-fluoroindolyl-2-carbonyl] -4- [3] - (1-Methylethylamino) -2-pyrazinyl] piperazine. 14. An anti-AIDS piperazine (IV), characterized in that the compound is selected from the group consisting of 1- [4-methoxy-3,5-dimethylbenzoyl] -4- [3-ethylamino-2-pyridinyl] piperazine. [4-Methoxy-3,5-dimethylbenzyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1- [4-hydroxy-3,5-dimethylbenzyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1- [4-methoxy-3,5-dimethylbenzyl] -4- [3-propylamino-2-pyridinyl] piperazine, 1- [4-methoxybenzyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1- [5-methoxyindolyl-2-carbonyl] -4- [2-ethoxyphenyl] piperazine, '· " 1- [5-Methoxyindolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1- [5-methoxyindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2- pyridinyl] piperazine, 1- [5-methoxyindolyl-2-carbonyl] -4- [2- (ethylamino) phenyl] piperazine, 1- [5-hydroxyindolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] ] piperazine, 1- [5-hydroxyindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [5-methoxy-4,6,7-trimethylindolyl-2-carbonyl] - 4- [3-ethylamino-2-pyridinyl] piperazine, 1- [5-methoxyindolyl-2-carbonyl] -4- [1,1 - (dimethylethylamino) -2-pyridinyl] piperazine, 1- [5-methoxyindolyl-2-carbonyl] -4 [3-methylamino-2-pyridinyl] piperazine, 1- [3,5-dimethyl-4-methoxybenzoyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [3,5-dimethyl-4- methoxybenzoyl] -4- [3 (1-ethylethylamino) -2-pyridinyl] piperazine, 1- [5-methoxyindolyl-2-methyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1 - [5] -fluorindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] -1,4-diazepine, 22 LV 10264 N, N-dimethyl-N- [5-methoxyindolyl] 2-Carbonyl] -N '- [3- (1-methylethylamino) -2-pyridinyl] ethylenediamine, 1- [4-methoxy-3,4-dimethylbenzyl] -4- [3- (2-propenylamino) -2-pyridinyl] ] piperazine, N, N '-dimethyl-N- [5-methoxyindolyl-2-carbonyl] -N' - [3- (1-methylethylamino) -2-pyridinyl] -2E-butylenediamine, N, N'-dimethynyl-N- CS-Methoxyindolylcarbonyl-N'-fS-yl-methylethylamino) -2-pyridinyl] -2Z-butylenediamine, 1- [5-methoxyindolyl-2-carbonyl] -4- [3-methylamino) -2-pyridinyl] piperazine, 1- [5-Methoxyindolyl-2-carbonyl] -4- [3-propylamino-2-pyridinyl] piperazine, 1- [5-methoxyindolyl-2-carbonyl] -4- [3-cyclopropylmethylamino-2-pyridinyl] piperazine 1- [5-methoxyindolyl-2-carbonyl] -4- [3- (1,1-dimethylethylamino] -pyridinyl] piperazine and their enantiomers, pharmaceutically acceptable salts, hydrates and solvates. 15. Anti-AIDS piperazine (IV) according to claim 14, wherein the compound is selected from the group consisting of 1- [5-methoxyindolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine, 1- [5-methoxyindolyl-2-carbonyl] -4- [3- (1-methylethylamino) -2-pyridinyl] piperazine, 1- [5-hydroxy-indolyl-2-carbonyl-4- [3- (1- methylethylamino) -2-pyridinylpiperazine, 1- [5-methoxyindolyl-2-carbonyl] -4- [3- (1,1-dimethylethylamino) -2-pyridinyl] piperazine, 1- [5-methoxyindolyl-2-carbonyl] - 4- [3-Methylethylamino-2-pyridinyl] piperazine. I » 16. Anti-AIDS piperazine (IV) according to claim 14, wherein the compound, in particular 1- [5-methoxyindolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine. 17. Indole of formula (V) wherein R1A is -CH2-, -CO-, -CO-CH2-, -SO2- or -CH = CH-CO-; Z is one of the following groups; in which: 23 (I) R2 is oxygen or R2.1 and R2.2l of which one is hydrogen, and the other of R2 and R2 are hydrogen or methyl, R3 is oxygen or R1 and R4 are hydrogen. and the other of R 1 and R 4 is hydrogen or methyl, R 4 is R 4t and R 1 is R 5, and R 5 is R 5, and one of R 1 and R 6 is also R 1 and R 5. .2 is hydrogen and the other of R4-1 and R4.2 as well as one of R5.1 and R5.2 is hydrogen or methyl; (II) R4 is R4.3 and R4.4, and R5 is R5.3 and R5.4, where one of R4.3 and R4.4 and one of R5.3 and R5.4 together form a methylene group; but the other of R4.3, R4w, and R5.3, R8, are hydrogen; R2 and R3 are hydrogen; (III) R2 is R2.5: R2.6 and R5 are R5.5: R5.6, where one of R2.5 and R2.6 and one of R5.5I R5.6 together forms an ethylene group, while the other of these groups are hydrogen; R3 and R4 are hydrogen; (IV) R3 is R3.5, R3.6 and R4 are R4.5, R4 <, wherein one of R3.5 and R6 and one of R6 and R4.6 together form an ethylene group, and the others of this group are hydrogen; Rz and R5 are hydrogen; wherein nn = 1-5, n26 = 1-5, Y1 oxygen, sulfur, or -ΝίΥ ^) -, where ΥΜ is C1-C4-alkyl -C (Yl ^) (Y14) - wherein Y1.2 and Y ^ is the same or different and represents a hydrogen atom or a C 1 -C 4 alkyl group; 24 LV 10264 Y2 is an oxygen or sulfur atom, the group -N ^ --O-, wherein Y2i is C1-C4 alkyl; " C (Y2.2) (Y2-3) " · wherein Y2.2 and Y2.3 are the same or different and represent a hydrogen atom or a C 1 -C 4 alkyl group; Z2 chemical bond, oxygen or sulfur atom, -NiZ1-), wherein Z2- is hydrogen or C1-C4 alkyl, -C1C-; -C (Z2.2) {Z2 ^) - wherein Z2.2 and Z2.3 are the same or different and represent a hydrogen atom or a C1-C4 alkyl group; cis · and trans · -C (Z2.2) = C (Z2_3) - wherein Z2.2 and Z1 are the same or different and represent a hydrogen atom or a C1-C4 alkyl group; provided that 1) when Y 1 is an oxygen or sulfur atom or a group -N (Yl ii) -, nt 1 = 1 only when Z 2 is a chemical bond or groups -C = C-; -C (Z2.2) (Z2.3) -, • C (Z2.2) = C (Z2.3) -; and 2) when Y 2 is an oxygen or sulfur atom or a group -Ι ^ Υ ^) -, n 26 = 1 only when Z 2 is a chemical bond or -OC-; -C (Z2.2) (Z2.3) -, • C (Z2.2) = C (Z2.3) -; —CCH2 > iii2 (Ζ-ΠΙ) where n12 = 1 or 2 and n13 = 1 or 2; (Z-IV) wherein n12 and n13 have the above meanings; (Z-V) 25 wherein Y 3 is -ΝίΥ ^,) - wherein Υ is 0, -O 4 -alkyl, and n 12 and n 13 are as defined above; R6 is nitrogen, -CH = or -N (O) =; R7A is a group SR7A_ where R7A is Ct-C6-alkyl, -O-R7A.2, where R7A.2 is C1-C6-alkyl, -C (R7A.15) (R7A-16) - ( R7A-17). wherein R7A.15 and R7A.16 are the same or different and represent a hydrogen atom or a C1-C3 alkyl group; R7A-17k 02-C5-alkenyl containing 1 or 2 double bonds, or C2-C5-alkenyl with one triple bond, -C-OR7A.11t where R6 is hydrogen, C1-C8-alkyl , C2-C6-alkenyl having 1 or 2 double bonds, C2-C6-alkynyl with one triple bond, benzyl, phenyl, which may be optionally substituted with 1-3 of the following groups: trifluoromethyl, O, O4-alkyl, hydroxy, C 1 -C 3 -alkylthio, -O-C 0 R 7A.12 (wherein R 7A.12 is C 1 -C 6 -alkyl or phenyl) fluoro, chloro or bromo, trifluoroacetyl, nitro, N • (R 7A-i 3) (R 7a-h) »wherein R 7A. 14 is the same or different and represents a hydrogen atom or a 0, -O3-alkyl group, or R7A.13 and R7A.14 together with the added nitrogen atom form a heterocycle ring which may be% 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl; -COOR7A.11f where R ^. ,, meanings are set higher; -CO-N (R7A.3) (R7A.4) where R7A.3 and R7Aj are the same or different and represent a hydrogen atom or a C1-C6 alkyl group, • N (R7a-5) (R7A-6). wherein R 7A 5 is C 1 -C 6 -alkyl or a group -C (R 7A-15) (R 7a-i 6) - (R 7A-17). wherein R7A.15, R7A.16 and wherein R7Ai7 are as defined above, and R7A.17 may be -CH2-CH2OH, -CH2-CH2-CH2OH, -CH- (CH3) -CH2-0-CH3, -CH (CH3) -CH2OH, CH2OF3i -CH2-cyclopropyl, -CH2-CH2F, -CH2-CH2CsN, = C * H- (CH2) n14-C * H2- wherein n14 = 1-5, but carbon atoms an asterisk (*) connected to each other to form a ring; - (CH2-) nt-N (R7A_7) (R7a.e) where n, = 2 or 3, and R7A.7 and R7A.8 are the same or different and represent hydrogen or C1-C4 alkyl, or R7A7 and R7A.8 together with the nitrogen atom to which they are attached form a heterocyclic ring, which may be 26 LV 10264 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl or 1-aziridinyl; R7A-6 is hydrogen, C1-C6-alkyl or -C (R7A1i) (R7A-16) - (R7A-i7) wherein R7A-15 > R7A-i6 and R7A.17 have the above meanings and R7. 17 may also include -CH 2 CH 2 OH, -CH 2 CH 2 CH 2 -OH, -ch 2 CF 3i -ch 2 ch 2f, -ch 2 ch 2c = n, or R 7A.5 and R 7A 6 together with the added nitrogen atom form a heterocycle ring which may be 1- pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl or 1-aziridinyl; - (CH2) n4-N (R7A.9) (R7A-io) wherein n4 = 1 or 2 and R7A.9, R7A.10 are the same or different and represent hydrogen or C1-C4alkyl or R7A. 9 and R7A.10 together with the added nitrogen atom form a heterocycle ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl; R8 is a nitrogen atom, -CR8.sup.1 = where R8 is hydrogen, fluorine, chlorine, bromine, trifluoromethyl, nitro, trifluoroacetyl, C1-C6 alkyl, C1-C3 alkylthio, hydroxy, -OR8.2, wherein R8.2 is C1-C6-alkyl, phenyl, -COR8.3, wherein R8.3 is C1-C6-alkyl or phenyl, -NHR8-, wherein R8-4 is C1-C6-alkyl, -C (R8.7) (R8.8) - (R8.9) wherein R8.7 and R8.8 are the same or different and represent hydrogen, C1-C4 alkyl, and R8.9 is a C2-C5 alkenyl group with 1 or 2 double bonds or C2-C5 alkynyl with one triple bond, -NR8.5-CO-R8.6, wherein R8.5 is hydrogen or C1-C6-alkyl or C1-C6-alkoxy; R 9 is a nitrogen atom or a group -CR 9 = where R 9 is hydrogen, fluorine, chlorine, bromine, nitro, trifluoroacetyl, C 1 -C 6 alkyl, C 1 -C 8 alkylthio, hydroxy, -OR 9.2, where R 9. 2 is C 1 -C 6 -alkyl, phenyl, -COR 9.3, wherein R 9.3 is C 1 -C 6 -alkyl or phenyl (provided that R 9.3 is not alkyl, when R 7 is -OR 7.2), -N (R 9). 4) (R9.5), where R9.4 and R9.5 are the same or different and represent a hydrogen atom or a C 1 -C 6 alkyl group, -C (R 9.8) (R 9.9) - (R 9a) » where R9.8 and R9.9 are the same or different and represent hydrogen or C1-C3 alkyl, and R910 is a C2-C5 alkenyl group with 1 or 2 double bonds or a C2-C5 alkynyl group with one triple bond, R9.4 and R 9.5 together with the nitrogen atom to which they are attached form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, -NR 9.6-CO-R 9.7, wherein R g is hydrogen, C 1 -C 6 -alkyl and R 9.7 are hydrogen, C 1 -C 6 -alkyl or C 1 -C 3 -alkoxy; R 10 is a nitrogen atom or a group -CR, ^ where R 1 is hydrogen, fluorine, chlorine, bromine, trifluoromethyl, nitro, trifluoroacetyl, C 1 -C 6 alkyl, C 1 -C 6 alkylthio, hydroxy, -OR 10.2, where R 10. 2 is C 1 -C 6 alkyl or phenyl, -COR 10.3, wherein R 10.3 is C 1 -C 8 alkyl or phenyl, -N (R 10.4) (R 10-5), wherein R 1 (M and R 10 = 5 are the same or and represents hydrogen, C 1 -C 8 -alkyl, -C (Rio-e) (R 10-9) - (R 10-10) where R 10-8 and R 10-9 are the same or different and represent a hydrogen atom or a C t C3-alkyl, and R10-i is a C2-C5-alkenyl group having 1 or 2 double bonds or a C2-C5-alkynyl group with one triple bond, -NR10.6-CO-R10.7, wherein R10.6 is hydrogen or \ t C 1 -C 8 -alkyl and R 10.7 are hydrogen, C 1 -C 6 -alkyl or C 3 -C 3 -alkoxy, provided that no more than two of the radicals R 6i R 8i R 9 and R 10 are nitrogen; a simple or double chemical bond; Q1 is a -NXir group in which Xt1 is a hydrogen atom s, phenylsulfone, methylsulfone, -ΟΟ-C 1-4, a group wherein R 4 is C 1 -C 4 alkyl, trifluoromethyl or phenyl; X 17, X 18 and X 19 are hydrogen or methyl; X 20 is hydrogen, C 1 -C 4 alkyl, -CO- (C 1 -C 4 alkyl), benzyl, -CO-phenyl, or a promedication, wherein the promedic is -PO 2 ion, -C0-CH 2 -C 0 -CH 2 -S0 20 '' . cation, group -CO- (CH2) n21 R51, wherein n21 = 1-7, R51 is carboxy. cation, -NRs., R51.2, where Rs,., and R51.2 are the same or different and represent hydrogen atom or CVCValkyl, -N * R51.i R51.2 R51.3.Har where R51-1 . R5t-2 and R51.3 are the same or different and represent a hydrogen atom or a C 1 -C 7 alkyl group and wherein Hal is a chlorine or bromine, -CO-CH (amino acid residue) -NH 2, wherein the amino acid residue is hydrogen, methyl, isopropyl , isobutyl, hydroxymethylene, 28 LV 10264 -CH (OH) - methyl, benzyl, -CH2- [p-hydroxyphenyl], -CH2- [3-indolyl], - CH2-SS-CH2CH (NH2) -COOH, -CH2SH , -CH2 CH2 -S-CH3i -ch2-cooh, -ch2-conh2 > -ch2- ch2-cooh, -ch2-ch2-co-nh2 < -CH2- [2-histidyl], - (CH2) 3-NH-C (NH) -NH2, - (CH2) 4-NH2i -CH2CH2-CH (OH) CH2NH2t - (CH2) 3-NH2i - (CH2) 3-NHCONH2j -CH2CH2-OH, -C0-CH = CH-C0-0 ·. cation, -CO-N * -CH = CH-N = C * H, where atoms marked with an asterisk (*) bind to each other to form a ring, -CO-C * = C [(CH2) n22-NH2] - CH2 = CH-CH = C * H where n22 = 1 or 2 and where the atoms marked with an asterisk (*) bind to each other to form a ring, -CO-C * = CH-CH = C (NR52) -CH = C * H, where R52 is hydrogen or C1-C3 alkyl and where the atoms marked with an asterisk (*) bind to each other to form a ring, -CO- (CH2) n21-C00- [C6H1206-sugars], -CO-O - CH (CH2O-C0-R53) 2, wherein R53 is the same or different and denotes C1-C6-alkyl, -CO- (CH2) 6-CO-N (CH3) -CH2CH2-SO3 ·. cation, -CH2-0-0C- (CH2) n21-NR51.1 R51.2, where n21, R8 and R51.2 are referred to above, -CO-NH-C6H4-R55, where R55 is hydrogen, CVCValkyl , nitrogroup, NR51-1 R51-2. where the meanings of R 4 and R 51.2 are mentioned above, provided that R 1A is not methylene when the radicals R 17, R 18 and R 19 are methyl; as well as the enantiomers, pharmaceutically acceptable salts, hydrates and solvates of said compounds for use in the manufacture of a medicament for treating immunodeficiency virus (HIV) infected patients. Use of an indole of formula (V) for the preparation of a medicament according to claim 1. For the treatment of 17 patients infected with immunodeficiency virus (HIV) who have a positive reaction to the (HIV) antigen but not to the symptoms of AIDS. 29 (18) where Xn and Q3 have the previously defined meanings; substitute formula (19) wherein Xu and Q3 have the above defined meanings; substitute formula (20) wherein X 1 and Q 3 are of previously defined meanings; 14 (20) (21) LV 10264 a substituent of formula (21) W '7 where Ql, X6 and n7 are definitely higher; with the proviso that one of the substituents R7.5 or R7.6 must be a hydrogen atom when R6 is not a nitrogen atom as well as the enantiomers, pharmaceutically acceptable salts, hydrates and solvates of said compounds. Use of an indole of formula (V) for the preparation of a medicament according to claim 17 for the treatment of patients infected with human immunodeficiency virus (HIV) who have symptoms of the disease but are not developing AIDS diseases. (20) where X1t Q3 has a predetermined meaning; substitute formula (21) 42 (21) LV 10264 wherein Q1 (X6 and n7 are defined above; as well as the enantiomers, pharmaceutically acceptable salts, hydrates and solvates of said compounds, for use in the manufacture of a medicament for treating human immunodeficiency virus (HIV) infected patients. Use of an indole of formula (V) for the preparation of a medicament according to claim 1. For the treatment of 17 patients infected with human immunodeficiency virus (HIV) who have developed AIDS disease. Use of an indole of formula (V) for the preparation of a medicament according to claim 1. For the treatment of 17 patients infected with human immunodeficiency virus (HIV), the product is administered orally. Use of an indole of formula (V) for the preparation of a medicament for treating a patient infected with a human immunodeficiency virus (HIV) according to claim 1. 17, wherein about 0.10 to 500 mg / kg of the preparation is administered daily. Use of an indole of formula (V) for the preparation of a medicament according to claim 1. For the treatment of 17 patients infected with human immunodeficiency virus HIV, the product is given in combination with an OCT or other antiviral agent. Use of an indole of formula (V) for the preparation of a medicament according to claim 1. 17 for the treatment of human immunodeficiency virus (HIV) infected patients, wherein the preparation is 1- [5-methoxyindolyl-2-carbonyl] -4- [3-ethylamino-2-pyridinyl] piperazine. A preparation is 1- [indolyl-2-carbonyl] -4- [3-nitro-2-pyridinyl] piperazine (P10); 1- [5-fluoroindolyl-2-carbonyl] -4- [3-nitro-2-pyridinyl] piperazine (P17); 1- [indolyl-2-carbonyl] -4- [3-amino-2-pyridinyl] piperazine (P22); N, N '-dimethyl-N- (indolyl-2-carbonyl) -N' - [3-nitro-2-pyridinyl] ethylenediamine (P35); 2- {N-methyl-N- [3-nitro-2-pyridinyl] amino} ethylindole-2-carboxylate (P37); 304 102- 1- [5-Fluoroindolyl-2-carbonyl] -4- [3-amino-2-pyridinyl] piperazine (P129); 26. Anti-AIDS amine of formula (X) r7B (X) [Aryl / Heteroaryl] -R1B- wherein R1B is -CH2, -CO-; Z is one of the following groups: M% h (Z-1) wherein: (1) R 2 is oxygen or R 2, and R 2, 2 is hydrogen, and the other of R 2 and R 2 is hydrogen or methyl; R3 is oxygen or R3, and R3.2 of which one is hydrogen, and the other of R3 and R3.2 is hydrogen or methyl, R4 is R6 and R6 is R5 and R5 is R5 and R5 is R wherein one of R 4 · and R 4, as well as one of R 4 and R 5.2 is hydrogen, the other of R 4 and R 4, as well as one of R m and R 5.2 is hydrogen or methyl; (II) R 4 is R 4 and R 4 4 f and R 5 is R 5.3 and R 4 is where one of R 4.3 and R 4.4 and one of R 5-3 and R 4 together form a methylene group and the other of R 4 are , R4.4) and Rg.3, R6, are hydrogen; R2 and R3 are hydrogen; (III) R2 is R2.5: R2.6 and R5 is R5.5, R6, where one of R2.5 and R6 and one of R5-5 and R5.6 together form an ethylene group, and the other of this group is hydrogen. ; R3 and R4 are hydrogen; 31 (IV) R3 is Ra.5, R4 and R4 are R4.5, R4.6 > wherein one of R3.5 and R6 and R4.5 and R4.6 together form an ethylene group and the other of this group is hydrogen; R2 and R5 are hydrogen; (Z-11) -Y 1 ~ (ΟΗ2) Π11-Ζ2- (ΟΗ2) Π26 · Υ2 " wherein ηιι = 1 · 5, η26 = 1 · 5, Yi oxygen atom, sulfur atom or group where C 1 -C 4 -alkyl -C (Y1.2) (Y1.3) -I wherein Yu2 and Y1 are the same or different and denotes a hydrogen atom or a C 1 -C 4 alkyl group; Y2 is an oxygen or sulfur atom, the group -ΝΚΥ ^) - wherein Y2t is C1-C4-alkyl; -C (Y2.2) (Y2.3) -f wherein Y2.2 and Y2.3 are the same or different and represent a hydrogen atom or a C1-C4 alkyl group; A Z2 chemical bond, an oxygen or sulfur atom, a group -N (Z2.) - wherein Z2r is hydrogen or C1-C4 alkyl, -C1C-; -C (Z2.2) (Z2.3) -, where Z2.2 and Z2.3 are the same or different and represent hydrogen atom or C 1 -C 4 (a group; c / s- and trans- -C (Z 2.2) ) = C (Z2.3) - where Z2.2 and Z2.3 are the same or different and denotes hydrogen or C 1 -C 4 alkyl, provided that 1) when Υ 1 is an oxygen or sulfur atom or a group - ΝίΥ ^) -, n1t = 1 only if Z2 is a chemical bond or a group -CsC-; -C (Z2_2) (Z2.3) -, -C (Z2.2) = C (Z2_3) -; and 2) when Y 2 is an oxygen or sulfur atom or a group -ΝίΥ ^) -, n 26 = 1 only when Z 2 is a chemical bond or a group -OC-; -C (Z2.2) (Z2.3) -, ^ 12 (z-m) wherein n12 = 1 or 2 and n13 = 1 or 2; 32 LV 10264 - C (Z-IV) wherein n12 and n13 have the meanings given above; (Z-V) wherein Y 3 is -ΝίΝ ^) - wherein kurā 3 > 1 is C 1 -C 4 alkyl, and n 12 and n 13 are as defined above; R6 is nitrogen, -CH =; R7B is a group -CO-R7EM1, where R 1 is hydrogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl with 1 or 2 double bonds, or C 2 -C 5 -alkynyl with one triple bond, benzyl, phenyl which may be optionally substituted with 1-3 following groups: trifluoromethyl, C 1 -C 4 -alkyl, hydroxy, C 1 -C 3 -alkylthio, -O-C 0 -R 7B.12 (where R 7B.12 is C 1-6 -alkyl or phenyl) fluoro, chloro or bromo, trifluoroacetyl, nitro group, N (R7B_13) (R7B.U), wherein R7B.13 and R7B.14 are the same or different and denote hydrogen or C1-C4 alkyl, or R7B.13 and R7B.14 together with the added nitrogen an atom formed by a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl; - where R7B1 is C1-C6 alkyl, -OR7B.2, where R7B2 is (C1-C6 alkyl, -C (R7B.15) (R7B-16) - (R7B-17). R7B, 16 are the same or different and represent a hydrogen atom or a C 1-4 alkyl group but R 7b -17 'r C 2 -C 5 alkenyl containing 1 or 2 double bonds or also a C 2 -C 5 alkenyl group with one triple bond, R 8, R 9 and R10 nitrogen or -CH = provided that no more than two of the radicals R6, R8, R8 and R10 are nitrogen: Aryl / heteroaryl is a substituent selected from the group consisting of: (1) 33 ( 1) (1) wherein X 1 and X 2 are hydrogen, C 1 -C 6 alkyl, or n-alkyl, h X 4 and X 5 are the same or different and represent hydrogen, C 1 -C 4 alkyl, - (CH 2) n 5 'N (X 4.1) (X 4.2). wherein n5 = 2 or 3 and wherein X4l and X4.2 are the same or different and represent a hydrogen atom or a C1-C4 alkyl group, or X4l and X4.2 together with the nitrogen atom attached thereto form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl; X4 and X5 may be taken together with them to form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl; E E X and X 2 are as defined above, provided that X 4 and X 5 are both not simultaneously hydrogen; a substituent of formula (3) (3) wherein X6 is hydrogen, fluorine, chlorine, bromine, Cl-CValkyl, hydroxyl, methoxyphenyl, trifluoromethoxy, -ΟΟΗ ^ ^ 4, wherein Xe_14 is hydrogen, (C1-C6 alkyl) , phenyl, benzyl, -CHO, C 1-3 -alkoxy or C 1 -C 6 -alkylthio, -ΟΟΟΧβ. where kur 6 is hydrogen, C 1 -C 4 -alkyl or phenyl-, -SO 2 X 6.12 wherein X 6. 12 is C 1 -C 4 alkyl, 34 LV 10264 -COO-X6.13, where ββ13 is hydrogen, C 1 -C 4 -alkyl phenyl group or benzyl; cyano, nitro, N 3, -N (Xe 10) (^ 6) -11) where X6.10 X6n is the same or different and represents a hydrogen atom or a C1-C8 alkyl group, or Χβ.10 and Χβ. ^ Together with the nitrogen atom to which they are attached form a heterocyclic ring which may be 1- pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl or 1-aziridinyl, -N (X6.2) (CH2) n3-N (X6.3) (X6.4) wherein n3 = 2-5, X6 .2 Χβ.3ι and Χβ ^ are hydrogen or C 1 -C 6 alkyl, or ββ3 and X6, together with the nitrogen atom to which they are attached, form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl, or 1-aziridinyl, -OCO- (CH2) n3-COOH, where n3 is determined higher, -0- (CH2) n3-N (X6.3) (X6.4), where n3, X6.3i and Χβ_4 are of the above-defined meanings, " (CH2) n24-OH, where n24 = 1-5, - (CH2) n6-N (X6.5) (X6.6), where n6 = 1-5, and X6.5 and X6.6 are the same or different and represent a hydrogen atom or a C 1 -C 4 an alkyl group, or also X6.5 and X6.6 together with the nitrogen atom to which they are attached form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl, -NH-SO2-Xe.7t where X6. 7-C 1 -C 6 -alkyl, O-CV-cycloalkyl, phenyl or benzyl, -N = C (X 6 - 4) -N (X 6 -7) (X 6 -8) where a) Χβ, β is C 1 -C 4 -alkyl, C 3 -C 7 -cycloalkyl, phenyl and Χβ ^, X6.7 are as defined above, b) Xfi.7 and X < 5 ^ together with the nitrogen atom attached thereto forms a heterocyclic ring, which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, c) X6-4 and Χβ_7 together with the added nitrogen atom form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, -Ν (Χ ^) - 00- (Χβ.9), where Χβ-Λ is higher and Χδ-9 is hydrogen Coms-Cil alkyl or phenyl, -O-promedicine, where the promedication is -P020 \ t -CH2-C0-NH-CH2-SO2, the group -CO- (CH2) n21 R51t wherein n21 = 1-7, R51 is carboxy. cation, -NR 8 - R 51.2, where R 5, R 4 and R 51 are the same or different and represent a hydrogen atom or a C 1 -C 3 alkyl group, -N + R 51.1 R 51.2 R 51.3 Ha! R51.2 and R51.3 are the same or different and represent a hydrogen atom or a C 1-4 alkyl group and wherein Hal- is a chlorine or bromine, -CO-CH (amino acid residue) -NH 2, wherein the amino acid residue is hydrogen, methyl, isopropyl , isobutigroup, hydroxymethylene, -CH (OH) - methyl, benzyl, -CH2- [p-hydroxyphenyl], -CH3- [3-indolyl], -CH2-SS-CH2-CH - (NH2) -COOH, -CH2SH , -CH2CH2-S-CH3t -CH2-COOH, -CH2-CONH2i -CH2-CH2-COOH, -ch2-ch2-co-nh2, -CH2- [2-histidyl], - (CH2) 3-NH-C (= NH) -NH2i - (CH2) 4-NH2, -CH2CH2-CH (OH) -CH2NH2i - (CH2) 3-NH2, - (CH2) 3NH-CO-NH2, -CH2CH2-OH, -C0-CH = CH-C0-0 ion, -CO-N * -CH = CH-N = CH *, where atoms marked with an asterisk (*) bind to each other to form a ring, -CO-C * -C [(CH2) n22-NHJ-CH = CH-CH = CH *. where n ^ 1 or 2, where the atoms marked with an asterisk (*) bind to each other to form a ring, -CO-C * = CH-CH = C (-NR52) -CH = CH *, where R52 is hydrogen or CrC3 -alkyl and where the atoms marked with an asterisk (*) bind to each other to form a ring, -CO- (CH2) n21-C0-0- [C6H1206-sugars], ~ C0_ * CH (CH2 “0 * C0 ~ R53) 2 wherein R 1 tr is the same or different and represents C 1 -C 8 alkyl, -CO- (CH 2) 6 -CO-N (CH 3) -CH 2 CH 2 -SO 3 '. cation, -CH2-OOC- (CH2) n21-NR51.1 R51.2, where n21, R51-i and R51.2 are referred to above, -CO-NH-C6H4-R55, where R55 is hydrogen, ( VC3-alkyl, nitrogroup, NR51.1 RS1.2, where the meanings of Rsm and R51.2 are mentioned above, -ΝΧ ^ promedicine, where the meanings of the prescription drug are as defined above, except that the promedication cannot be group -P020 ', n2 = 1-3, X6 may be the same or different when n2 = 2 and the two X6 groups are orphaned to each other, they may be connected and form a chain 36 LV 10264 -O-CH2-O-; if n2 = 2 or 3, only one of the substituents X6 may be a prodrug; wherein Q 1 is a -NKn- group in which Xn is a hydrogen atom, a phenylsulfone group, a methylsulfoxyl group, -ΟΟ-Χ ^ ^ where X 1 M is C 1 -C 4 alkyl, trifluoromethyl or phenyl; Q2 is nitrogen if there is no methylene group, -CX12 =, where X12 is -COO-? ^, Wherein X12 is hydrogen or C1-C4 alkyl, -CO-N (X12.2) (X12.3) ), where X12.2 and X12.3 are the same or different and represent a hydrogen atom or a C1-C4 alkyl group, or X12-2 and X12.3 together with the nitrogen atom attached thereto form a heterocyclic ring which may be 1-pyrrolidinyl, 1 Piperidinyl, 1-piperazinyl, or N-morpholinyl, -ΟΟ-ΟΟΟ-Χ ^, wherein X12 is as defined above, C 1 -C 6 -alkyl, -CO-phenyl, -CO-X 12.1f wherein X 12 i is the above-mentioned meanings, -CO-CO-N (X12.2) (X12.3), where X12_2 and X12.3 are as defined above, - (CH2) n23-OH, wherein n23 = 1 or 2, X6 and n2 are as mentioned above; substitute formula (6) 37 substitutes for formula (7) where there is a single or double bond, X14 is hydrogen, -O-benzyl, -O-trifluoromethyl, -O-CH2-COOR14.10, where R14.10 is hydrogen, (C1-C4 alkyl, phenyl or benzyl, Ct- C6-alkyl, fluoro, chloro, or bromo, -O-SO2-Xt4-n, wherein -X14 is C1-C4-alkyl, cyano, -CHO, - (CH2) n25-OH, where n25 = 1- 5, nitro, amino, azide, -NH-benzyl, -NH-SO2-X14.1f where -Χ14, is C1-C6 alkyl, C3-C7cycloalkyl or phenyl, -NX14.2 (CH2) n3 -N (X14.3) (X14.4), where n3 = 2-5, X14.2, X14.3 and X14.4 are hydrogen, or C1-C4 alkyl, or X14.3 and X14.4 together with them the added nitrogen atom forms a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, -N (Xi4_i3) (X14- | 4) wherein X14.13 and X14.14 are the same or denotes a hydrogen atom or a C 1 -C 8 -alkyl group, or Χ 14 Ί 3 and X 14.14 together with the nitrogen atom to which they are attached rocikia ring, which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, - (CH2) n6 -N (X14.5) (Χ ·) 4 ^) ι where n3-1-5, Χ14 .5 and X4-4 are the same or different and represent a hydrogen atom or a C1-C4 alkyl group, or X14.5 and X14-e together with the nitrogen atom to which they are attached form a heterocyclic ring which may be 1-pyrrolidinyl-, 1-piperidinyl- , 1-piperazinyl or N-morpholinyl, -N = C (X144) -N (X14.7) (X14.8), wherein a) X14.7 and X14.8 are C1-C8-alkyl, C3-C7 -cycloalkyl or phenyl and X144 are as defined above, 38 LV 10264 b) X14_7 and X14 "8 together with the nitrogen atom attached thereto form a heterocyclic ring which may be 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, c) X14.4 and X14.7 together with the added nitrogen atom form a heterocyclic ring, which may be 1-pyrrolidinyl, or 1-piperidinyl, -COO-X14.7 wherein X14.7 is as defined above, -CO-N (Xu) .7 ) (Xu ^), where X14.7 and X14.8 have previous meanings. -N (X, 4.2) -CO-X14.9, wherein X14.2 is as defined above and X14.9 is a hydrogen atom, C 1 -C 6 alkylalkyl or phenyl, -H {Xu.2) -promedicine wherein the promedication is as defined above except that it is not -P02-0, and X14_2 have the meanings given above, n7 = 0-2, X6 and Q, the meaning indicated above is a substituent of formula (8) 27. The use of an anti-AIDS amine of formula (X) for the preparation of a medicament according to claim 1. For the treatment of 26 patients infected with immunodeficiency virus (HIV), who: 1) have no symptoms of AIDS but have a positive response to the HIV antigen, 2) have symptoms of the disease, but have not developed AIDS, 3) have developed AIDS disease. 28. The use of an anti-AIDS amine of formula (X) for the preparation of a medicament according to claim 2. For the treatment of 26 patients infected with immunodeficiency virus (HIV), the product is administered orally at a daily dose of about 0.10 to 500 mg / kg of the preparation. 29. The use of an anti-AIDS amine of formula (X) for the preparation of a medicament according to claim 1. For the treatment of 26 patients infected with immunodeficiency virus (HIV), the anti-AIDS amine (X) is 1- [indolyl-2-carbonyl] -4- [2-ethoxyphenyl] piperazine. 43