NZ500252A

NZ500252A - 6-(4-Methyl-piperazin-1-yl)-1H-indole derivatives useful as 5HT1A, 5HT1B and 5HT1D receptor antagonists

Info

Publication number: NZ500252A
Application number: NZ500252A
Authority: NZ
Inventors: Paul Adrian Wyman; Laramie Mary Gaster; Harshad Kantilal Rami
Original assignee: Smithkline Beecham P
Priority date: 1997-04-18
Filing date: 1998-04-14
Publication date: 2001-07-27
Also published as: TW509687B; PL336317A1; NO995065D0; JP2001524116A; CN1260781A; IL132409A0; CO4950608A1; NO995065L; AU732863B2; AR013076A1; HUP0001123A2; HUP0001123A3; TR199902590T2; AU7431098A; BR9809092A; CA2288662A1; EP0975593A1; KR20010006487A; WO1998050358A1

Abstract

An indole derivative of formula (I) or a salt thereof is disclosed wherein: Ra is a group of formula (i) or (ii) P1 is phenyl, bicyclic aryl, a 5 to 7 membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur, or a bicyclic heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur; R1 is hydrogen, halogen, alkyl, cycloalkyl, CO-alkyl, alkoxy, hydroxy, hydroxyalkyl, hydroxyalkoxy, alkoxyalkoxy, acyl, nitro, trifluoromethyl, cyano, SR9, SOR9, SO2R9, SO2NR10R11, CO2R10, CONR10R11, CO2NR10R11, CONR10(CH2)cCO2R11, (CH2)cNR10R11, (CH2)cCONR10R11, (CH2)cNR10COR11, (CH2)cCO2alkyl, CO2(CH2)cOR10, NR10R11, NR10CO2R11, NR10CONR10R11, CR10=NOR11, NR10COOR11 CNR10=NOR11; R10 and R11 are independently hydrogen or alkyl; c is 1 to 4; R2 is hydrogen, halogen, alkyl, cycloalkyl, cycloalkenyl, alkoxy, alkanoyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO2R10, CONR10R11, NR10R11; a is 1, 2 or 3; P2 and P3 are independently phenyl, bicyclic aryl, a 5- to 7- membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur, or a bicyclic heterocyclic group containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur; A is a bond or oxygen, S(O)m, carbonyl, CH2, -CH2CH2- or NR4; R4 is hydrogen or alkyl; m is 0 to 2; for formula (ii) R1 can also be an optionally substituted 5 to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur; R2 and R3 are independently hydrogen, halogen, alkyl, cycloalkyl, cycloalkenyl, alkoxy, alkanoyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO2R10, CONR10R11, NR10R11; b is 1, 2 or 3; Y is -NH-, -NR5-, -CH2- or -O-; R5 is alkyl; V is oxygen or sulphur; D is nitrogen, carbon or a CH group; W is (CR16R17)t or (CR16R17)u-J t is 2, 3 or 4; R16 and R17 are independently hydrogen or alkyl; u is 0, 1, 2 or 3; J is oxygen, sulphur, CR16=CR17, CR16=N, =CR16O, =CR16S or =CR16-NR17; X is nitrogen or carbon; Rb is hydrogen, halogen, hydroxy, alkyl, trifluoromethyl, alkoxy, alkenyl, cycloalkyl optionally substituted by alkyl, or aryl; Re is hydrogen or alkyl; the dotted line is a single bond when X is nitrogen or a single or double bond when X is carbon. A pharmaceutical composition thereof is useful for treating CNS disorders.

Description

<div class="application article clearfix" id="description"> c 0 IN7^£ DERIVATIVES HAVING COMBINED 5HT1A, 5HT1B AND 5HT1D RECEPTOR ANTAGONIST ACTIVITY The present invention relates to novel piperazine derivatives, processes for their preparation, and pharmaceutical compositions containing them. 5 WO 95/06637, WO 95/06044 and WO 95/04729 disclose a series of piperazine derivatives which are said to possess 5HT]q receptor antagonist activity. These compounds are alleged to be of use m the treatment of various CNS disorders such as depression. EPA 0533266/7/8 disclose a series of benzanilide derivatives which are said to possess 5-HTid receptor antagonist activity. 10 A structurally distinct class of compounds have now been found to exhibit combined 5HT i a, 5HTjg and 5HT jj) receptor antagonist activity. It is expected that such compounds will be useful for the treatment and prophylaxis of various CNS disorders with the advantage of a relatively fast onset of action. In a first aspect, the present invention therefore provides a compound of formula (I) or a salt thereof: 15 in which Ra is a group of formula (i) <*>®- 20 1 (i) in which P1 is phenyl, bicyclic aryl, a 5 to 7 membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur, or a bicyclic heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur; 25 R.1 is hydrogen, halogen, Cj.^alkyl, Cj.gcycloalkyl, COC^galkyl, C^galkoxy, hydroxy, hydroxyC j .^alkyl, hydroxyC \ .galkoxy, C \ .galkoxyC \ .galkoxy, mtro, tnfluoromethyl, cyano, SR^, SOR^, S02R^, S02NR^®R^, C02R^, - 1 - intellectual property office of nz. 2 0 JUN 2001 received 500252 9 CONR^R11 CO2NR10Rl 1, CONR10(CH2)cCO2R1 (CH2)cNR10Rl * (CH2)cCONR10r11, (CH^CNRIOCOR11, (CH2)cC02C1.6alkyl, CO2(CH2)cOR10, NR10R11,NR10CO2R11,NR10CONR10R11, CRi^NOR^.NRlOcOORll, CNR^=NOR^ 1, where R^, R*0 and R^ are independently hydrogen or C^galkyl and c 5 is 1 to 4, R2 is hydrogen, halogen, C^.galkyl, C3_6cycloalkyl, C3.gcycloalkenyl, Cj.galkoxy, C\_ galkanoyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CCbR^, CONR^R^1, NrIOrI 1 where RlO and R* 1 are independently hydrogen or C,_6 alkyl; a is 1, 2 or 3; 10 or Ra is a group of formula (ii) wherein P- and are independently phenyl, bicyclic aryl, a 5- to 7- membered 15 heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur, or a bicyclic heterocyclic group containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur; A is a bond or oxygen, S(0)m where m is 0 to 2, carbonyl, CH2 , -CH9-CH2-, or NR^ where R4 is hydrogen or Cj.galkyl; 20 Rl is as defined above for formula (i) or R* is a 5 to 7-membered heterocyclic ring, containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur, optionally substituted by Cj.g alkyl, halogen or Cj.g alkanoyl; R- and R^ are independently hydrogen, halogen, C \ .galkyl, C3_6cycloalkyl, C3_6cycloalkenyl, Cj.galkoxy, Ci.galkanoyl, aryl, acyloxy, hydroxy, nitro, 25 trifluoromethyl, cyano, C02R^, CONR^R* 1, NR^R^ 1 where R^ and r1 1 are independently hydrogen or alkyl; and a and b are independently 0,1, 2 or 3; Y is -NH-, -MRS. where R^ is C^galkyl, or Y is -CH2- or -0-; 30 V is oxygen or sulphur; Oi) intellectual property office of nz. -2- 2 0 JUN 2001 RECEIVED WO 98/50358 PCT/EP98/02262 D is nitrogen, carbon or a CH group, W is (CR16r17^ where t is 2, 3 or 4 and and are independently hydrogen or Cj.galkyl or W is (CR^R^)U-J where u is 0, 1, 2 or 3 and J is oxygen, sulphur, CR16=cr17; CR^=N, =CR^O, =CR^S or =CR1^-NR1^, X is nitrogen or carbon; 5 Rb is hydrogen, halogen, hydroxy, Cj.^alkyl, trifluoromethyl, Ci.galkoxy, C2-6alkenyl, C3-7cycloalkyl optionally substituted by C^alkyl, or aryl; Rc is hydrogen or Cj.galkyl, and — is a single bond when X is nitrogen or a single or double bond when X is carbon 10 Ci_6alkyl groups whether alone or as part of another group may be straight chain or branched. The term 'acyloxy' is used herein to descnbe a group -0C(0)Cj_galkyl The term 'aryl' is used herein to descnbe, unless otherwise stated, a group such as phenyl The term 'aralkyl' is used herein to descnbe, unless otherwise stated, a group such as benzyl. The bicyclic aryl group represented by P*, and/or p3, which may be partially 15 saturated, is preferably naphthyl. Examples of bicyclic heterocyclic nngs containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur include isoqumoline, indole, benzofiiran, benzothiophene and preferably quinoline. Examples of 5 to 7 membered heterocyclic nngs contaimng 1 to 3 heteroatoms 20 selected from oxygen, nitrogen and sulphur represented by P 1, P^ and/or P^, include thienyl, furyl, pyrrolyl, tnazolyl, lmidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl, thiadiazolyl, pynmidyl, pyndazinyl and pyrazinyl, and preferably pyridyl The heterocyclic nngs as described above can be linked to the remainder of the 25 molecule via a carbon atom or, when present, a suitable nitrogen atom. Such nngs can also be saturated or partially saturated. Examples of saturated or partially saturated 5 to 7 membered heterocyclic nngs include piperidine, pyrrolidine and morphohne Examples of partially saturated bicyclic heterocyclic rings include dihydrobenzofuran, dihydrobenzothiophene, tetrahydroquinioline and tetrahydroisoquinoline 30 Rl is preferably a halogen atom for example, fluonne, chlonne or bromine, and R^ and/or R^ are each preferably hydrogen, halogen for example a chloro group, or a Cj_ galkyl group for example a methyl group When R* is 5 to 7-membered heterocyclic rings suitable optional substituents include alkyl, alkanoyl and halogen -3 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 a and b are each preferably 1 or 2 A is preferably a bond or oxygen, most preferably a bond. Y is preferably -NH- V is preferably oxygen 5 D is preferably nitrogen and the group W is preferably a (CRJ 6r17){ group where R'6 and Rl? are each advantageously hydrogen and t is suitably 2. Rb is preferably hydrogen or a halogen atom for example chlonne, a Ci.galkoxy group for example methoxy or a Cj.galkyl group such as methyl or ethyl. X is preferably nitrogen 10 Rc is preferably a C j .galkyl group for example methyl Particularly preferred compounds according to the invention include -l-[(4-bromo-3-methylphenyl)aminocarbonyl]-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole, 15 1 -[(4-bromo-3-methylphenyl)aminocarbonyl]-2,3-dihydro-5-methoxy-6-(4-methylpiperazm-1 -yl)-1 H-indole, l-[(2,3-dichlorophenyl)aminocarbonyl]-2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-mdole, 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)naphth-l-20 ylammocarbonyl]-lH-mdole, 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-1 -yl)-1 -[5-(pyridin-4-yl)naphth-1 -ylaminocarbonyl]-lH-mdole, l-[2,3-Dichloro-4-(pyndin-4-yl)phenylaminocarbonyl]-2,3-dihydro-5-methoxy-6-(4-methylpiperazm-1 -y 1)-1 H-indole, 25 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l-(qumolin-5-ylaminocarbonyl)-lH-indole, 2,3-Dihydro-6-(4-methylpiperazm-1 -yl)-l -[4-(pyridin-4-yl)naphth-1 -ylaminocarbonyl]-lH-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(pyridin-4-yl)naphth-1 -30 ylammocarbonyl]-1 H-indole, 5 -Bromo-2,3 -dihydro-6-(4-methylpiperazm-1 -yl)-1 -[4-(pyndin-4-yl)naphth-1 -ylammocarbonyl]-1 H-indole Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)phenylammocarbonyl]-lH-mdole, 5-Bromo-1 -[3 -chloro-4-(pyridin-4-yl)phenylammocarbonyl] -2,3 -dihydro-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5 2,3-Dihydro-5-methyl-6-(4-methylpiperazin-1 -yl)-1 -[4-(pyridin-4-yl)naphth-1 -ylammocarbonyl]-1 H-indole, l-[3-Chloro-4-(pyridin-4-yl)phenylaminocarbonyl]-2,3-dihydro-5-methyl-6-(4-methylpiperazin-1 -yl)-1 H-indole, 2,3-Dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)naphth-l-ylaminocarbonyl]-5-10 vinyl-lH-mdole, 2,3-Dihydro-5-ethyl-6-(4-methylpiperazm-l-yl)-l-[4-(pyridm-4-yl)naphth-l-ylammocarbonyl] -1 H-mdole, l-[3-Chloro-4-(pyridin-4-yl)phenylaminocarbonyl]-2,3-dihydro-5-ethyl-6-(4-methylpiperazin-1 -yl)-1 H-mdole, 15 2,3-Dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(pyridin-4-yl)naphth-1 -ylaminocarbonyl]-5-trifluoromethyl-1 H-indole, l-[3-Chloro-4-(pyridin-4-yl)phenylaminocarbonyl]-2,3-dihydro-6-(4-methylpiperazin-l-yl)-5-trifluoromethyl-1 H-indole, 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-1 -yl)-1 -[4-(pyndin-4-yl)naphth-1 -20 ylacetyl]-IH-indole, 2,3-Dihydro-5-methoxy-6-(4-methylpiperazm-l-yl)-l-[5-(pyridm-4-yl)-naphth-l-ylacetyl]-1 H-indole, 2,3-Dihydro-6-(4-methylpiperazm-1 -yl)-1 -[4-(pyridin-4-yl)naphth-1 -ylacetyl]- IH-indole 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(pyridin-4-yl)naphth-1 -ylacetyl]-25 IH-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazm-1 -yl)-1 -[4-(pyridin-4-yl)naphth-1 -ylacetyl] -IH-indole, 2,3-Dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(pyridin-4-yl)naphth-1 -ylacetyl]-5-vinyl-1 H-mdole, 30 5-Bromo-2,3-dihydro-6-(l -methylpiperidin-4-yl)-1 -[4-(pyndin-4-yl)naphth-1 -ylammocarbonyl] -1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[5-(pyndin-4-yl)naphth-1 -ylammocarbonyl]-1 H-indole, Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Bromo-2,3-dihydro-6-(4-methylpiperazm-1 -yl)-1 -[5-(pyridm-4-yl)naphth-1 -ylammocarbonyl]-1 H-mdole, 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l-(qumohn-6-ylaminocarbonyl)-lH-mdole, 5 2,3-Dihydro-l-[4-(r-butoxycarbonylammo)phenylaminocarbonyl]-5-chloro-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazm-1 -yl)-1 -(quinolin-6-ylammocarbonyl)-1H-mdole, 6-Bromo-7-(4-methylpiperazin-1 -yl)-l -[4-(pyridin-4-yl)naphth-1 -ylammocarbonyl]-10 1,2,3,4-tetrahydroquinoline, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-(4-phenoxyphenylaminocarbonyl)-lH-indole 5-Chloro-2,3-dihydro-l-[4-(4-chlorophenoxy)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 15 5 -Chloro-2,3 -dihydro-6-(4-methylpiperazin-1 -yl)-1 -(qumohn-6-ylammocarbonyl)-1H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazm-l-yl)-l-(3-phenoxyphenylammocarbonyl)-1 H-mdole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pynmidin-2-yl)phenylamino-20 carbonyl]-l H-indole, l-(3-Benzoylphenylammocarbonyl)-5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole, 1 -(4-Benzoylphenylammocarbonyl)-5-chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)- 1H-indole, 25 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-(2-methylquinolin-6-ylaminocarbonyl)-lH-indole, 5-Chloro-2,3-dihydro-l -[4-(fur-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-mdole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(thien-2-yl)phenylammocarbonyl]-30 1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[5-(pyridin-2-yl)naphth-l-ylacetyl]-1 H-indole, Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Bromo-2,3-dihydro-6-(4-methylpiperazm-1 -yl)-1 -[5-(pyndm-4-yl)naphth-1 -ylacetyl]-1 H-mdole, 5-Chloro-2,3-dihydro-l -[4-(l -methylpipendm-4-yl)naphth-1 -ylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5 5-Chloro-2,3-dihydro-l-[4-(2-methyloxazol-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)- IH-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(2-methylpyndin-4-yl)phenylammo-carbonyl]-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(2-methylpyndm-4-10 yl)phenylaminocarbonyl]-1 H-mdole, 5-Chloro-2,3-dihydro-l-[4-(2,6-dimethylpyndin-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Bromo-2,3-dihydro-l-[4-(2,6-dimethylpyndin-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 15 2,3-Dihydro-l-[4-(2,6-dimethylpyndin-4-yl)phenylammocarbonyl]-5-methoxy-6-(4-methylpiperazm-1 -yl)-1 H-mdole, 5-Chloro-2,3-dihydro-l-[4-(2,6-dimethylpyridin-3-yl)phenylammocarbonyl]-6-(4-methylpiperazm-1 -yl)-1 H-indole, 5-Bromo-2,3-dihydro-l-[4-(2,6-dimethylpyndin-3-yl)phenylammocarbonyl]-6-(4-20 methylpiperazin-1 -yl)-1 H-mdole, 2,3-Dihydro-l-[4-(2,6-Dimethylpyndin-3-yl)phenylaminocarbonyl]-5-methoxy-6-(4-methylpiperazin-1 -yl)-1 H-mdole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(5-methyl-l,2,4-oxadiazol-3 -yl)phenylammocarbonyl]-1 H-indole, 25 5-Chloro-2,3-dihydro-l-[4-(3-methyl-l,2,4-oxadiazol-5- yl)phenylaminocarbonyl]-6-(4-methylpiperazm-l-yl)-lH-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[3-(pynmidin-2-yloxy)phenylaminocarbonyl]-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-{4-[N-methyl-N-(pyrimidm-30 2-yl)amino]phenylaminocarbony 1} -1 H-indole, 5-Bromo-2,3-dihydro-l-[4-(fur-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)~ 1 H-indole, -7- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Chloro-2,3-dihydro-6-(4-methylpiperazm-l-yl)-l-[4-(thien-3-yl)phenylaminocarbonyl]-1 H-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(thiazol-2-yl)phenylamino-carbonyl]-1 H-indole, 5 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(thiazol-2-yl)phenylammo-carbonyl]-1 H-mdole, l-[4-(5-Acetylthien-2-yl)phenylaminocarbonyl]-5-chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 H-indole, l-(5-Bromonaphth-l-ylacetyl)-5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-10 1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-(8-phenylqumolin-5-ylaminocarbonyl)-1 H-mdole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -(8-phenylquinolin-5 -ylammocarbonyl)-1 H-indole, 15 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[2-(2-phenylethyl)quinolin-6-ylaminocarbonyl]-1 H-mdole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazm-1 -yl)-1 -[5-(l -methylpiperidin-4-yl)naphth-1 -ylammocarbonyl]- lH-mdole, 5-Bromo-2,3-dihydro-l-[4-(isoqumolm-4-yl)phenylammocarbonyl]-6-(4-20 methylpiperazin-1 -yl)-1 H-indole, 5-Chloro-2,3-dihydro-l-[4-(isoquinolm-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazm-1 -yl)-1 H-mdole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazm-1 -yl)-1 -[4-(qumolin-3-yl)phenylammocarbonyl]-1 H-indole, 25 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(qumohn-3-yl)phenylaminocarbonyl)]-1 H-indole, 5 -Chloro-2,3 -dihydro-6-(4-methylpiperazm-1 -yl)-1 - [(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)aminocarbonyl]-lH-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[(2-methyl-l,2,3,4-30 tetrahydroisoquinolin-7-yl)aminocarbonyl]-lH-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazm-l-yl)-l-[4-(quinolin-8-yl)phenylaminocarbonyl]-1 H-indole, -8- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(qumohn-8-yl)phenylammocarbonyl]-1 H-mdole, 5-Chloro-2,3-Dihydro-l-[4-(imidazol-l-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -y 1)-1 H-indole, 5 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(pyndin-4-yl)phenylaminocarbonyl]-lH-mdole, 2,3-Dihydro-5-methoxy-6-(4-methylpiperazm-l-yl)-l-[(8-phenylquinolin-5-yl)ammocarbonyl]-1 H-indole 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[(8-phenylquinolin-4-10 yl)aminocarbonyl]-l H-mdole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[(8-phenylquinolm-4-yl)aminocarbonyl]-1 H-indole, 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l-[(8-phenylqumolin-4-yl)ammocarbonyl]-1 H-indole, 15 5-Chloro-2,3-dihydro-l-[4-(2,6-dimethyl-pyridin-4-yl)-3-methylphenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-mdole, 5-Chloro-2,3-dihydro-l-[3-methyl-4-(6-methylpyridin-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazm-1 -yl)- IH-indole, 5-Bromo-2,3-dihydro-l-[3-methyl-4-(6-methylpyndm-2-yl)phenylaminocarbonyl]-6-(4-20 methylpiperazm-1 -y 1)-1 H-indole, 2,3-Dihydro-5-methoxy-l-[3-methyl-4-(6-methylpyridin-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazm-1 -yl)-1 H-indole, 5-Chloro-2,3-dihydro-l-[5-(6-methylpyndin-2-yl)naphth-l-ylammocarbonyl]-6-(4-methylpiperazm-1 -y 1)-1 H-mdole, 25 2,3-Dihydro-5-methoxy-l-[5-(6-methylpyridxn-2-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-ethylpiperazm-1 -yl)-1 -[4-(pyridin-4-yl)naphth-1 -ylammocarbonyl]-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-ethylpiperazin-1 -yl)-1 -[5-(pyridin-4-yl)naphth-1 -30 ylaminocarbonyl]-lH-indole, 5-Chloro-2,3-dihydro-6-(piperazin-1 -yl)-l -[4-(pyridin-4-yl)naphth-1 -ylammocarbonyl]-1 H-indole hydrochloride, -9- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Chloro-2,3-dihydro-6-(piperazin-1 -yl)-1 -[5-(pyridin-4-yl)naphth-1 -ylammocarbonyl] -1 H-mdole hydrochloride, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-yl)phenylaminocarbonyl]-1 H-mdole, 5 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-yl)phenylaminocarbonyl]-1 H-mdole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazm-1 -yl)-yl)phenylammocarbonyl] -1 H-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazm-1 -yl)-10 yl)phenylammocarbonyl]-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-yl)aminocarbonyl] -1 H-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-yl)aminocarbonyl]-1 H-mdole, 15 5-Chloro-2,3-dihydro-l-[4-(6-methylpyndazin-3-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Bromo-2,3-dihydro-l-[4-(6-methylpyridazin-3-yl)phenylaminocarbonyl]-6-(4-methylpiperazm-1 -yl)-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyndm-3-20 yl)phenylaminocarbonyl]-1 H-mdole, 5-Chloro-2,3-dihydro-l-[4-(5-methyloxazol-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 2,3-Dihydro-5-methoxy-l-[4-(5-methyloxazol-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 25 5-Bromo-2,3-dihydro-1 -[4-(5-methyloxazol-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-mdole, 5-Chloro-2,3-dihydro-l-[4-(l-methylpyrazol-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Bromo-2,3-l-[4-(l-methylpyrazol-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-l-30 yl)-l H-mdole, 5-Chloro-2,3-dihydro-l-[4'-cyano-3'-methylbiphenyl-4-aminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, -10- l-[4-(pyndazm-3-l-[4-(pyndazin-3-l-[4-(pyrazin-2-l-[4-(pyrazin-2-1 -[(2-phenylpyndin-5-1 -[(2-phenylpyndm-5- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Brorno-2,3-dihydro-l-[4'-cyano-3'-methylbiphenyl-4-armnocarbonyl]-6-(4-methylpiperazm-1 -yl)-1 H-indole, 5-Chloro-2,3-dihydro-l-[4-(2-methylpyndin-5-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-lH-mdole, 5 5-Bromo-2,3-dihydro-1 -[4-(2-methylpyridin-5-yl)phenylammocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Chloro-2,3-dihydro-l-[5-(3-methyl-l,2,4-oxadiazol-5-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazm-1 -yl)-1 H-indole, 2,3-Dihydro-5-methoxy-1 -[5-(3-methyl-1,2,4-oxadiazol-5-yl)naphth-1 -ylammocarbonyl]-10 6-(4-methylpiperazin-1 -yl)-1 H-indole. 5-Bromo-2,3-dihdyro-l-[5-(3-methyl-l,2,4-oxadiazol-5-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazm-1 -yl)-1 H-mdole, 5-Chloro-2,3-dihydro-l-[5-(5-methyloxazol-2-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazm-1 -yl)-1 H-indole, 15 2,3-Dihydro-5-methoxy-l-[5-(5-methyloxazol-2-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazm-1 -y 1)-1 H-mdole, 5-Bromo-2,3-dihydro-l-[3-methyl-4-(pyrimidin-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazm-1 -yl)-1 H-mdole, 2,3-Dihydro-5-methoxy-l-[3-methyl-4-(pynmidm-2-yl)phenylammocarbonyl]-6-(4-20 methylpiperazm-1 -yl)-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[3-methyl-4-(pynmidin-2-yl)phenylammocarbonyl]-1 H-indole, 5-Bromo-2,3-dihydro-l-[3-methyl-4-(pyrimidin-5-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 25 5-Chloro-2,3-dihydro-l-[3-methyl-4-(pyrimidin-5-yl)phenylaminocarbonyl]-6-(4-methylpiperazm-1 -yl)-1 H-mdole, 2,3-Dihydro-5-methoxy-l-[3-methyl-4-(pynmidin-5-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Bromo-2,3-dihydro-l-[4-(2,6-dimethylpyndm-4-yl)-3-methylphenylaminocarbonyl]-6-3 0 (4-methylpiperazin-1 -yl)-1 H-mdole, 2,3-Dihydro-5-methoxy-l-[4-(2,6-dimethylpyridin-4-yl)-3-methylphenylaminocarbonyl]- 6-(4-methylpiperazin-1 -yl)-1 H-indole, -11 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Chloro-2,3-dihydro-l-[5-(2,6-dimethylpyridm-4-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Bromo-2,3-dihydro-l-[5-(2,6-dimethylpyridin-4-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-mdole, 5 2,3-Dihydro-l-[5-(2,6-dimethylpyridin-4-yl)naphth-l-ylammocarbonyl]-5-methoxy-6-(4-methylpiperazin-1 -y 1)-1 H-indole or pharmaceutical ly acceptable salts thereof. Preferred salts of the compounds of formula (I) are pharmaceutical^ acceptable salts. These include acid addition salts such as hydrochlorides, hydrobromides, 10 phosphates, acetates, fumarates, maleates, tartrates, citrates, oxalates, methanesulphonates and p-toluenesulphonates Certain compounds of formula (I) are capable of existing in stereoisomenc forms It will be understood that the invention encompasses all geometric and optical isomers of the compounds of formula (I) and the mixtures thereof including racemates. 15 Compounds of the invention can be prepared using procedures known in the art In a further aspect the present invention provides a process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof which comprises-(a) where D is nitrogen and Y is NH , coupling a compound of formula (II): in which Ra and V are as defined in formula (I) or a protected derivative thereof with a compound of formula (III): 25 in which W, X, and Rc are as defined in formula (I), or a protected derivative thereof, 20 Ra _NC(=V) (II) or (b) where D is nitrogen and Y is NH or NR^, reacting a compound of formula (IV) Ra -NH2 or Ra -NR5H (IV) -12- Pnnted from Mimosa WO 98/50358 PCT/EP98/02262 in which Ra and are as defined m formula (I) with a compound of formula (III) together with an appropriate urea forming agent; (c) where D is nitrogen, reacting a compound of formula (V) Ra -Y- (C=0) - L2 (V) 5 in which Ra is as defined in formula (I), Y is -CH2- or -O- and L2 is an appropnate leaving group, with a compound of formula (in); d) where D is carbon or CH, reacting a compoimd of formula (VI) Ra -NH2 (VI) 10 in which Ra is as defined m formula (I) with a compound of formula (VII) ;'R° o (VII) m which D is carbon or CH, W, X, R^ and Rc are as defined m formula (I) and L2 is an appropnate leaving group and optionally thereafter. 15 • removing any protecting groups, • converting a compound of formula (I) into another compound of formula (I), • forming a pharmaceutical^ acceptable salt. The reaction in process (a) is conveniently effected in an organic solvent such as 20 dichloromethane. In process (b) the urea forming agent can be carbonyl dumidazole, tnphosgene or phosgene, and earned out in an inert organic solvent such as dimethylformamide, tetrahydrofuran or dichloromethane at ambient or elevated temperature in the presence of a base such as tnethylamme or pyridine 25 In process (c) the leaving group L2 may be a halogen e.g. chloro group and the reaction may be earned out in an inert organic solvent such as tetrahydrofuran or dichloromethane at ambient or elevated temperature in the presence of a base such as tnethylamme or pyndine. - 13- Printed from Mimosa WO 98/50358 PCT/EP98/02262 In process (d) the leaving group L2 may be a halogen e g. chloro group and the reaction may be earned out in an inert organic solvent such as tetrahydrofuran or dichloromethane at ambient or elevated temperature in the presence of a base such as tnethylamme or pyndine 5 Compounds of formula (I) can be converted into further compounds of formula (I) using standard techniques. For example, m the case wherein Rc is hydrogen, it is possible to introduce a C^.galkyl group by conventional alkylation using 1 molar equivalent of a Cj.galkyl halide and 1 molar equivalent of a suitable base in an inert solvent. 10 Intermediate compounds of formula (II), (III), (IV), (V) ,(VI) and (VII) can be prepared using standard procedures known in the art. It will be appreciated to those skilled in the art that it may be necessary to protect certain reactive substituents dunng some of the above procedures Standard protection and deprotection techniques can be used. For example, pnmary amines can be 15 protected as phthahmide, benzyl, benzyloxycarbonyl or tntyl denvatives. These groups can be removed by conventional procedures well known m the art. Carboxylic acid groups can be protected as esters. Aldehyde or ketone groups can be protected as acetals, ketals, thioacetals or thioketals Deprotection is achieved using standard conditions. 20 5ht l A/IB/ID receptor antagonists, and in particular the compounds of the present invention, are expected to be of use in the treatment of CNS disorders such as mood disorders, including depression, seasonal affective disorder and dysthymia; anxiety disorders, including generalised anxiety, panic disorder, agoraphobia, social phobia, obsessive compulsive disorder and post-traumatic stress disorder, memory disorders, 25 includmg dementia, amnestic disorders and age-associated memory impairment, disorders of eating behaviours, including anorexia nervosa and bulimia nervosa and sleep disorders (including disturbances of Circadian rhythm). Other CNS disorders include motor disorders such as Parkinson's disease, dementia m Parkinson's disease, neuroleptic-induced Parkinsonism and tardive dyskinesias, as well as other psychiatric disorders 30 5htj a/IB/ID receptor antagonists, and in particular compounds of the present invention, may also be of use in the treatment of endocrine disorders such as hyperprolactinaemia, in the treatment of vasospasm (particularly in the cerebral vasculature) and hypertension, as well as disorders in the gastrointestinal tract where - 14- Printed from Mimosa WO 98/50358 PCT/EP98/02262 changes in motility and secretion are involved They may also be of use in the treatment of sexual dysfunction and hypothermia. The present invention also provides a compound of general formula (I) or a physiologically acceptable salt or solvate thereof for use in the treatment of the 5 aforementioned disorders. In a further aspect the invention provides a method of treating the aforementioned disorders which comprises administering an effective amount to a patient in need of such treatment of a compound of general formula (I) or a pharmaceutically acceptable salt or solvate thereof 10 In particular the invention provides a compound of general formula (I) or a physiologically acceptable salt or solvate thereof for use in the treatment or prophylaxis of depression. It will be appreciated by those skilled in the art that the compounds according to the invention may advantageously be used m conjunction with one or more other 15 therapeutic agents, for instance, different antidepressant agents. The present invention also provides a pharmaceutical composition, which compnses a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. A pharmaceutical composition of the invention, which may be prepared by 20 admixture, suitably at ambient temperature and atmospheric pressure, is usually adapted for oral, parenteral or rectal administration and, as such, may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable or infusible solutions or suspensions or suppositories Orally administrable compositions are generally preferred. 25 Tablets and capsules for oral administration may be in unit dose form, and may contain conventional excipients, such as binding agents, fillers, tablettmg lubricants, disintegrants and acceptable wetting agents. The tablets may be coated according to methods well known in normal pharmaceutical practice Oral liquid preparations may be m the form of, for example, aqueous or oily 30 suspension, solutions, emulsions, syrups or elixirs, or may be in the form of a dry product for reconstitution with water or other suitable vehicle before use Such liquid preparations may contain conventional additives such as suspending agents, emulsifying - 15- Printed from Mimosa WO 98/50358 PCT/EP98/02262 agents, non-aqueous vehicles (which may include edible oils), preservatives, and, if desired, conventional flavourings or colorants. For parenteral administration, fluid unit dosage forms are prepared utilising a • compound of the invention or pharmaceutically acceptable salt thereof and a sterile 5 vehicle. The compound, depending on the vehicle and concentration used, can be either suspended or dissolved in the vehicle. In preparing solutions, the compound can be dissolved for injection and filter sterilised before filling into a suitable vial or ampoule and sealing. Advantageously, adjuvants such as a local anaesthetic, preservatives and buffenng agents are dissolved in the vehicle. To enhance the stability, the composition 10 can be frozen after filling into the vial and the water removed under vacuum Parenteral suspensions are prepared in substantially the same manner, except that the compound is suspended in the vehicle instead of being dissolved, and sterilisation cannot be accomplished by filtration. The compound can be sterilised by exposure to ethylene oxide before suspension in a sterile vehicle. Advantageously, a surfactant or wetting 15 agent is included in the composition to facilitate uniform distribution of the compound The composition may contain from 0.1% to 99% by weight, preferably from 10 to 60% by weight, of the active material, depending on the method of administration The dose of the compoimd used in the treatment of the aforementioned disorders will vary m the usual way with the seriousness of the disorders, the weight of the sufferer, 20 and other similar factors. However, as a general guide suitable unit doses may be 0 05 to 1000 mg, more suitably 1 0 to 200 mg, and such unit doses may be administered more than once a day, for example two or three a day Such therapy may extend for a number of weeks or months. The following Examples illustrate the preparation of compounds of the invention 25 Description 1 4-Bromo-3-methylphenyl isocyanate To a stirred suspension of 4-bromo-3-methylbenzoic acid (lO.Og, 0.047 mole) m dichloromethane (300ml) was added oxalyl chloride (11.94g, 0.094 mole) followed by 3 30 drops of DMF. The mixture was stirred at room temperature for 60h, then the solution was concentrated in vacuo to afford the acid chloride as a red oil This material was redissolved in dichloromethane (300ml) and cooled to 0°C. Tetrabutylammomum iodide (0.150g) was added, followed by a solution of sodium azide (4.36g, 0.066 mole) in water -16- Pnnted from Mimosa WO 98/50358 PCT/EP98/02262 (75ml) and the mixture was stirred vigorously at 0°C for 3h, then diluted with water (200ml) and the dichloromethane layer separated, dried (Na2S04) and concentrated in vacuo (but not to complete dryness) to afford the acyl azide as a pale orange solid. This matenal was dissolved in toluene (300ml) and heated under reflux for lh with stirring, 5 then cooled and concentrated in vacuo to afford the title compound as a red brown oil (9 42g, 95%) 'H NMR (250MHz, CDC13) 5 (ppm): 7.54 (d, 1H), 7.06 (d, 1H), 6.88 (dd, 1H), 2.46 (s, 3H) 10 Description 2 4-(Pyridin-4-yl)naphth-l-ylamine A stirred suspension of 4-bromonaphth-l-ylamine (lOg, 45 mmole) in 1,2-dimethoxyethane (400 ml) and water (100 ml) containing sodium carbonate (14g) was flushed with argon for 0.3h. Tetrakis(tnphenylphosphine)palladium (0) (2 75g, 2 4 15 mmole) was added followed by 4-pyridylboronic acid (5 7g, 46 mmole) and the mixture heated at reflux for 5h The mixture was concentrated in vacuo to a brown slurry and partitioned between dichloromethane and water The aqueous was further extracted with dichloromethane and the combined organics dned (Na2S04) and concentrated in vacuo to a brown solid (13 2g) Purification of the solid by flash chromatography eluting with 20 ethyl acetate afforded the title compound as a yellow crystalline solid (7.8g, 78%) *H NMR (250 MHz, CDC13) 5 (ppm). 8.68 (d, 2H), 7.90 (d, 2H), 7.30 (m, 5H), 6.84 (d, 1H), 4.32 (s, 2H) Description 3 25 5-(Pyridin-4-yl)-l-naphthoic acid The title compoimd was prepared from 5-bromo-l-naphthoic acid (EP 547442 Al) and 4-pyridylboronic acid using a similar procedure to Description 2. !h NMR (250 MHz, d6DMSO) 5 (ppm): 8.75 (d, 1H), 8.56 (dd, 2H), 7.98 (d, 1H), 7.78 (d, 1H), 7 56 (t, 1H), 7 45-7.34 (m, 4H) 30 Description 4 5-(Pyridin-4-yI)naphth-l-yl isocyanate -17- Printed from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 5-(pyridin-4-yl)-l-napthoic acid (D3) using a similar procedure to Description 1. . lH NMR (250 MHz, CDCI3) 8 (ppm): 8.74 (d, 2H), 8.21 (d, 1H), 7.61-7.69 (m, 2H), 7.49-7.33 (m, 5H) 5 Description 5 4-(Pyridin-4-yl)aniline The title compound was prepared from 4-bromoanilme and 4-pyndinylboromc acid using a similar procedure to Descnption 2 as a white solid (17%) 10 *H NMR (250 MHz, d6DMSO) 5 (ppm). 8.68-8.63 (m, 2H), 7.78-7 68 (m, 4H), 6 84 (d, 2H), 5.94 (br s, 2H). Description 6 3-Chloro-4-(pyridin-4-yl)aniIine 15 3-Chloro-4-bromoacetamlide was reacted with 4-pyndmylboronic acid using a similar procedure to Descnption 2 to afford 3-chloro-4-(pyndm-4-yl)acetanilide. This matenal was hydrolysed by heating under reflux in a mixture of 2M NaOH solution and ethanol for 6h to afford the title compound as a pale yellow solid (5.5g, 73%). !h NMR (250 MHz, CDCI3) 5 (ppm) 8 65-8 58 (m, 2H), 7.38-7 33 (m, 2H), 7 13 (d, 20 1H), 6.80 (d, 1H), 6.64 (dd, 1H), 3.90 (br s, 2H) Description 7 2,3-Dichloro-4-(pyridin-4-yl)aniline The title compound was prepared from 4-bromo-2,3-dichloroacetanilide and 4-25 pyridinylboromc acid, followed by basic hydrolysis, using a similar procedure to the preparation of Description 6. lU NMR (250 MHz, CDCI3) 5 (ppm): 8.64 (d, 2H), 7 32 (d, 2H), 7 05 (d, 1H), 6.85 (d, 1H), 4 40 (br s, 2H). 30 Description 8 1 -Acetyl-2,3-dihydro-6-nitro-l H-indole A stirred solution of 2,3-dihydro-6-nitro-lH-mdole (lOOg, 0.61 mole) in dichloromethane (1000 ml) at room temperature was treated dropwise over 20 mm with acetic anhydnde -18- Printed from Mimosa WO 98/50358 PCT/EP98/02262 (62 ml, 0 66 mole) The reaction mixture was stirred for a further 2h, then washed with 10% Na2CC>3 solution (300 ml) dried (Na2SC>4) and concentrated in vacuo to afford the title compound as a yellow solid (125g, 100%). 5 Description 9 l-Acetyl-6-amino-2,3-dihydro-lH-indole A stirred suspension of l-acetyl-2,3-dihydro-6-nitro-lH-mdole (D8, 125g, 0 61 mole) in THF (5500 ml) was hydrogenated over 10% Pd-C (20g) at 50 psi for 20h The catalyst was removed by filtration through a plug of kieselguhr and the filtrate concentrated in 10 vacuo to afford the title compound as a beige solid (102g, 95%). !h NMR (250 MHz, CDC13) 5 (ppm): 7.64 (d, 1H), 6 92 (d, 1H), 6 34 (dd, 1H), 4 01 (t, 2H), 3 82 (br s, 2H), 3.06 (t, 2H), 2.19 (s, 3H). Description 10 15 l-Acetyl-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indoIe A stirred mixture of l-acetyl-6-amino-2,3-dihydro-lH-indole (D9, 37.8g, 0.22 mole), mechlorethamine hydrochloride (46g, 0 24 mole) and anhydrous potassium carbonate (80g, 0.58 mole) in 1-butanol (1800 ml) was heated at reflux for 8h, then additional mechlorethamine hydrochloride (25g, 0.13 mole) and potassium carbonate (41g, 0.30 20 mole) were added and reflux continued for 3h. The reaction mixture was allowed to cool and then washed with water (1000 ml). The aqueous wash was extracted with ethyl acetate, and the extract combined with the 1-butanol solution and concentrated in vacuo The brown oily residue (60g) was chromatographed on silica gel elutmg with 0-8% MeOH/DCM to give an orange oil, which was tntuated with ether to afford the title 25 compound as a beige solid (12 2g, 22%) !h NMR (250 MHz, CDCI3) 5 (ppm). 7.98 (d, 1H), 7 04 (d, 1H), 6 59 (dd, 1H), 4 04 (t, 2H), 3.23-3.18 (m, 4H), 3.10 (t, 2H), 2.60-2.53 (m, 4H), 2.34 (s, 3H), 2.21 (s, 3H) Description 11 30 2,3-Dihydro-6-(4-methyIpiperazin-l-yl)-lH-indole The title compound was prepared from l-acetyl-2,3-dihydro-6-(4-methylpiperazin-l-yl)-1 H-indole (D10) using a similar procedure to Description 13 as a beige solid (92%) -19- Pnnted from Mimosa WO 98/50358 PCT/EP98/02262 NMR (250 MHz, CDCI3) 8 (ppm): 6 98 (dd, 1H), 6 34-6.27 (m, 2H), 3 53 (t, 2H), 3 32 (br s, 1H), 3 17-3.11 (m, 4H), 2.94 (t, 2H), 2.61-2 52 (m, 4H), 2.34 (s, 3H) Description 12 5 l-Acetyl-5-chloro-2,3-dihydro-6-(4-methyIpiperazin-l-yl)-lH-indole A stirred solution of l-acetyl-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D10, l.lg, 0.0040 mole) in dichloromethane (100 ml) at -5°C under argon was treated dropwise over 15 mm with a solution of N-chlorosuccimmide (0 73g, 0 0054 mole) in DCM (10 ml), then kept at -5°C for a further 0.5h and allowed to warm to room 10 temperature over lh. The reaction mixture was extracted with 2M HC1 acid (60 ml) and the acid extract basified by addition of solid K2CO3 and extracted with DCM. The organic extract was dried (Na2S04) and concentrated in vacuo to afford the title compound as a beige solid (1.45g, 100%) lH NMR (250 MHz, CDCI3) 8 (ppm). 8.05 (s, 1H), 7.15 (s, 1H), 4.06 (t, 2H), 3 20-3 05 15 (m, 4H), 3 12 (t, 2H), 2 70-2.55 (m, 4H), 2.37 (s, 3H), 2.22 (s, 3H). Description 13 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole A stirred solution of l-acetyl-5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-mdole 20 (D12,1.4g, 0.0048 mole) m 2M HC1 acid (120 ml) was heated at reflux under argon for 5h The reaction mixture was allowed to cool, basified by addition of solid K2C03 and extracted with DCM The extract was dried (Na2SC>4) and concentrated in vacuo to afford the title compound as a beige solid (0 93g, 78%) !h NMR (250 MHz, CDCI3) 8 (ppm): 7.07 (s, 1H), 6 40 (s, 1H), 3 76 (br s, 1H), 3.56 (t, 25 2H), 3.01 (br s, 4H), 2.96 (t, 2H), 2.60 (br s, 4H), 2.35 (s, 3H). Description 14 l-Acetyl-5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole A stirred mixture of l-acetyl-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l H-mdole (D10, 30 2.0g, 0 0077 mole) and anhydrous potassium carbonate (2.12g, 0.015 mole) in a mixture of dichloromethane (100 ml) and methanol (50 ml) at -5°C under argon was treated portionwise over 20 min with benzyltnmethylammonium tnbromide (3 14g, 0 0081 mole). The mixture was allowed to warm to room temperature over lh, then concentrated -20- Printed from Mimosa WO 98/50358 PCT/EP98/02262 in vacuo and the residue dissolved in dichloromethane (150 ml), washed with water (2x100 ml), dried (Na2SC>4) and concentrated in vacuo to afford the title compound as a beige solid (2.52g, 97%). lH NMR (250 MHz, CDCI3) 8 (ppm) 8 06 (s, 1H), 7.34 (s, 1H), 4.06 (t, 2H), 3 13 (t, 5 2H), 3 07 (br s, 4H), 2 06 (br s, 4H), 2 35 (s, 3H), 2 21 (s, 3H) Description 15 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole A solution of l-acetyl-2,3-dihydro-5-bromo-6-(4-methylpiperazin-l-yl)-lH-indole (D14, 10 0 60g, 1 8 mmole) m 2M hydrobromic acid (50 ml) was stirred at room temperature for 5 days, then basified by addition of solid K2CO3 and extracted with DCM The extract was dried (Na2SC>4) and concentrated in vacuo to afford the title compound as a brown solid (0.3 lg, 58%) lH NMR (250 MHz, CDCI3) 8 (ppm). 7.24 (s, 1H), 6.42 (s, 1H), 3.80 (br s, 1H), 3.56 (t, 15 2H), 3 01-2.92 (m, 6H), 2.59 (br s, 4H), 2.35 (s, 3H). Description 16 l-Acetyl-2,3-dihydro-5-methyl-6-(4-methylpiperazin-l-yI)-lH-indole The title compound was prepared from l-acetyl-2,3-dihydro-5-bromo-6-(4-20 methylpiperazin-l-yl)-lH-indole (D14) and tetramethyltin using a similar procedure to Descnption 18 as a beige solid (63%). !h NMR (250 MHz, CDCI3) 8 (ppm). 8 0 (s, 1H), 6 98 (s, 1H), 4 02 (t, 2H), 3.11 (t, 2H), 2.97-2.92 (m, 4H), 2.56 (br s, 4H), 2.35 (s, 3H), 2 25 (s, 3H), 2.20 (s, 3H). 25 Description 17 2,3-Dihydro-5-methyl-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from l-acetyl-2,3-dihydro-5-methyl-6-(4-methylpiperazin-l-yl)-lH-indole (D16) using a similar procedure to Description 13 as a beige solid (89%). 30 ]H NMR (250 MHz, CDCI3) 8 (ppm): 6.94 (s, 1H), 6 44 (s, 1H), 3 52 (t, 2H), 2 95 (t, 2H), 2.92-2.86 (m, 4H), 2.55 (br s, 4H), 2.35 (s, 3H), 2.19 (s, 3H). Description 18 -21 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 l-Acetyl-2,3-dihydro-6-(4-methyIpiperazin-l-yl)-5-vinyl-lH-indoIe A stirred suspension of l-acetyl-2,3-dihydro-5-bromo-6-(4-methylpiperazin-l-yl)-lH-mdole (D14, 600 mg, 1 8 mmole) in dry DMF (15 ml) was treated with vinyltnbutyltm (0.78 ml, 2 7 mmole) and de-gassed by bubbling argon through for 20 mm, then 5 triethylamine (0.50 ml, 3.6 mmole) and tetrakis(tnphenylphosphine)palladium(0) (200 mg) were added and the mixture was heated at 100°C under argon for 7 h The reaction mixture was allowed to cool, diluted with EtOAc (150 ml), then extracted with 0 5M HCl acid (2 x 100 ml) The acid extract was basified by addition of solid K2CO3, then extracted with DCM (2 x 100 ml) and the extract dried (Na2S04) and concentrated in 10 vacuo to afford the title compound as a beige solid (480 mg, 95%) iH NMR (250 MHz, CDCI3) 6 (ppm):7 99 (s, 1H), 7.31 (s, 1H), 7 00 (dd, 1H), 5.58 (dd, 1H), 5.14 (dd, 1H), 4.05 (t, 2H), 3.14 (t, 2H), 3.02-2.94 (m, 4H), 2 57 (br s, 4H), 2 35 (s, 3H), 2 22 (s, 3H) 15 Description 19 2,3-Dihydro-6-(4-methylpiperazin-l-yl)-5-vinyI-lH-indole A stirred solution of l-acetyl-2,3-dihydro-6-(4-methylpiperazin-l-yl)-5-vinyl-l H-mdole (D18, 250 mg, 9.0 mmole) in ethanol (25 ml) was treated with 10% NaOH solution (45 ml), de-gassed by bubbling argon through for 15 mm, then heated under reflux for 7 h 20 The mixture was allowed to cool, concentrated in vacuo to approx 40 ml volume and then extracted with DCM. The extract was dried (Na2SC>4) and concentrated in vacuo to afford the title compound as a brown solid (170 mg, 80%). !h NMR (250 MHz, CDCI3) 5 (ppm). 7.30 (s, 1H), 6 98 (dd, 1H), 6.38 (s, 1H), 5.49 (dd, 1H), 5.01 (dd, 1H), 3.81 (br s, 1H), 3 56 (t, 2H), 2.99 (t, 2H), 2.96-2.90 (m, 4H), 2.56 (br 25 s, 4H), 2.35 (s, 3H). Description 20 l-AcetyI-2,3-dihydro-5-ethyl-6-(4-methyIpiperazin-l-yl)-lH-indole A stirred solution of l-acetyl-2,3-dihydro-6-(4-methylpiperazin-l-yl)-5-vinyl-lH-mdole 30 (D18,400 mg, 1.4 mmole) m ethanol (100 ml) was hydrogenated over 10% Pd-C (100 mg) at atmospheric pressure and temperature for 24 h. The catalyst was removed by filtration through kieselguhr and the filtrate concentrated in vacuo to afford the title compoimd as a beige solid (380 mg, 94%). -22- Printed from Mimosa WO 98/50358 PCT/EP98/02262 JH NMR (250 MHz, CDCI3) 8 (ppm). 8 05 (s, 1H), 7.03 (s, 1H), 4.03 (t, 2H), 3 13 (t, 2H), 2.96-2.90 (m, 4H), 2 65 (q, 2H), 2 57 (br s, 4H), 2 35 (s, 3H), 2.20 (s, 3H), 1.21 (t, 3H). * 5 Description 21 2,3-Dihydro-5-ethyl-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from l-acetyl-2,3-dihydro-5-ethyl-6-(4-methylpiperazm-l-yl)-lH-mdole (D20) using a similar procedure to Description 13 as a beige solid (94%) 10 !h NMR (250 MHz, CDCI3) 8 (ppm)' 6 99 (s, 1H), 6 49 (s, 1H), 3 6 (br s, 1H), 3.53 (t, 2H), 2 97 (t, 2H), 2.90-2.83 (m, 4H), 2 59 (q, 2H), 2.54 (br s, 4H), 2 35 (s, 3H), 1 19 (t, 3H). Description 22 15 l-Acetyl-2,3-dihydro-6-(4-methylpiperazin-l-yI)-5-trifluoromethyl-lH-indole A stirred mixture of l-acetyl-5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-mdole (D14, 500 mg, 1 5 mmole), potassium trifluoroacetate (410 mg, 2.7 mmole) and copper (I) iodide (572 mg, 3.0 mmole) m dry DMF (16 ml) and toluene (10 ml) was heated at 130°C for 0.5 h under argon using a Dean and Stark head to trap toluene/water The 20 Dean and Stark head was replaced with a condenser and the mixture heated at 155°C for 34 h, then further potassium trifluoroacetate (410 mg) and copper (I) iodide (570 mg) were added and heating continued at 155°C for 3h. The reaction mixture was allowed to cool, then treated with dilute ammonia solution (200 ml) and DCM (150 ml), shaken well and then filtered through a plug of kieselguhr The organic layer was separated, dned 25 (Na2SC>4) and concentrated in vacuo. The residue was purified by chromatography on basic alumina elutmg with ethyl acetate to afford the title compound as a beige solid (63%) *H NMR (250 MHz, CDCI3) 8 (ppm): 8.28 (s, 1H), 7.40 (s, 1H), 4 10 (t, 2H), 3 18 (t, 2H), 2 98-2.92 (m, 4H), 2 56 (br s, 4H), 2.35 (s, 3H), 2.24 (s, 3H) 30 Description 23 2,3-Dihydro-6-(4-methyIpiperazin-l-yl)-5-trifluoromethyl-lH-indole -23 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 A solution of l-acetyl-2,3-dihydro-6-(4-methylpiperazm-l-yl)-5-trifluoromethyl-lH-indole (D22, 260 mg, 1.1 mmole) in 2M HCl acid (25 ml) and ethanol (25 ml) was kept at room temperature for 7 days, then concentrated in vacuo to approx. 25 ml volume The aqueous residue was basified with solid K2CO3, then extracted with DCM and the extract 5 dried (Na2SC>4) and concentrated in vacuo to afford the title compound as a beige solid (300 mg, 91%) lH NMR (250 MHz, CDCI3) 8 (ppm)- 7.30 (s, 1H), 6.57 (s, 1H), 4 01 (br s, 1H), 3 63 (t, 2H), 3 01 (t, 2H), 2 92-2.85 (m, 4H), 2 54 (br s, 4H), 2.34 (s, 3H) 10 Description 24 4-(Pyridin-4-yl)n aphth-1 -ylacetic acid 4-Bromonaphth-l-ylacetic acid (lg, 3 78 mmole, J Org. Chem., 1951, 16, 1588) in 1,2-dimethoxyethane (50 ml) was treated with pyndin-4-ylboronic acid (465 mg, 3.78 mmole), sodium hydrogen carbonate (952 mg, 11 3 mmole) and water (10 ml). A stream 15 of argon was bubbled through the mixture for 15 min, then tetrakis (tnphenylphosphine) palladium (0) (200 mg, 0 17 mmole) was added and the mixture heated under reflux for 18h. The mixture was then concentrated in vacuo to a gum, which was partitioned between 2M sodium hydroxide solution and dichloromethane. The aqueous layer was separated, adjusted to pH 7 by addition of aqueous potassium carbonate solution and 20 extracted with dichloromethane. The dichloromethane extract was dried (Na2S04) and concentrated in vacuo to give the title compound, which crystallised from ether as needles mp 210-215°C (465 mg, 46%) *H NMR (250 MHz, CDCI3) 8 (ppm): 8 55 (d, 2H), 8.0 (d, 1H), 7.7 (d, 1H), 7.5-7.3 (m, 5H), 7.2 (d, 1H), 6 1 (br s, 1H), 4.0 (s, 2H) 25 Description 25 5-(Pyridin-4-yl)napth-l -ylacetic acid The title compound was prepared from 5-bromonaphth-l-ylacetic acid (Bull Soc. Chim. Fr., 1968, 7, 2957) and pyridin-4-ylboronic acid using a similar procedure to Description 30 24. ^ NMR (250 MHz, CDCI3) 8 (ppm): 8.72 (d, 2H), 8.13 (d, 1H), 7.76 (d, 1H), 7 60 (t, 1H), 7.40-7.50 (m, 3H), 7.44 (d, 2H), 4.12 (s, 2H). -24- Printed from Mimosa WO 98/50358 PCT/EP98/02262 Description 26 Quinolin-6-yl isocyanate The title compoimd was prepared from 6-quinohnecarboxylic acid using a similar procedure to Descnption 1. 5 'H NMR (250 MHz, CDC13) 8 (ppm): 8 89 (dd, 1H), 8.13 - 8 06 (m, 2H), 7.52 (d, 1H), 7 48 - 7.41 (m, 2H). Description 27 3-(4-Methylpiperazin-l-yl)-l-nitrobenzene 10 To a solution of 3-nitroaniline (15.0g, 0.11 mole) m 2-butanol (500ml) was added K2C03 (52.5g, 0 385 mole) and mechlorethamine hydrochloride (31 4g, 0.16 mole) The mixture was refluxed under argon with stirring for 18h, then more mechlorethamine hydrochlonde (17 5g, 0.09 mole) and K2C03 (25 Og, 0.18 mole) were added and heating under reflux was continued for 24h The 2-butanol was removed in vacuo and the residue partitioned 15 between H20 (300 ml) and CH2C12 (300ml). The CH2C12 was separated and the aqueous re-extracted with CH2C12 (3 x 200ml) The organics were combined, dned (Na2S04) and-concentrated in vacuo to afford an orange oil, which was purified by column chromatography on silica gel eluting with 0-4% MeOH/CH2Cl2. The title compound was an orange oil (16 72g, 70%). 20 ]H NMR (250 MHz, CDC13) 8 (ppm): 7.72 (d, 1H), 7.65 (dd, 1H), 7.37 (t, 1H), 7 19 (dd, 1H), 3.31 (t, 4H), 2 59 (t, 4H), 2 37 (s, 3H). Description 28 3-(4-Methylpiperazin-l-yl)aniline 25 3-(4-Methylpiperazin-l-yl)-l-nitrobenzene (D27, 8 lOg, 0.037 mole) was dissolved in EtOH (250ml) and hydrogenated over 10% Pd/C (2g) at room temperature and pressure for 18h The catalyst was filtered off and the filtrate concentrated in vacuo to afford the title compound as a pale yellow oil (6.64g, 95%). 'H NMR (250 MHz, CDC13) 8 (ppm)- 7 04 (t, 1H), 6.37 (dd, 1H), 6 26 (d, 1H), 6.21 (dd, 30 1H), 3.60 (br s, 2H), 3.18 (t, 4H), 2.56 (t, 4H), 2.34 (s, 3H). Description 29 7-(4-Methylpiperazin-l-yl)quinoline -25- Printed from Mimosa WO 98/50358 PCT/EP98/02262 3-(4-Methylpiperazm-l-yl)anihne (D28, 6.6g, 0.035mole) was covered with glycerol (8ml, 0.1 mole) and conc. H2S04 acid (5.2ml, 0.097 mole) was carefully added dropwise, with stirring, over 10 mm An air condenser was fitted, iodine (lOOmg) added and the reaction heated with stirring at 100°C for 3h, then at 150°C for 4h The reaction was 5 cooled and poured into water (250ml) The aqueous was basified to pHIO with K2C03 and extracted into CH2C12 (3 x 300ml). The orgamcs were combined, dried (Na2S04) and concentrated in vacuo to give a dark brown oil, which was purifed by column chromatography on basic alumina eluting with 2% MeOH/CH2Cl2. The title compound was a yellow solid (4 05g, 52%). 10 'H NMR (250 MHz, CDC13) 8 (ppm): 8.78 (m, 1H), 8 0 (dd, 1H), 7.67 (d, 1H), 7.37 (d, 1H), 7 33 (dd, 1H), 7 19 (dd, 1H), 3 40 (t, 4H), 2.63 (t, 4H), 2.38 (s, 3H). Description 30 7-(4-MethyIpiperazin-l-yl)-l,2,3,4-tetrahydroquinoline 15 7-(4-Methylpiperazm-l-yl)qumoline (D29,371 g, 0016 mole) was dissolved m EtOH (100ml) and AcOH (5ml) and hydrogenated at 50psi and room temperature over 5% Pt/C (1 Og) for 84h. The catalyst was filtered off, the solvents removed in vacuo and the residue partitioned between 10% Na2C03 (aq) and CH2C12. The CH2C12 was separated, dried (Na2S04) and concentrated in vacuo to afford the title compound as a pale 20 orange/brown solid (3.60g, 95%). 'H NMR (250 MHz, CDC13) 8 (ppm): 6.84 (d, 1H), 6.27 (dd, 1H), 6 05 (d, 1H), 3 5 (br s, 1H), 3.27 (t, 2H), 3.12 (t, 4H), 2.68 (t, 2H), 2.55 (t, 4H), 2.33 (s, 3H), 1.91 (quintet, 2H). Description 31 25 7-(4-Methylpiperazin-l-yl)-l-trifluoroacetyI-l,2,3,4-tetrahydroquinoIine To a stirred solution of 7-(4-methylpiperazin-l-yl)-l,2,3,4-tetrahydroquinohne (D30, l.Og, 4 3 mmole) in CH2C12 (30ml), cooled in ice, under argon, was added tnfluoroacetic anhydride (0.67ml, 4.8 mmole) dropwise. After 30 min at 0°C the mixture was warmed to room temperature over 30 min, then washed with dilute NaHC03 (aq). The CH2C12 30 was separated, dried (Na2S04) and concentrated in vacuo to afford the title compound as a viscous yellow oil (1.42g, 100%). 'H NMR (250 MHz, CDC13) 8 (ppm): 7.26 (d, 1H), 7.06 (d, 1H), 6.78 (dd, 1H), 3 81 (t, 2H), 3.25 (t, 4H), 2.72 (br s, 6H), 2.45 (s, 3H), 2.05 (quintet, 2H). -26- Printed from Mimosa WO 98/50358 PCT/EP98/02262 Description 32 6-Bromo-7-(4-methylpiperazin-l-yl)-l-trifluoroacetyl-l,2,3,4-tetrahydroquinoline The title compound was prepared from 7-(4-methylpiperazin-l-yl)-l-tnfluoroacetyl-5 1,2,3,4-tetrahydroquinolme (D31) using a similar procedure to Descnption 14 'H NMR (250 MHz, CDC13) 6 (ppm) 7.39 (s, 1H), 7.26 (s, 1H), 3.82 (t, 2H), 3 29 (br s, 4H), 2.99 (br s, 4H), 2 82 (br s, 2H), 2.62 (s, 3H), 2.05 (quintet, 2H). Description 33 10 6-Bromo-7-(4-methylpiperazin-l-yl)-l,2,3,4-tetrahydroquinoIine To a stirred solution of 6-bromo-7-(4-methylpiperazin-l-yl)-l-tnfluoroacetyl-l,2,3,4-tetrahydroquinoline (D32, 0 74g, 1.8 mmole) in MeOH (30ml) was added K2C03 (s) (0.50g, 3.6 mmole) After 18h at room temperature the MeOH was removed in vacuo and the residue partitioned between CH2C12 and 10% Na2C03 (aq). The CH2C12 was 15 separated, dned (Na2S04) and concentrated in vacuo to afford the title compound as a yellow/brown solid (0 55g, 98%) 'H NMR (250 MHz, CDC13) 5 (ppm): 7.10 (s, 1H), 6.19 (s, 1H), 3.85 (br s, 1H), 3.26 (m, 2H), 2.99 (br s, 4H), 2 67 (t, 2H), 2.59 (br s, 4H), 2 35 (s, 3H), 1.89 (quintet, 2H). 20 Description 34 l-ButyryI-2,3-dihydro-6-nitro-lH-indoie 2,3-Dihydro-6-mtro-lH-indole (16.4g, 100 mmole) in CH2C12 (200ml) was treated with butyryl chlonde (10.6g, 100 mmole) and Et3N (lO.lg, 100 mmole) with continuous stirnng at room temperature for 2h. The reaction was then washed successively with 5N 25 HCl and saturated aqueous K2C03 solution. The reaction was then dried (Na2S04) and concentrated in vacuo to a gum which crystallised from petrol as needles to give the title compound (23.4g, 100%) 'H NMR (250 MHz, CDC13) 5 (ppm): 9 0 (s, 1H), 7.85 (dd, 1H), 7.25 (d, 1H), 4.15 (t, 2H), 3 3 (t, 2H), 2.4 (t, 2H), 1.8 (q, 2H), 1.0 (t, 3H). 30 Description 35 6-Amino-2,3-dihydro-l-butyryl-l-H-indole -27- Printed from Mimosa WO 98/50358 PCT/EP98/02262 l-Butyryl-2,3-Dihydro-6-mtro-l H-mdole (D34, 19 8g, 84.4 mmole) was stirred with 10% palladium on charcoal (2g) m MeOH (200ml) under an atmosphere of hydrogen at 50psi at such a rate that the temperature rose to 60°C and the uptake of hydrogen ceased. The reaction was then filtered through celite and the celite washed with hot MeOH to ensure 5 that no product was retained. The filtrate was evaporated in vacuo to give the title compound (13.3g, 77%) as needles. 'H NMR (250 MHz, CDC13) 8 (ppm): 7.5 (s, 1H), 6.85 (d, 1H), 6.2 (dd, 1H), 4.9 (s, 2H), 4.0 (t, 2H), 2.9 (t, 2H), 2.4 (t, 2H), 1 6 (q, 2H), 0 95 (t, 3H) 10 Description 36 1 -Butyryl-2,3-dihydro-6-iodo-l H-indole A stirred solution of 6-amino-l-butyryl-2,3-dihydro-lH-indole (D35, 3.0g, 0 015mole) in a mixture of conc. H2SO4 (3ml) and water (35ml) at 0°C was treated dropwise (tip of the addition funnel touching the liquid surface) with a solution of sodium nitrite (l.lg, 15 0 016mole) m water (10ml) whilst maintaining the temperature below 5°C This mixture was then stirred for a further 20 min at <3°C before adding it dropwise to a solution of potassium iodide (2.66g, 0.016mole) m water (10ml) at 0°C. Slight effervescence was seen and a dark orange suspension formed. The mixture was stirred for a further 1.5h while allowing to warm to room temperature. The product was extracted with EtOAc 20 (3x), the organics washed (Na2S203 solution) and dned (Na2S04) to give, on evaporation, the title compound as an orange solid (3.3g, 70%) JH NMR (250 MHz,CDC13) 8(ppm): 8.64 (s, 1H), 7.32 (dd, 1H), 6.90 (d, 1H), 4.04 (t, 2H), 3.13 (t, 2H), 2 39 (t, 2H), 1.75 (m, 2H), 1.02 (t, 3H) 25 Description 37 l-Butyryl-2,3-dihydro-6-(pyridin-4-yl)-lH-indole A suspension of l-butyryl-2,3-dihydro-6-iodo-lH-indole (D36, 3.28g, 10.4mmole) in dimethoxyethane (120ml) and water (30ml) containing Na2C03 (3 85g, 36.4mmole) was flushed with argon for lh. To the mixture was added 4-pyridylboronic acid (1.3g, 30 10.8mmole) and tetrakis(tnphenylphosphme)palladium(0) (600mg, 0.52mmole) and the mixture heated at reflux for lh. The mixture was allowed to cool, evaporated in vacuo and the residue partitioned between water and CH2CI2. The aqueous was extracted further with CH2Cl2 (2x), the organics combined and dned (Na2S04)to giye on evaporation a -28- Printed from Mimosa WO 98/50358 PCT/EP98/02262 dark brown oil, which was purified by flash chromatography (eluant 5% MeOH/CH2Cl2) to give the title compound as a brown solid (1.5g, 54%) !h NMR (250 MHz,CDC13) 8(ppm)- 8 61 (m, 3H), 7.53 (d, 2H), 7 29 (m, 2H), 4 13 (t, 2H), 3 25 (t, 2H), 2.44 (t, 2H), 1.79 (m, 2H), 1.04 (t, 3H). 5 Description 38 1 -Butyryl-2,3-dihydro-6-(l -methylpiperidin-4-yl)-H-indole To a solution of l-butyryl-2,3-dihydro-6-(pyndin-4-yl)-l H-mdole (D37, 1.5g, 5 63mmole) m acetone (50ml) was added lodomethane (1.6g, 11.3mmole) and the 10 mixture left to stand overnight. Filtration gave an orange solid (1.2g) which was dissolved m ethanol (25ml) and water (25ml) and the solution cooled to 0°C. To the solution was added sodium borohydnde (166mg, 4.4mmole) portionwise over 5 min. and the mixture stirred for a further 10 mm. To the mixture was added 2M NaOH solution (16ml) and water (40ml) and the product extracted with CH2CI2 (2x), dned (Na2SC>4) an^ 15 evaporated in vacuo to a brown oil (l.Og). The oil was then dissolved in ethanol (50ml) and hydrogenated over 10% Pd-C (lOOmg) at 50 psi and 50°C for 72h. Filtration and evaporation of the filtrate in vacuo gave the title compound as a white solid (71 Omg, 44%). *H NMR (250 MHz,CDCl3) 5(ppm): 8.19 (s, 1H), 7.11 (d, 1H), 6 88 (d, 1H), 4.04 (t, 20 2H), 3.15 (t, 2H), 2.96 (br d, 2H), 2.48 (m, 1H), 2.39 (t, 2H), 2 31 (s, 3H), 2.03 (m, 2H), 1.82 (m, 6H), 1 02 (t, 3H). Description 39 5-Bromo-2,3-dihydro-6-(l-methylpiperidin-4-yl)-lH-indole 25 To a stirred solution of l-butyryl-2,3-dihydro-6-(l-methylpiperidin-4-yl)-lH-indole (D38, 2 32mmole) in acetic acid (20ml) was added N-bromosuccinimide(454mg, 2.55mmole) and the mixture stirred at room temperature overnight The mixture was diluted with water and basified with solid K2CO3. Extraction with CH2C12, drying (Na2S04) of the organics and evaporation in vacuo gave an off-white solid (890mg). A portion of the solid 30 (790mg, 2 16mmole) in ethanol (20ml) and 2M NaOH solution (30ml) was heated at 80°C under argon for 72h. The product was extracted with CH2CI2, the organics dned (Na2S04) evaporated in vacuo to give the title compound as an orange solid (647mg, 100%). -29- Prxnted from Mimosa WO 98/50358 PCT/EP98/02262 !h NMR (250 MHz,CDC13) 8(ppm): 7 24 (s, 1H), 6.57 (s, 1H), 3.55 (t, 2H), 2 99 (m, 4H), 2.88 (m, 1H), 2 33 (s, 3H), 2 10 (m, 2H), 1 75 (m, 4H). NH not observed Description 40 5 4-(/-Butoxycarbonylamino)aniline To a stirred solution of phenylenediarmne (2 Og, 18.5mmole) m CH2CI2 (50ml) at 0°C was added dwert-butyl dicarbonate (4 25ml, 18 5mmole) and the mixture stirred whilst warming to room temperature for 16h Evaporation in vacuo gave the title compound in 80% purity, with the di-Boc compound making up the remainder (3.79g, 98%). 10 !h NMR (of title compound) (250 MHz,CDCl3) 8(ppm): 7.13 (d, 2H), 6 63 (d, 2H), 6.27 (br s, 1H), 3 50 (br s, 2H), 1.50 (s, 9H) Description 41 4-(Pyrimidin-2-yl)benzoic acid 15 The title compoimd was prepared from 4-carboxyphenylboronic acid and 2- bromopyrimidme in a similar manner to Descnption 2, obtained as a pale buff powder (35%). :H NMR (250 MHz, d6DMSO) 8 (ppm): 12.95 (s, 1H), 8.87 (d, 2H), 8.41 (d, 2H), 8.00 (d, 2H), 7.41 (t, 1H). 20 Description 42 4-(Pyrimidin-2-yI)phenyl isocyanate The title compound was prepared from 4-(pynmidin-2-yl)benzoic acid (D41) in a similar manner to Descnption 1, obtained as a pale yellow powder (83%). 25 ('H NMR - not recorded due to insolubility in CDC13). Description 43 5-Chloro-2,3-dihydro-l-(4-iodophenylaminocarbonyi)-6-(4-methylpiperazin-l-yl)-lH-indole 30 The title compound was prepared from 5-chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-lH-mdole (D13) and 4-iodoaniline in a similar mannner to Example 4, obtained as an off-white powder (54%). -30- Printed from Mimosa WO 98/50358 PCT/EP98/02262 'H NMR (250 MHz, CDC13) 8 (ppm): 7.79 (s, 1H), 7.60 (d, 2H), 7.23 (d, 2H), 7 15 (s, 1H), 6 37 (s, 1H), 4 07 (t, 2H), 3.18 (t, 2H), 3.10 (br s, 4H), 2.61 (br s, 4H), 2 36 (s, 3H) Description 44 5 N-[4-(Pyridin-4-yI)naphth-l-yl]acetamide To a solution of 4-(pyridm-4-yl)naphth-1 -ylamine (D2, 1.5g, 6.8mmole) m CH2G2 and tnethylamine (1 0ml, 7 lmmole) at 0°C was added dropwise a solution of acetyl chloride (0 5ml, 7 Ommole) in CH2C12 (10ml) and the mixture stirred whilst allowing to warm to room temperature for lh. The solution was washed with aqueous 10% Na2CC>3, the 10 organics dned (Na2SC>4) and evaporated in vacuo to give the title compound as a yellow solid (1.9g, 100%). lH NMR (250 MHz,CDCl3) 8(ppm): 8.73 (d, 2H), 7.99-7 40 (m, 8H), 2.37 (s, 3H). NH not observed 15 Description 45 N-[4-(l-Methyl-l,2,5,6-tetrahydropyridin-4-yl)naphth-l-yl)acetamide To a solution of N-[4-(pyridin-4-yl)naphth-l-yl]acetamide (D44,1 8g, 6.8mmole) m acetone (50ml) was added lodomethane (1.92g, 13.6mmole) and the mixture left to stand overnight Filtration gave a yellow solid (1.2g) which was dissolved in ethanol (25ml) 20 and water (25ml), cooled to 0°C and treated portionwise with sodium borohydnde (166mg, 4.4mmole) over 5min and then stirred for lh. To the mixture was added aqueous 10% NaOH (16ml) and water (40ml), the product extracted with CH2Cl2, dned (Na2S04) and evaporated in vacuo to give the title compound as a brown solid (880mg, 44%). 25 !h NMR (250 MHz,CDCl3) 8(ppm): 8.06 (dd, 1H), 7.86 (dd, 1H), 7.73 (d, 1H), 7.53 (m, 2H), 7.30 (s, 1H), 5.74 (m, 1H), 3.18 (br d, 2H), 2.75 (t, 2H), 2,56 (m, 2H), 2,47 (s, 3H), 2 32 (s, 3H) NH not observed Description 46 30 4-(l-Methylpiperidin-4-yI)naphth-l-ylamine A solution of N-[4-(l-methyl-l,2,5,6-tetrahydropyndm-4-yl)naphth-l-yl]acetamide (D45, 800mg, 2.9mmole) in ethanol (50ml) was hydrogenated over 10% Pd-C at 50psi and 50°C for 192h Filtration through celite and evaporation of the filtrate gave, on -31 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 evaporation, a white solid (683mg). The solid was dissolved in ethanol (10ml) and aqueous 2M NaOH (16ml) and heated at reflux under argon for 72h The mixture was extracted with CH2CI2, the organics dned (Na2S04) and evaporated in vacuo to give the title compound as an orange oil (520mg, 76%). 5 !h NMR (250 MHz,CDC13) 8(ppm). 8 06 (dd, 1H), 7 87 (dd, 1H), 7.53-7.40 (m, 2H), 7 22 (d, 1H), 6.78 (d, 1H), 4.06 (br s, 2H), 3 19 (m, 1H), 3 04 (br d, 2H), 2.36 (s, 3H), 2.20 (m, 2H), l 92 (m, 4H). Description 47 10 4-(4- AminophenyI)-2-methyloxazole A mixture of 2-methyl-4-(4-nitrophenyl)oxazole (1 70g, 8.2 mmole, J Het Chem 1981, 18, 885) and 10% palladium on carbon (0 20g) in THF (70ml) was stirred under hydrogen at atmospheric pressure for 42h. The mixture was filtered and concentrated to dryness in vacuo The residue was purified by chromatography on silica gel elutmg with 2% MeOH 15 inCH2Cl2 The title compound was obtained as a yellow powder (0.92g). 'H NMR (250 MHz, CDC13) 5 (ppm). 7.66 (s, 1H), 7.52 (d, 2H), 6 70 (d, 2H), 3 73 (s, 2H), 2.49 (s, 3H). Description 48 20 4-(2-Methyl-pyridin-4-yl)benzoic acid The title compound was prepared from 4-bromo-2-methylpyridine (J Org. Chem. 1985, 50, 4410) and 4-carboxyphenylboronic acid using a similar procedure to Descnption 2 as a white solid (84%) 'H NMR (250 MHz, d6DMSO) 8 (ppm). 8.52 (d, 1H), 8.03 (d, 2H), 7 80 (d, 2H), 7.61 (s, 25 1H), 7.52 (dd, 1H), 2.55 (s, 3H). COOH not observed. Description 49 4-(2-Methyl-pyridin-4-yl)aniline The title compound was prepared from 4-(2-methyl-pyridin-4-yl)benzoic acid (D48) 30 using a similar procedure to Description 1 to form the isocyanate, then by base hydrolysis using NaOH, to afford the amine as a beige solid (31%). 'H NMR (250 MHz, CDC13) 8 (ppm). 8.46 (d, 1H), 7.52 - 7 45 (m, 2H), 7 31 (s, 1H), 7.29 - 7.24 (m, 1H), 6.80 - 6.73 (m, 2H), 3.87 (s, 2H), 2.59 (s, 3H) -32- Pnnted from Mimosa WO 98/50358 PCT/EP98/02262 Description 50 N-(tert-Butyloxycarbonyl)-4-iodoaniline To a solution of 4-iodoaniline (3g, 0.014 mole) m dry dichloromethane (20ml) was added 5 di-tert-butyl dicarbonate (2 99g, 0.014 mole) followed by a catalytic amount of 4- dimethylaminopyridine. The reaction was stirred overnight at ambient temperature then washed with water (2x20ml) and dned (MgS04). Filtration and evaporation gave an off-white solid (1 90g, 43%). 'H NMR (250MHz, CDC13) 5 (ppm) 7.57 (d, 2H), 7.14 (d, 2H), 6.43 (br, 1H), 1 51(s, 10 9H). Description 51 N-(tert-ButyloxycarbonyI)-4-(thiazoI-2-yl)aniIine A mixture of N-(rerZ-butyloxycarbonyl)-4-iodoaniline (D50, 319mg, 1 mmole), bis 15 (pinacolato)diboron (279mg, 1.1 mmole), l,r-bis(diphenylphosphmo)ferrocene dichloropalladium (II) complex with DCM (1:1) (24mg, 0.029 mmole) and potassium acetate (294mg, 3 mmole) in dry DMF (6ml) was heated at 80°C for 2h. After cooling 2-bromothiazole (328mg, 2 mmole), 2M sodium carbonate (2.5ml) and 1,1 '-bis (diphenylphosphino)ferrocene dichloropalladium (II) complex with DCM (11) (24mg, 20 0.029 mmole) was added and the reaction heated at 80°C for 18h After cooling the solution was diluted with water (20ml). Extraction using ethyl acetate (2x20ml) followed by drying (MgS04), filtration and evaporation under reduced pressure gave an oil This was chromatographed on silica gel eluting with 10% ethyl acetate in hexane to afford the title compound as an oil (137mg, 50%) 25 'H NMR (250MHz, CDC13) 8 (ppm) 7.91 (d, 2H), 7.82 (d, 1H), 7.48 (d, 2H), 7.27 (d, 1H), 6.62 (br, 1H), 1.54 (s, 9H). Description 52 4-(Thiazol-2-yl)aniline 30 A solution of N-(/ert-butyloxycarbonyl)-4-(thiazol-2-yl)anilme (D51, 122mg, 0.44 mmole) in dichloromethane (2ml) and trifluoroacetic acid (0.1ml) was stirred at ambient temperature for 18h and then water (20ml) was added The aqueous phase was extracted with dichloromethane (2x10ml) and the extract washed with 10% aqueous sodium -33 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 hydrogen carbonate (2x20ml), then dned (MgS04) and evaporated under reduced pressure to give a light yellow oil, which solidified on standing (70mg, 90%). 'H NMR (250MHz, CDC13) 8 (ppm) 7 76 (m, 3H), 7.20 (d, 1H), 6 72 (d, 2H), 3 90 (br s, 2H). 5 Description 53 4-(lsoquinolin-2-yl)benzoic acid The title compound was prepared from 4-carboxyphenylboromc acid and 4-bromoisoquinohne using a similar procedure to Descnption 2, obtained as an off-white 10 solid (58%) 'H NMR (250MHz, d6DMSO) 8 (ppm). 13.15 (br s, 1H), 9.39 (s, 1H), 8 49 (s, 1H), 8 25 (d, 1H), 8 13 (d, 2H), 7 90 - 7.67 (m, 5H). Description 54 15 4-(Isoquinolin-4-yl)pbenyI isocyanate The title compound was prepared from 4-(isoquinolin-4-yl)benzoic acid (D53) using a similar procedure to Descnption 1 The isocyanate was used as its toluene solution without concentration to the neat compound. 20 Description 55 4-(Quinolin-3-yl)benzoic acid The title compound was prepared from 4-carboxyphenylboromc acid and 3-bromoquinoline using a similar procedure to Descnption 2, obtained as a white solid (72%). 25 'H NMR (250MHz, d^MSO) 8 (ppm): 13.09 (br s, 1H), 9.32 (d, 1H), 8.76 (d, 1H), 8.07 (m, 5H), 7,83 (m, 2H), 7.67 (m, 1H). Description 56 4-(Quinolin-3-yl)phenyl isocyanate 30 The title compound was prepared from 4-(quinolin-3-yl)benzoic acid (D55) using a similar procedure to Description 51. The isocyanate was used as its toluene solution without concentration to the neat compound. -34- Pnnted from Mimosa WO 98/50358 PCT/EP98/02262 Description 57 4-(Quinoiin-8-yl)benzoic acid The title compound was prepared from 4-carboxyphenylboromc acid and 8-bromoqumoline using a similar procedure to Description 2, obtained as a white 5 solid (65%). 'H NMR (250MHz, d6DMSO) 6 (ppm): 12.98 (br s, 1H), 8.92 (m, 1H), 8.46 (d, 1H), 8.06 (m, 3H), 7 80 (m, 4H), 7.60 (m, 1H). Description 58 10 4-(Quinolin-8-yl)phenyl isocyanate The title compound was prepared from 4-(quinolin-8-yl)benzoic acid (D57) using a similar procedure to Description 51 The isocyanate was used as its toluene solution without concentration to the neat compound 15 Description 59 3-Bromo-2,6-dimethylpyridine (D59a) and 4-Bromo-2,6-dimethylpyridine (D59b) A stirred solution of phosphorus oxybromide (25g, 0.085 mole) in 1,2-dichloroethane (250ml) at room temperature under argon was treated with 2,6-20 lutidme-N-oxide (lOg, 0.081mole), then heated at reflux for 6h. The mixture was allowed to cool, then poured slowly into well stirred ice/water (400ml) and basified by addition of solid K2C03. The aqueous mixture was extracted with dichloromethane and the extract dried (Na2S04) and concentrated under vacuum The residue was chromatographed on silica gel elutmg with 1:1 ether /60-80 petrol 25 to separate four components. The second component was 3-bromo-2,6-dimethylpyridine (2.5g, 21%) as a yellow oil; 'H NMR (250MHz, CDC13) 8 (ppm): 7.66 (d, 1H), 6.86 (d, 1H), 2.63 (s, 3H), 2.48 (s, 3H) and the third component was 4-bromo-2,6-dimethylpyridine (1.5g, 12%) as a pale 30 yellow oil 'H NMR (250MHz, CDC13) 8 (ppm). 7.16 (s, 2H), 2.50 (s, 6H) Description 60 -35- Pnnted from Mimosa WO 98/50358 PCT/EP98/02262 4-(2,6-Dimethyl-py ridin-4-yl)b enzoic acid The title compound was prepared from 4-bromo-2,6-dimethylpyndine (D59b) and 4-carboxyphenylboromc acid using a similar procedure to Descnption 2 as a white solid (76%) 5 'H NMR (250MHz, d6DMSO) 8 (ppm): 8.05 (d, 2H), 7 86 (d, 2H), 7.42 (s, 2H), 2 50 (s, 6H). Acid proton not observed Description 61 4-(2,6-Dimethyl-pyridin-3-yl)benzoic acid 10 The title compound was prepared from 3-bromo-2,6-dimethylpyndine (D59a) and 4-carboxyphenylboromc acid using a similar procedure to Descnption 2 as a beige solid (76%). 'H NMR (250MHz, d6 DMSO) 8 (ppm) 8.00 (d, 2H), 7.52 (d, 1H), 7.42 (d, 2H), 7.18 (d, 1H), 2 47 (s, 3H), 2 40 (s, 3H). Acid proton not observed 15 Description 62 4-(2,6-DimethyI-pyridin-4-yI)phenyl isocyanate The title compound was prepared from 4-(2,6-dimethyl-pyndin-4-yl)benzoic acid (D60) using a similar procedure to Descnption 1. The isocyanate was used as its 20 toluene solution without concentration to the neat compound Description 63 4-(2,6-Dimethyl-pyridin-3-yl)phenyl isocy an ate The title compound was prepared from 4-(2,6-dimethyl-pyridin-3-yl)benzoic acid 25 (D61) using a similar procedure to Descnption 1 The isocyanate was used as its toluene solution without concentration to the neat compound. Description 64 8-Bromo-5-nitroquinoline 30 8-Bromoquinohne (1 5g, 7.2 mmole) was added dropwise to a well stirred solution of conc. H2S04 (5ml), conc. HN03 (10ml) and fuming HN03 (2ml), cooled in ice The mixture was heated at 65°C for 30h, then cooled and poured into H20 (350ml) with stirring The precipitate that formed was filtered, washed -36- Printed from Mimosa WO 98/50358 PCT/EP98/02262 with H20 and dned under vacuum to give the title compound as a pale cream solid (1.10g, 60%) 'H NMR (250MHz, CDC13) 8 (ppm): 9 17 (dd, 1H), 9 07 (dd, 1H), 8.26 (d, 1H), 8 20 (d, 1H), 7.74 (dd, 1H) 5 Description 65 5-Nitro-8-phenyIquinoIine The title compound was prepared from 8-bromo-5-nitroquinoline (D64) and phenylboronic acid using a similar procedure to Description 2, as an orange/brown 10 solid (99%) 'H NMR (250MHz, CDC13) 8 (ppm). 9.11 - 9.05 (m, 2H), 8 44 (d, 1H), 7.82 (d, 1H), 7.70 - 7 63 (m, 3H), 7.59 - 7.46 (m, 3H). Description 66 15 5-Amino-8-phenylquinoIine The title compound was prepared from 5-nitro-8-phenylquinoline (D65) using a similar procedure to Description 20, as an orange/brown solid (97%). *H NMR (250MHz, CDC13) 8 (ppm): 8.93 (dd, 1H), 8.21 (dd, 1H), 7.76 (dd, 1H), 7 66 (d, 1H), 7 59 - 7.32 (m, 5H), 6.89 (d, 1H), 4 23 (s, 2H) 20 Description 67 6-Acetamido-2-methylquinoline The title compound was prepared from 6-amino-2-methylquinoline and acetic anhydnde using a similar procedure to Description 8, as a green solid (95%). 25 'H NMR (250MHz, CDC13) 8 (ppm): 8.30 (d, 1H), 8.01 (d, 1H), 7.95 (d, 1H), 7 49 (m, 2H), 7.27 (d, 1H), 2.72 (s, 3H), 2.25 (s, 3H). Description 68 6-Amino-2-(2-phenylethenyl)quinoline 30 A suspension of 6-acetamido-2-methylquinoline (D67, 600mg, 3 0 mmole) in acetic anhydride (6ml) was treated with benzaldehyde (954mg, 9.0 mmole) and the mixture heated at 120°C for 40h, then cooled and the acetic anhydride removed in vacuo The residue was dissolved in 2M NaOH (30ml) and EtOH -37- Printed from Mimosa WO 98/50358 PCT/EP98/02262 (10ml) and heated under reflux with stimng After 18h the EtOH was removed in vacuo and the residue extracted with EtOAc (3x100ml) The organics were combined, dried (Na2S04) and concentrated in vacuo giving a crude brown oil, which was punfied by chromatography on basic alumina eluting with EtOAc 5 The title compound was obtained as a brown solid (210mg, 28%), partially contaminated with benzyl alcohol. *H NMR (250MHz, CDC13) 8 (ppm): 7.91 - 7.87 (m, 2H), 7.60 - 7.56 (m, 2H), 7.54 (d, 1H), 7.42 - 7.28 (m, 5H), 7.15 (dd, 1H), 6 89 (d, 1H), 3.96 (s, 2H) 10 Description 69 6-Amino-2-(2-phenyIethyl)quinoline The title compound was prepared from 6-amino-2-(2-phenylethenyl)qumohne (D68) using a similar procedure to Description 20, as a yellow oil (41%), partially contaminated with benzyl alcohol 15 'H NMR (250MHz, CDC13) 8 (ppm): 7.87 (d, 1H), 7 80 (d, 1H), 7 38 - 7.08 (m, 7H), 6.89 (d, 1H), 3.90 (s, 2H), 3.25 - 3.07 (m, 4H). Description 70 2-(3-Nitrophenoxy)pyrimidine 20 A stirred mixture of 3-mtrophenol (2 08g, 15 mmole), 2-bomopynmidine (2.38g, 15 mmole) and anhydrous potassium carbonate (2.76g, 20 mmole) in dry DMF (20ml) was heated at 80°C for 4h. The cooled mixture was concentrated to dryness in vacuo and the residue partitioned between CH2C12 (75ml) and water (50ml) The organic phase was separated, washed with water, dned (Na2S04) and 25 concentrated to dryness in vacuo. The residue was punfied by chromatography on silica gel eluting with CH2C12. The title compound was isolated as a pale yellow powder (1.94g, 60%). lH NMR (250MHz, CDC13) 8 (ppm): 8.60 (d, 2H), 8.14 (m, 2H), 7.58 (m, 2H), 7 12 (t, 1H) 30 Description 71 3-(Pyrimidin-2-yIoxy)aniline -38- Printed from Mimosa WO 98/50358 PCT/EP98/02262 To a stirred mixture of 2-(3-mtrophenoxy)pynmidine (D70, 0 65g, 3 mmole) and tin (II) chloride (2.28g, 12 mmole) in methanol (30ml) was added conc HCl (0.7ml) The mixture was heated at reflux for 2h, cooled and concentrated in vacuo to near dryness The residue was treated with CH2C12 (50ml) and water 5 (25ml) and 2N NaOH solution was added to adjust the pH to 12 The mixture was filtered and the organic phase separated, washed with water, dried (Na2S04) and concentrated to dryness in vacuo to afford the title compound as a yellow powder (0.50g, 89%) 'H NMR (250MHz, CDC13) 5 (ppm). 8.55 (d, 2H), 7.19 (t, 1H), 7.02 (t, 1H), 6 59 10 - 6.51 (m, 3H), 3 76 (s, 2H) Description 72 N-Methyl-4-nitro-N-(pyrimidin-2-yl)aniline To a stirred solution of N-methyl-4-nitroaniline (2 20g, 14.5 mmole) in dry DMF 15 (25ml) was added potassium tert-butoxide (1 79g, 16 mmole). After stirring for lh at room temperature 2-bromopynmidme (2.30g, 14 5 mmole) was added and the mixture warmed to 80°C for 6h and then stood overnight at room temperature. After concentrating to dryness in vacuo, the residue was partitioned between CH2C12 (100ml) and water (30ml) The organic phase was washed with water, 20 dned (Na2S04) and concentrated to dryness. Trituration of the residue in diethyl ether afforded the title compound as a pale yellow-orange powder (1.24g, 37%) 'H NMR (250MHz, CDC13) 8 (ppm): 8.43 (d, 2H), 8 25 (d, 2H), 7 56 (d, 2H), 6.77 (t, 1H), 3.67 (s, 3H). 25 Description 73 4-[N-Methyl-N-(pyrimidin-2-yl)amino]aniline A solution of N-methyl-4-nitro-N-(pynmidin-2-yl)amline (D72,1 30g, 5.6 mmole) m methanol (70ml) and ethyl acetate (70ml) was treated with 10% palladium on carbon (0.25g), and shaken under hydrogen at 1 atmosphere for 48h 30 The filtered mixture was concentrated to dryness and the residue tnturated in diethyl ether to afford the title compound as a pale orange-brown powder (0 78g, 68%) -39- Prmted from Mimosa WO 98/50358 PCT/EP98/02262 "H NMR (250MHz, CDC13) 5 (ppm): 8.30 (d, 2H), 7 07 (d, 2H), 6 68 (d, 2H), 6.48 (t, 1H), 3 66 (br s, 2H), 3.45 (s, 3H) Description 74 5 5-(Pyridin-4-yl)naphth-l -ylamine The title compound was prepared from 5-bromo-l-naphthylamme (JP 08151353A2) and 4-pyndylboronic acid using a similar procedure to Descnption 2. *H NMR (250MHz,CDC13) 5(ppm) 8 75-8 67 (m, 2H), 7 93 (d, 1H), 7 70-7.35 (m, 4H), 7 28-7.20 (m, 2H), 6 85-6.80 (m, 1H), 4.25 (s, 2H). 10 Description 75 N-[5-(Pyridin-4-yl)naphth-l-yl]acetamide The title compound was prepared from 5-(pyridin-4-yl)naphth-l-ylamme (D74) m a similar manner to Descnption 44. MH+263. 15 Description 76 N-[5-(l-MethyI-l,2,5,6-tetrahydropyridin-4-yl)naphth-l-yl]acetamide The title compoimd was prepared from N-[5-(pyridin-4-yl)naphth-l-yl]acetamide (D75) in a similar manner to Description 45. MH+ 281. 20 Description 77 5-(l-Methylpiperidin-4-yl)naphth-l-ylamine The title compound was prepared from N-[5-(l-methyl-l,2,5,6-tetrahydropyndin-4-yl)-naphth-l-yl]acetamide (D76) in a similar manner to Descnption 46 25 *H NMR (250MHz,CDCI3) 8(ppm):7.72 (m, 1H), 7.57 (d, 1H), 7 42 (m, 2H), 7 32 (t, 1H), 6.78 (d, 1H), 4.16 (br s, 2H), 3 28 (m, 1H), 3.05 (br d, 2H), 2 37 (s, 3H), 2.20 (m, 2H), 1.93 (m,4H). Description 78 30 N-2-(4-Nitrophenyl)ethy]-trifluoroacetamide A solution of tnfluoroacetic anhydnde (10.6ml) m dichloromethane (100ml) was added dropwise to a stirred solution of 2,6-lutidme (17.4ml) and 4-nitrophenethylamine hydrochloride (15 2g, 75 mmole) at 0°C. The mixture was -40- Printed from Mimosa WO 98/50358 PCT/EP98/02262 stirred at 25°C overnight under argon and then washed with dilute citric acid (x2), brine and dried (Na2S04). The material in the organic phase gave the title compound as a pale yellow solid (19.04g). 5 Description 79 7-Nitro-l,2,3,4-tetrahydro-2-trifluoroacetylisoquinoline N-2-(4-Nitrophenyl)ethyl-trifluoroacetamide (D78,2 26g, 9.15 mmole) and paraformaldehyde (0 45g, 14 4 mmole) in acetic acid (10ml) and conc H2SO4 (15ml) were stirred at 25°C for 20h according to the procedure of G E Stokker, 10 Tet. Lett., 1996, 37, 5453. Work-up afforded the title compound as a white solid (2.17g) lH NMR (250MHz, CDCI3) 8 (ppm). 8 10 (m, 2H,), 7.38 (t, 1H), 4 92-4.85 (2 x s, 2H), 3 92 (m, 2H), 3.10 (m, 2H). MH+ 274. 15 Description 80 7-Nitro-l,2,3,4-tetrahydroisoquinoline 7-Nitro-l,2,3,4-tetrahydro-2-trifluoroacetylisoquinoline (D79, 17.2g; 63 mmole) was hydrolysed at room temperature using a solution of potassium carbonate (46.6g) m 10% aqueous methanol (660ml). Work-up with dichloromethane gave 20 the title compound (11 g). Description 81 2-MethyI-7-nitro-l,2,3,4-tetrahydroisoquinoline 7-Nitro-l,2,3,4-tetrahydroisoquinoline (D80, 2.08g; 11.7 mmole) was treated with 25 88% formic acid (3.45ml) and 37% aqueous formaldehyde (5.88ml) at 80°C for 2h according to the procedure of G.M. Carrera and D.S. Garvey, J. Het. Chem., 1992, 29, 847. Basification with 10% sodium hydroxide followed by extraction with ethyl acetate afforded an orange gum (2.3g) Chromatography on silica gel in 0-3% methanol/ethyl acetate gave the title compound as an orange solid (1 7g) 30 MH+193. Description 82 7-Amino-2-methyI-l,2,3,4-tetrahydroisoquinoline -41 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 2-Methyl-7-nitro-l,2,3,4-tetrahydroisoqumoline (D81, 0.25g, 1.3 mmole) in methanol (40ml) was hydrogenated over 10% palladium on carbon (lOOmg) at atmospheric pressure overnight. The catalyst was removed by filtration through a pad of kieselguhr and evaporation in vacuo gave the title compound as a white 5 solid (213mg) MH+163 Description 83 8-Bromoquinoline-2,4-dicarboxylic acid To a stirred solution of KOH (21.3g, 0.38 mole) in H2O (64ml) was added 7-bromoisatin 10 (lOg, 0 044 mole, Proc. Royal Soc , 1958,148,481) over 1 min, followed by pyruvic acid (5.35ml, 0 077 mole) over 1 mm The resultant solution was stirred at room temperature for lh, then heated under reflux for 1.5h, then cooled to room temperature, diluted with H2O (100ml) and filtered. The filtrate was acidified to pHl with conc. HCl acid, filtered, and the solid washed with H2O and dried under vacuum The title compound was a 15 brown solid (10 1 g, 77%). *H NMR (250 MHz, d6 DMSO) 8(ppm) • 8.92 (dd, 1H), 8 64 (s, 1H), 8 44 (dd, 1H), 7 86 (t, 1H) Acid protons not observed. Description 84 20 8-BromoquinoIine-4-carboxylic acid A solution of 8-bromoquinolme-2,4-dicarboxylic acid (D83, lOg, 34 mmole) m nitrobenzene (40ml) was heated under reflux for 2h, then allowed to cool to room temperature, diluted with hexane (60ml) and the title compound filtered off as a brown solid (8.5g, 100%) 25 *H NMR (250 MHz, d6 DMSO) 5(ppm) : 8.95 (d, 1H), 8.50 (dd, 1H), 8 04 (dd, 1H), 7.82 (d, 1H), 7.44 (t, 1H). Acid proton not observed. Description 85 8-Phenylquinoline-4-carboxylic acid 30 The title compound was prepared from 8-bromoquinoline-4-carboxylic acid (D 84) and phenylboronic acid using a similar procedure to Description 2, as a brown solid (63%). *H NMR (250 MHz, CDCI3) 8 (ppm): 9.12 (d, 1H), 8.89 (dd, 1H), 8.05 (d, 1H), 7 84-7.73 (m,2H), 7.68-7 64 (m, 2H), 7.54-7.40 (m, 3H). Acid proton not discernible. -42- Printed from Mimosa WO 98/50358 PCT/EP98/02262 Description 86 8-Phenylquinolin-4-yl isocyanate The title compound was prepared from 8-phenylquinoline-4-carboxylic acid (D 85) using 5 a similar procedure to Description 1. The isocyanate was used as its toluene soloution without concentration to the neat compound Description 87 4-Amino-2-methylphenylboronic acid 10 A stirred solution of 4-bromo-3-methylanihne (20g, 0.107 mole) and tnethylamme (33ml, 0.237 mole) in dichloromethane (250ml) at 0°C under argon was treated dropwise over 15 min with a solution of bis(chlorodimethylsilyl)ethane (25.3g, 0.12 mole) in dichloromethane (100ml). The mixture was warmed to room temperature and stirred for 20h, then filtered and concentrated in vacuo The residue was extracted with 60-80 petrol 15 (400ml) and the filtrate concentrated in vacuo to leave the stabase as an orange oil (35g, 100%). This was dissolved in dry THF (400ml), coled to -65°C under argon and treated dropwise over 15 min with 2.5M n-butyllithium m hexane (52ml, 0.13mole). The mixture was stirred at -65°C for lh, then treated dropwise over 10 min with tnisopropylborate (30ml, 0.13 mole), stirred at -65°C for a further 1 5h, then treated with 20 saturated aqueous NH4C1 solution (100ml) and allowed to warm to room temperature The mixture was diluted with water (200ml), acidified with conc. HCl acid (50ml), stirred for 20 mm, then concentrated under vacuum to approx. 400ml volume. The aqueous residue was washed with ethyl acetate and then basified by addition of solid K2C03. The basic mixture was extracted with ethyl acetate and the extract dned (Na2S04) and 25 concentrated under vacuum to approx. 150ml volume, when a solid began to precipitate out. The mixture was cooled to 8°C and the solid filtered off and dned to afford the title compound as a white solid (9.2g, 51%). 'H NMR (250MHz, d6DMSO) 8 (ppm)- 7.69 (d, 1H), 6.40-6.32 (m, 2H), 5.34 (br s, 2H), 2.52 (s, 3H). Acid protons not observed. 30 Description 88 4-(2,6-Dimethyl-pyridin-4-yI)-3-methylaniline -43- Printed from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 4-chloro-2,6-dimethylpyndme (Chem. Abs 1952, 46, 4541) and 4-amino-2-methylphenylboromc acid (D87) using a similar procedure to Descnption 2 as beige solid (4%) 'H NMR (250MHz, CDC13) 8 (ppm). 7.01 (d, 1H), 6.90 (s, 2H), 6.62-6 54 (m, 2H), 3 70 5 (br s, 2H), 2 55 (s, 6H), 2.22 (s, 3H) Description 89 3-Methyl-4-(6-methyl-pyridin-2-yI)aniline The title compound was prepared from 2-bromo-6-methylpyridine and 4-amino-2-10 methylphenylboronic acid (D87) using a similar procedure to Description 2 as beige solid (100%) 'H NMR (250MHz, CDC13) 8 (ppm)- 7.62-7.55 (m, 1H), 7.22 (d, 1H), 7.15 (d, 1H), 7 05 (d, 1H), 6 62-6 55 (m, 2H), 3.68 (br s, 2H), 2.59 (s, 3H), 2.31 (s, 3H). 15 Description 90 5-Carboxy-naphth-l-ylboronic acid A stirred solution of 5-bromo-l-naphthoic acid (Bull. Soc Chim Fr., 1968, 7, 2957, 22 3g, 0 089 mole) m dry THF (1000ml) at -60°C under argon was treated dropwise over 15 mm with 1.6M n-butyllithium in hexane (125ml, 0.20 mole). The initial brown 20 solution gave a beige precipitate as the first equivalent was added, which redissolved on addition of the second equivalent. The resulting solution was stirred at -60°C for 40 min, then tnisopropylborate (51ml, 0.22 mole) was added, and the mixture stirred at -60°C for a further lh, before warming gradually to -10°C. Saturated aqueous NH4C1 solution was added (300ml), followed by water (400ml) and then 5M HCl acid (200ml) The resulting 25 mixture was concentrated in vacuo to approx. 1000ml volume, then basified by addition of 40% NaOH solution and washed with ethyl acetate. The aqueous was added to excess 5M HCl acid and the solid which precipitated out was filtered off, washed with water and dned to afford a white solid (9 67g), which contained approx 50% of the title compound together with 1-naphthoic acid. 30 Description 91 5-(6-Methy 1-py ridin-2-yl)-l -naphthoic acid -44- Printed from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 2-bromo-6-methylpyridine and 5-carboxy-naphth-1-ylboronic acid (D90) using a similar procedure to Description 2 as beige solid (46%) 'H NMR (250MHz, d6DMSO) 5 (ppm). 8.90 (d, 1H), 8.13 (d, 1H), 8 06 (dd, 1H), 7.84 (t, 1H), 7.67 (t, 1H), 7.62-7.46 (m, 2H), 7 41 (d, 1H), 7.32 (d, 1H), 2.55 (s, 3H). Acid proton 5 not observed. Description 92 5-(6-Methyl-pyridin-2-yl)naphth-l-yl isocyanate The title compound was prepared from 5-(6-methyl-pyndin-2-yl)-l-naphthoic acid (D91) 10 using a similar procedure to Description 1. The isocyanate was not isolated, but used in the next step as its toluene solution. Description 93 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-trifluoroacetyl-lH-indole 15 The title compoimd was prepared from 5-chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-lH-indole (D13) using a similar procedure to Descnption 31, as a beige solid (96%). *H NMR (250 MHz, CDC13) 5 (ppm). 8.02 (s, 1H), 7 25 (s, 1 H), 4.29 (t, 2H), 3.19 (t, 2H), 3 10 (br s, 4H), 2 64 (br s, 4H), 2.39 (s, 3H). 20 Description 94 5-Chloro-2,3-dihydro-6-(piperazin-l-yl)-l-trifluoroacetyl-lH-indole To a stirred soloution of 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)tnfluoroacetyl-lH-indole (D93, 7.0g, 20 mmole) in 1,2-dichloroethane (200ml) under argon, was added diisopropylethylamine (3.50ml, 20 mmole) followed by 1-chloroethyl chloroformate 25 (4.35ml, 40mmole) After lh the mixture was washed with dilute NaHC03 (aq), then dried (Na2SC>4) and concentrated in vacuo giving a brown solid (8.86g, 100%). A suspension in MeOH (200ml) was stirred under reflux for 3h, then allowed to cool and the MeOH removed in vacuo The residue was partitioned between dilute NaHC03 (aq) and CH2CI2. The CH2CI2 was seperated and the aqueous reextracted with CH2CI2 (2 x 30 50ml). The organics were combined, dried (Na2S04) and concentrated in vacuo giving the title compound as a brown solid (4.79g, 72%). !H NMR (250 MHz, CDCI3) 5 (ppm) : 8.00 (s, 1H), 7.25 (s, 1H), 4.30 (t, 2H), 3.20 (t, 2H), 3 10-3.08 (br m, 8 H). NH not disernible. -45- Printed from Mimosa WO 98/50358 PCT/EP98/02262 Description 95 6-(4-Acetylpiperazm-l-yl)-5-chloro-2,3-dihydro-l-trifluoroacetyl-lH-indole A stirred soloution of 5-chloro-2,3-dihydro-6-(piperazm-l-yl)-l-trifluoroacetyl-lH-indole 5 (D 94, 1,0g, 3.0 mmole) in CH2CI2 (50ml) cooled in ice, was treated with acetic anhydride (0.34g, 3.3 mmole) then allowed to warm to room temperature After 6h the mixture was washed with dilute NaHCC>3 (aq), dried (Na2SC>4) and concentrated in vacuo to afford the title compound as a brown solid (1 lOg, 97%) lH NMR (250 MHz, CDCI3) 8 (ppm): 7.98 (s, 1H), 7 26 (s, 1H), 4 31 (t, 2H), 3.79 (br s, 10 2H), 3 64 (br s, 2H), 3 21 (t, 2H), 3 05-3.00 (m, 4H), 2.15 (s, 3H) Description 96 6-(4-Acetylpiperazin-l-yI)-5-chIoro-2,3-dihydro-lH-indole The title compound was prepared from 6-(4-acetylpiperazm-l-yl)-5-chloro-2,3-dihydro-l-15 trifluoroacetyl-lH-indole (D 95) using a similar procedure to Descnption 33, as a brown foam (81%). !h NMR (250 MHz, CDCI3) 6 (ppm). 7.09 (s, 1H), 6 33 (s, 1H), 3 79-3.75 (m, 2H), 3.63-3.54 (m,4H), 3 01-2 91 (m, 6H), 2 13 (s, 3H). NH not discernible 20 Description 97 5-Chloro-2,3-dihydro-6-(4-ethylpiperazin-l-yl)-lH-indole A stirred solution of 6-(4-acetylpiperazin-l-yl)-5-chloro-2,3-dihydro-lH-mdole (D96, 0.65g, 2.3 mmole) in THF (30ml) at room temperature under argon was treated with 1M borane-THF complex in THF (9.3ml, 9.3 mmole), then heated at reflux for 5h. The 25 mixture was cooled to 0°C then treated dropwise with conc HCl acid (6ml) in methanol (25ml). After 30 min, the solution was heated to reflux for 2h, then concentrated in vacuo The residue was treated with ethyl acetate (50ml) and 2M HCl acid (40ml), shaken well and the aqueous layer separated, basified with K2C03 and extracted with dichloromethane. The extract was dned (Na2S04), concentrated in vacuo and the residue 30 purified by chromatography on silica gel eluting with 2-10% methanol/dichloroemethane to afford the title compound as a beige solid (0.3 lg, 50%). *H NMR (250MHz, CDCI3) 8 (ppm)- 7.07 (s, 1H), 6.41 (s, 1H), 3 73 (br s, 1H), 3 56 (t, 2H), 3.03 (br s, 4H), 2.97 (t, 2H), 2.63 (br s, 4H), 2.49 (q, 2H), 1.13 (t, 3H) -46- Printed from Mimosa WO 98/50358 PCT/EP98/02262 Description 98 6-[4-(terf-Butyloxycarbonyl)piperazin-l-yl]-5-chloro-2,3-dihydro-l-trifluoroacetyl-IH-indole 5 The title compound was prepared from 5-chloro-2,3-dihydro-6-(piperazm-1 -yl)-1 - tnfluoroacetyl-1 H-indole (D94) and di-iert-butyl dicarbonate using a similar procedure to Description 95, as a brown foam (100%) lH NMR (250MHz, CDC13) 5 (ppm): 7 99 (s, 1H), 7 26 (s, 1H), 4 30 (t, 2H), 3 60 (t, 4H), 3 20 (t, 2H), 2 98 (t, 4H), 1.49 (s, 9H) 10 Description 99 6- [4-(tert-ButyIoxycarbonyl)piperazin-1 -yl]-5-chloro-2,3-dihydro-l H-indole The title compound was prepared from 6-[4-(/er/-butyloxycarbonyl)piperazm-1 -yl]-5-chloro-2,3-dihydro-l-tnfluoroacetyl-lH-indole (D98) using a similar procedure to 15 Descnption 33, as a brown solid (84%). !h NMR (250MHz, CDCI3) 8 (ppm). 7.08 (s, 1H), 6.35 (s, 1H), 3.60 - 3.53 (m, 6H), 3 01 - 2.89 (m, 6H), 1 48 (s, 9H), NH not discernible. Description 100 20 6-[4-(tert-ButyIoxycarbonyI)piperazin-l-yl]-5-chloro-2,3-dihydro-l-[4-(pyridin-4-yl)naphth-l-ylaminocarbonyl]-lH-indole The title compound was prepared from 4-(pyndin-4-yl)naphth-l-ylamine (D2) and 6-[4-(rer/-butyloxycarbonyl)piperazin-l-yl]-5-chloro-2,3-dihydroindole (D99) using a similar procedure to Example 4, as a yellow/brown solid (67%). 25 !h NMR (250MHz, CDCI3) 8 (ppm). 8.74 (d, 2H), 7.99 (d, 1H), 7.91 - 7.86 (m, 3H), 7.67 - 7.41 (m, 5H), 7 21 (s, 1H), 6.81 (s, 1H), 4.31 (t, 2H), 3.56 (t, 4H), 3.30 (t, 2H), 2.96 (t, 4H), 1 46 (s, 9H). Description 101 30 6-[4-(/<?rt-Butyloxycarbonyl)piperazin-l-yl]-5-chIoro-2,3-dihydro-l-[5-(pyridin-4-yl)n aphth-1 -ylaminocarbonyl]-1 H-indole -47- Printed from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 5-(pyndin-4-yl)naphth-l-ylamine (D74) and 6-[4-(rer/-butyloxycarbonyl)piperazin-l-yl]-5-chloro-2,3-dihydro-l H-mdole (D99) using a similar procedure to Example 4, as a yellow/brown solid (74%). *H NMR (250MHz, CDCI3) 5 (ppm): 8 75 (d, 2H), 8 02 (d, 1H), 7.85 (s, 1H), 7.78 - 7 42 5 (m, 7H), 7.21 (s, 1H), 6.74 (s, 1H), 4.30 (t, 2H), 3.56 (t, 4H), 3.30 (t, 2H), 2.95 (t, 4H), 1.45 (s, 9H). Description 102 4-(Pyridazin-3-yl)benzoic acid 10 The title compound was prepared from 3-chloropyndazme and 4-carboxyphenylboronic acid using a similar procedure to Description 24 as a brown solid (87%) MS: m/z =199 (M-H) Description 103 15 4-(Pyrazin-2-yl)benzoic acid The title compound was prepared from 2-chloropyrazine and 4-carboxyphenylboronic acid using a similar procedure to Description 24 as a white solid (88%). MS: m/z = 156 (M-C02). 20 Description 104 6-Phenylnicotinic acid The title compound was prepared from 6-chloromcotinic acid and phenylboronic acid using a similar procedure to Description 24 as an off white solid (54%). MS: m/z = 200 (MH+) 25 Description 105 4-(6-Methyl-pyridazin-3-yl)benzoic acid The title compound was prepared from 3-chloro-6-methylpyndazine and 4-carboxyphenylboronic acid using a similar procedure to Descnption 24 as a yellow solid 30 (52%). MS: m/z = 213 (M-H). Description 106 4-(4-Cyano-3-methylphenyl)benzoic acid -48- Printed from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 4-bromo-2-methylbenzonitrile and 4-carboxyphenylboronic acid using a similar procedure to Description 24 as a white sohd (75%). MS: m/z = 236 (M-H). 5 Description 107 4-(5-Methyl-oxazol-2-yI)aniline A mixture of 5-methyl-2-(4-nitrophenyl)oxazole (Chim. Ther 1973, 8(4), 437) (3 Og, 15mmole) and 10% palladium on carbon (0 25g) in THF (75ml) was stirred under an atmosphere of hydrogen for 24h. The mixture was filtered and concentrated in vacuo to 10 dryness to afford the title compound as a pale buff powder (2.29g, 89%). !H NMR (250 MHz, d6DMSO) 8 (ppm) 7.70 (d, 2H), 7.15 (s, 1H), 6 73 (d, 2H), 5 74 (s, 2H), 2.42 (s, 3H). Description 108 15 5-Nitro-naphth-l-ylcarboxamide A stirred suspension of 5-nitro-naphth-l-ylcarboxylic acid (Chem Pharm Bull 1984, 32(10), 3968) (3.50g, 16mmole) in CH2C12 (200ml) was treated with oxalyl chloride (2 1 ml, 24 mmole) and DMF (2 drops) The mixture was stirred at room temperature for 5h The solution was concentrated to dryness in vacuo, and the residue dissolved in dry THF 20 (200ml). Ammonia was slowly bubbled through the solution for 0.5h. The mixture was concentrated to dryness in vacuo and the residue tnturated in water, and the solid filtered off and dned in vacuo to afford the title compound as a pale brown powder (3.34g, 95%) 'H NMR (250 MHz, d6DMSO) 8(ppm): 8.47 (d, 1H), 8.23-8.13 (m, 2H), 8.05 (s, 1H) 7.71-7.59 (m, 4H) 25 Description 109 N-[l-(Dimethylamino)ethylidene]-5-nitronaphth-l-yIcarboxamide A stirred mixture of 5-nitro-naphth-l-ylcarboxamide (D108,1.50g, 7 mmole) and N,N-dimethylacetamide dimethylacetal (3ml) was heated to 110°C for 2 h. The cooled 30 mixture was diluted with water (20ml) and the precipitated solid filtered off, washed with water and dried in vacuo to afford the title compound as a pale brown powder (1,60g, 80%). - 49 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 'H NMR (250 MHz, CDC13) 8 (ppm): 9.31 (d, 1H), 8 53 (d, 1H), 8 22 (dd, 1H) 8.15 (dd, 1H), 7.72-7.56 (m, 2H), 3.19 (d, 6H), 2.45 (s, 3H). Description 110 5 3-Methyl-5-(5-nitro-naphth-l-yI)-l,2,4-oxadiazoIe To a stirred solution of hydroxylamine hydrochloride (0 47g, 6.75 mmole) and 5M NaOH solution (1 35 ml, 6.75 mmole) m 70% aqueous acetic acid (10 ml) was added N-[l-(dimethylamino)ethylidene]-5-nitronaphth-l-ylcarboxamide (D109, 1 55g, 5 4 mmole) The mixture was warmed to 80°C for 4h, then cooled and diluted with water (50ml) The 10 precipitated solid was filitered off, washed with water and dned in vacuo to leave the title compound as a pale buff powder (1.11 g, 80%). 'H NMR (250 MHz, CDC13) 8 (ppm): 9.52 (d, 1H), 8 71 (d, 1H), 8.44 (dd, 1H) 8 25 (dd, 1H), 7 87-7.73 (m, 2H), 2.59 (s, 3H). 15 Description 111 5-(3-Methyl-l,2,4-oxadiazol-5-yI)naphth-l-ylamine The title compound was prepared from 3-methyl-5-(5-nitronaphth-l-yl)-l,2,4-oxadiazole (D110) using a similar procedure to Descnption 71 as a pale yellow powder (54%) 'H NMR (250 MHz CDC13) 8 (ppm) 8 52 (d, 1H), 8.30 (dd, 1H), 8.09 (d, 1H), 7.58-7 44 20 (m, 2H), 6 88 (dd, 1H), 4 23 (s, 2H) 2.56 (s, 3H). Description 112 5-Nitro-N-propargylnaphth-l-ylcarboxamide A stirred suspension of 5-nitronaphth-l-ylcarboxylic acid (Chem. Pharm Bull. 1984, 25 32(10), 3986) (1 lOg, 5 mmole) in CH2C12 (50ml) was treated with oxalyl chlonde (0.5 ml, 6 mmole) and DMF (1 drop). After 3h at room temperature the mixture was concentrated to dryness in vacuo. The residue was dissolved m CH2C12 (30ml), treated with tnethylamme (1.4nl, 10 mmole) followed with dropwise addition of a solution of propargylamme (0 28g, 5 mmole) in CH2C12 (10ml) After stimng at room temperature 30 for 18h the mixture was washed with water, dned (Na2S04) and concentrated to dryness in vacuo The residue was tnturated in diethyl ether to afford the title compound as a pale yellow powder (0.79g, 61%). -50- Printed from Mimosa WO 98/50358 PCT/EP98/02262 'H NMR (250 MHz, CDC13) 8 (ppm): 8.62 (t, 2H), 8.24 (d, 1H), 7.73-7 59 (m, 3H), 6 30 (s, 1H) 4 34 (dd, 2H), 2.33 (t, 1H) Description 113 5 5-Methyl-2-(5-nitronaphth-l -yl)oxazole A stirred mixture of 5-mtro-N-propargylnaphth-l-ylcarboxamide (D112, 0 75g, 3 mmole) and mercuric acetate (0.04g, 0.12 mmole) in glacial acetic acid (10 ml) was heated to reflux for 4h. The cooled mixture was concentrated to dryness in vacuo, and the residue dissolved m CH2C12, washed with aq. K2C03 solution, dried (Na2S04) and concentrated 10 to dryness in vacuo. The residue was subjected to flash chromatography on silica gel eluting with CH2C12 to afford the title compound as a yellow powder (0 50g, 66%) 'H NMR (250 MHz, CDC13) 8 (ppm)- 9.75 (d, 1H), 8.54 (d, 1H), 8.26 (d, 1H), 8 19 (d, 1H), 7 79-7.64 (m, 2H), 7.01 (s, 1H), 2 47 (s, 3H). 15 Description 114 5-(5-Methyloxazol-2-yl)naphth-l-ylamine The title compound was prepared from 5-methyl-2-(5-nitronaphth-l-yl)oxazole (D113) using a similar procedure to Descnption 28, obtained as a yellow/green gum (95%). 'H NMR (250 MHz, d6DMSO) 8 (ppm)- 8 64 (d, 1H), 8.11 (dd, 1H), 7 94 (d, 1H), 7.53-20 7 39 (m, 2H), 6.97 (d, 1H), 6.48 (d, 1H), 4.18 (s, 2H), 2 45 (s, 3H). Description 115 3-MethyI-4-(pyrimidin-2-yl)aniline The title compound was prepared from 2-bromopynmidine and 4-amino-2-methylphenyl 25 boromc acid (D87) using a similar procedure to Descnpton 2 as yellow solid (46%). 'H NMR (250 MHz, CDC13) 8 (ppm): 8.76 (d, 2H), 7.75 (d, 1H), 7.11 (t, 1H), 6 62 (d, 1H), 6.59 (s, 1H), 3.78 (br, 2H), 2.55 (s, 3H). Description 116 30 3-Methyl-4-(pyrimidin-5-yl)anilin e The title compound was prepared from 5-bromopyrimidine and 4-amino-2-methylphenylboronic acid (D87) using a similar procedure to Descnption 2 as a straw coloured sohd (91%). -51 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 'H NMR (250 MHz, CDC13) 5 (ppm): 9.14 (s, 1H), 8 70 (s, 2H), 7 67 (m, 1H), 7 01 (d, 1H), 6 65 (s, 1H), 6.62 (d, 1H), 3 60 (br, 2H), 2.23 (s, 3H) Description 117 5 2,6-Dimethyl-4-iodopyridine A sirred solution of 4-chloro-2,6-dimethylpyridine (Chem. Abs. 1952,46,4541) (2.6g, 18 mmole) in 2-butanone (250ml) was treated with sodium iodide (17 6g, 120 mmole) and 4-toluenesulphonic acid (3.4g, 18 mmole) and the mixture heated at reflux under argon for 72h. The reaction mixture was cooled, then concentrated in vacuo and the residue was 10 treated with water (200ml) and extracted with ethyl acetate The extract was washed with aqueous sodium thiosulphate solution, then dned (Na2S04) and concentrated in vacuo to afford the title compound as a white solid, which was converted to its hydrochloride salt as a white solid from acetone (3.44g, 69%). 'H NMR (free base) (250 MHz, CDC13) 8 (ppm): 7.37 (s, 2H), 2 46 (s, 6H). MH+ = 234 15 Description 118 5-(2,6-Dimethyi-pyridin-4-yl)-l -naphthoic acid The title compound was prepared from 2,6-dimethyl-4-iodopyridme (D117) and 5-carboxynaphth-l-ylboromc acid (D90) using a similar procedure to Descnption 2 as a 20 white solid (70%). 'H NMR (250 MHz, d6DMSO) 8 (ppm): 8 75 (d, 1H), 7.99 (dd, 1H), 7 80 (d, 1H), 7 60-7 52 (m, 1H), 7.50-7.32 (m, 2H), 7.00 (s, 2H), 2 36 (s, 6H). Acid proton not observed Description 119 25 5-(2,6-Dimethyl-pyridin-4-yl)naphth-l-yl isocyanate The title compound was prepared from 5-(2,6-dimethyl-pyridin-4-yl)-l-naphthoic acid (D118) using a similar procedure to Descnption 1. The isocyanate was not isolated, but used as its toluene solution in the next step. 30 Description 120 4-(2,6-Dimethylpyridin-3yl)-3-methylaniline -52- Printed from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 3-bromo-2,6-dimethylpyndine (D59a) and 4-amino-2-methylphenylboromc acid (D87) using a similar procedure to Descnption 2 as a pale yellow oil (6.5%). 'H NMR (250 MHz, CDC13) 8 (ppm): 7.32-7.25 (m, 1H), 7.00 (d, 1H), 6 87 (d, 1H), 6.65-5 6.52 (m, 2H), 3 67 (br s, 2H), 2.56 (s, 3H), 2.28 (s, 3H), 1.98 (s, 3H). Description 121 3-Methyl-4-(thiazoI-2-yl)aniline The title compound was prepared from 2-bromothiazole and 4-amino-2-10 methylphenylboronic acid (D87) using a similar procedure to Description 2 as a yellow/brown oil (65%). 'H NMR (400 MHz, CDC13) 8 (ppm)- 7.83 (d, 1H), 7.57 (d, 1H), 7 28 (m, 1H), 6 57 (m, 2H), 3.80 (br, 2H), 2.53 (s, 3H). 15 Description 122 5-(Pyrimidin-5-yl)-l-naphthoic acid The title compound was prepared from 5-bromopyrimidine and 5-carboxynaphth-l-ylboronic acid (D90) using a similar procedure to Descnption 2 as a beige solid (78%). lH NMR (250 MHz, d6DMSO) 8 (ppm) 13.30 (br, 1H), 9.35 (s, 1H), 9.00 (s, 2H), 8.96 20 (d, 1H), 8.19 (d, 1H), 7 93 (d, 1H), 7.78 (m, 1H),7 65 (m, 2H). Description 123 5-(Pyrimidin-5-yl)naphth-l-yl isocyanate The title compound was prepared from 5-(pyrimidm-5-yl)-l-naphthoic acid (D122) using 25 a similar procedure to Decsription 1. The isocyanate was not isolated, but used as its toluene solution in the next step. Description 124 5-Acetylnaphth-l-ylamine 30 A stirred solution of l-acetyl-5-nitronaphthalene (Aust. J. Chem 1995, 48(12), 1969) (0.75g, 3 5 mmole), 10% Pd-C (0.20g) and cyclohexene (10 ml) in methanol (75 ml) was heated under reflux for 6h. The cooled mixture was filtered and concentrated in vacuo. The residue was dissolved in CH2CI2 (50 ml), washed with water, dned (Na2S04) and -53- Printed from Mimosa WO 98/50358 PCT/EP98/02262 concentrated to dryness. Tnturation of the residue with ether/hexane afforded the title compound as a yellow/brown powder (0,52g, 80%). 'H NMR (250 MHz, CDC13) 8 (ppm): 8.03 (t, 2H), 7.83 (dd, 1H), 7.49-7 36 (m, 2H), 6.83 (d, 1H), 4.17 (s, 2H), 2.73 (s, 3H). 5 Description 125 5-(Pyrimidin-2-yloxy)naphth-l-ylamme The title compound was prepared from 5-hydroxynaphth-l-ylamme and 2-bromopynmidine using a similar procedure to Descnption 70, as a pale buff coloured 10 powder (58%). 5H NMR (250 MHz, CDC13) 8 (ppm): 8 52 (d, 2H), 7.73 (d, 1H), 7 48 (t, 1H), 7.40-7 21 (m, 3H), 7.01 (t, 1H), 6.78 (d, 1H), 4.13 (s, 2H). Description 126 15 5-Cyanonaphth-l-ylamine To a stirred suspension of 5-nitronaphth-l-ylcarbonitrile (D128, 0.15g, 0.76 mmole) in ethanol (10ml) and water (5ml) was added iron powder (0.2lg, 3.7 mmole) and ammonium chlonde (0.02g, 0.4 mmole), then the mixture was heated under reflux for 0.5h. The mixture was cooled slightly, filtered and concentrated in vacuo. The residue 20 was partitioned between ethyl acetate (25ml) and water (15ml). The organic layer was separated, dried (Na2SC>4) and concentrated to dryness to afford the title compound as a yellow/green powder (O.llg, 85%). 'H NMR (250 MHz, CDC13) 8 (ppm): 8.06 (d, 1H), 7 88 (d, 1H), 7.68 (d, 1H), 7.49 (m, 2H), 6.88 (d, 1H), 4.27 (s, 2H). 25 Description 127 5-Nitronaphth-l-ylcarbonitrile To stirred solution of 5-nitronaphth-l-ylcarboxamide (D108,0.20g, 0.93mmole) m CH2CI2 (10ml) was added 2.5M solution of trimethylsilylphosphate m CH2C12 (5ml) 30 (Synthesis, 1982, 591) and the mixture heated to reflux for 2h. The cooled mixture was treated with water (10ml) and after stimng for 10 min the organic phase was separated, washed with bnne, dried (Na2S04) and concentrated to dryness in vacuo. The residue -54- Printed from Mimosa WO 98/50358 PCT/EP98/02262 was subjected to flash chromatography on silica gel eluting with CH2CI2 to afford the title compound as a colourless powder (0.12g, 66%) 'H NMR (250 MHz, CDC13) 5 (ppm): 8.82 (d, 1H), 8.57 (d, 1H), 8 35 (d, 1H), 8.06 (d, 1H), 7.83 (m, 2H) 5 Description 128 5-Nitronaphth-l -ylamidoxime To a solution of sodium hydroxide (0.71g, 17.8mmole) in methanol (100ml) was added hydroxylamine hydrochloride (1 23g, 1.78mmole). The mixture was treated with 5-10 nitronaphth-l-ylcarbonitrile (D127, 1.60g, 8.1mmole) and heated to reflux for 48h The cooled mixture was concentrated by evaporation to 10ml and then treated with water (50ml) The precipitate was collected, washed with water and dried in vacuo to afford the title compound as a pale yellow powder (1 65g, 88%) 'H NMR (250 MHz, d6DMSO) 5 (ppm). 9.74 (s, 1H), 8.66 (d, 1H), 8.30 (m, 2H), 7.86-15 7.72 (m,3H), 6.14 (s,2H). Description 129 5-Methyl-3-(5-nitronaphth-l-yl)-l,2,4-oxadiazole To a stirred solution of 5-mtronaphth-l-ylamidoxime (D128, 1.28g, 5.5mmole) in 20 pyridine (10ml) was added dropwise acetyl chlonde (0.78ml, 11 mmole). The mixture was stirred at room temperature for 0.5h, then heated to reflux for 24h The cooled mixture was treated with water (100ml) and extracted with ethyl acetate (3x25ml). The combined organic extracts were washed with dilute HCl, water, dned (Na2SC>4) and concentrated to dryness. The residue was subjected to flash chromatography on silica gel 25 eluting with CH2CI2 to afford the title compound as a pale yellow powder (0.86g, 61%) lH NMR (250 MHz, CDC13) 5 (ppm): 9.27 (d, 1H), 8.63 (d, 1H), 8.36, (dd, 1H), 8.24 (dd, 1H), 7 81 (q, 1H), 7.69 (q, 1H), 2.75 (s, 3H). Description 130 30 5-(5-Methyl-l,2,4-oxadiazoI-3-yl)naphth-l-yIamine The title compound was prepared according to the procedure outlined in Descnption 126, as brown gum. This was converted to its hydrochloride salt to afford a grey powder. -55- Printed from Mimosa WO 98/50358 PCT/EP98/02262 'H NMR (HCl salt) (250 MHz, CD3OD) 8 (ppm)- 8 72 (t, 1H), 8 08 (dd, 1H), 7 91 (d, 1H), 7.60 (dd, 1H), 7.44 (d, 2H), 4 63 (s, 2H), 2 46, (s, 3H). 5 Example 1 l-[(4-Bromo-3-methyIphenyl)aminocarbonyI]-5-methoxy-6-(4-methylpiperazin-l-yl)indole To a solution of 5-methoxy-6-(4-methylpiperazin-l-yl)indole (130mg, 0.50 mmole, intemediate 2 in W095/06637) in anhydrous THF (10ml) under argon, was added 10 potassium t-butoxide (59mg, 0 50 mmole) and the mixture stirred for 15 mm. To this was added a solution of 4-bromo-3-methylphenyl isocyanate (Dl, 127mg, 0.60 mmole) m anhydrous THF (10ml). The resulting mixture was stirred under argon at room temperature for 16h, then concentrated in vacuo. The residue was punfied by column chromatography on silica gel eluting with 0-6% MeOH/CH2Cl2 to afford the title 15 compound as a pale yellow solid (108mg, 45%). lH NMR (250MHz, CDC13) 8 (ppm):7 67 (s, 1H), 7.34 (d, 1H), 7.30 (d, 1H), 7.21 (d, 1H), 7.15 (s, 1H), 7.05 (dd, 1H), 6.86 (s, 1H), 6.42 (d, 1H), 3.76 (s, 3H), 3.03 (br s, 4H), 2.59 (br s, 4H), 2.25 (s, 6H). 20 Example 2 l-[(4-Bromo-3-methylphenyl)aminocarbonyl]-2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l -yl)-l H-indole 2,3-Dihydro-5-methoxy-6-(4-methylpiperzin-l-yl)-lH-indole (0.10g, 0.40 mmole, intermediate 3 in WO 95/06627) in dichloromethane (10ml) was added to a solution of 4-25 bromo-3-methylphenyl isocyanate (Dl, 0.1 lg, 0.50 mmole) in dichloromethane (10ml). The mixture was stirred at room temperature for 17h, then concentrated in vacuo to afford a dark yellow oil. This oil was stirred with diethyl ether producing the title compound as a yellow solid, which was filtered off and dried (0.17g, 92%). 'H NMR (250MHz, CDC13) 8 (ppm):7.59 (s, 1H), 7.36 (d, 1H), 7 29 (d, 1H), 7 03 (dd, 30 1H), 6.65 (s, 1H), 6.25 (s, 1H), 3.98 (t, 2H), 3.76 (s, 3H), 3.13 (t, 2H), 3.05 (br s, 4H), 2.54 (br s, 4H), 2 30 (s, 3H), 2.28 (s, 3H). Example 3 -56- Printed from Mimosa WO 98/50358 PCT/EP98/02262 l-[(2,3-Dichlorophenyl)aminocarbonyl]-2,3-dihydro-5-methoxy-6-(4-methyIpiperaziii-l-yl)-lH-indole The title compound was prepared from 2,3-dichlorophenyl isocyanate and 2,3-dihydro-5-methoxy-6-(4-methylpiperzin-l-yl)-lH-indole (intermediate 3 in W095/06627) following 5 a similar procedure to Example 2. 'H NMR (250MHz, CDC13) 6 (ppm):8.27 (dd, IH), 7.68 (s, IH), 7.23-7 13 (m, 2H), 7.15 (dd, IH), 6.75 (s, IH), 4.15 (t, 2H), 3.85 (s, 3H), 3.22 (t, 2H), 3.13 (br s, 4H), 2.63 (br s, 4H), 2 36 (s, 3H) 10 Example 4 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)naphth-l-ylaminocarbonyl]-lH-indole To a stirred solution of tnphosgene (84 mg, 0 28 mmole) m CH2CI2 (10 ml) under argon, was added to a solution of 4-(pyridin-4-yl)naphth-l-ylamme (D2, 196 mg, 0 89 mmole) 15 and NEt3 (90 mg, 0 89 mmole) in CH2Cl2 (10 ml) dropwise over 30 mm. After the addition was complete, the mixture was stirred at room temperature for 15 min, then a solution of 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-IH-indole (intermediate 3 in W095/06627, 200 mg, 0.81 mmole) in CH2CI2 (10 ml) was added. After 6h the mixture was washed with 10% Na2C03(aq), dried (Na2SC>4) and concentrated in vacuo 20 giving a crude green oil, which was purified by chromatography on silica eluting with 2-5% MeOH/CH2Cl2. The title compound was obtained as a beige solid (292 mg, 73%) *H NMR (250 MHz, CDCI3) 8 (ppm): 8.73 (dd, 2H), 7 99 (dd, IH), 7.91 (d, IH), 7.88 (dd, IH), 7.75 (s, IH), 7.60-7.49 (m, 2H), 7.46 (d, IH), 7 42 (dd, 2H), 6.81 (s, IH), 6.77 (s, IH), 4 27 (t, 2H), 3.85 (s, 3H), 3.28 (t, 2H), 3.11 (br s, 4H), 2.60 (br s, 4H), 2.34 (s, 25 3H) Example 5 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l-[5-(4-pyridyl)naphth-l-ylaminocarbonyl]-l H-indole 30 The title compound was prepared from 5-(pyridin-4-yl)naphth-l-yl isocyanate (D4) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole (intermediate 3 m W095/06627) using a similar procedure to Example 2. -57- Pnnted from Mimosa WO 98/50358 PCT/EP98/02262 lH NMR (250 MHz, CDCI3) 5 (ppm): 8.72 (d, 2H), 8.02 (d, IH), 7.74 (s, IH), 7 72 (d, IH), 7.66 (d, IH), 7 55 (t, IH), 7.41-7.46 (m, 2H), 7.40 (d, 2H), 6.85 (s, IH), 6 75 (s, IH), 4.21 (t, 2H), 3 84 (s, 3H), 3 24 (t, 2H), 3.07 (brs, 4H), 2.56 (br s, 4H), 2.31 (s, 3H) 5 Example 6 l-[2,3-Dichloro-4-(pyridin-4-yl)phenylaminocarbonyl]-2,3-dihydro-5-methoxy-6-(4-methylpiper azin-1 -y 1)-1 H-indole The title compound was prepared from 2,3-dichloro-4-(pyridin-4-yl)amhne (D7) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole (intermediate 3 in WO 10 95/06627) using a similar procedure to Example 4 as an orange/brown solid (54%) *H NMR (250 MHz, CDCI3) 8 (ppm): 8.67 (d, 2H), 8.41 (d, IH), 7.70 (s, IH), 7 36 (d, 2H), 7.27 (s, IH), 7.26 (d, IH), 6.76 (s, IH), 4.18 (t, 2H), 3.85 (s, 3H), 3.24 (t, 2H), 3 18 (br s, 4H), 2 71 (br s, 4H), 2.41 (s, 3H). 15 Example 7 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yI)-l-(quinolin-5-ylaminocarbonyl)-1 H-indole The title compound was prepared from 5-aminoquinoline and 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole (intermediate 3 in W095/06627) using a similar 20 procedure to Example 4. !H NMR (250 MHz, CDCI3) 8 (ppm): 8.92 (dd, IH), 8.27 (dd, IH), 7.99 (t, IH), 7 69-7.71 (m, 3H), 7.41 (dd, IH), 6 75 (s, IH), 6.70 (s, IH), 4.20 (t, 2H), 3 85 (s, 3H), 3 25 (t, 2H), 3.09 (br s, 4H), 2.59 (br s, 4H), 2.32 (s, 3H). 25 Example 8 2,3-Dihydro-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)naphth-l-ylaminocarbonyl]-l H-indole The title compound was prepared from 4-(pyridin-4-yl)naphth-l-ylamine (D2) and 2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (Dl 1) using a similar procedure to 30 Example 4 as a beige solid (50%). JH NMR (250 MHz, CDC13) 8 (ppm): 8.75-8.70 (m, 2H), 7.99 (d, IH), 7.92-7.86 (m, 2H), 7.75 (d, IH), 7.62-7.40 (m, 5H), 7.09 (d, IH), 6.90 (s, IH), 6.56 (dd, IH), 4.26 (t, 2H), 3.28-3 17 (m, 6H), 2.55-2.50 (m, 4H), 2.32 (s, 3H). -58- Printed from Mimosa WO 98/50358 PCT/EP98/02262 Example 9 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)naphth-l-ylaminocarbonyl]-lH-indole 5 The title compound was prepared from 4-(pyridin-4-yl)naphth-l-ylamine (D2) and 5-chloro-2,3-dihydro-6-(4-methylpiperazm-l-yl)-lH-indole (D13) using a similar procedure to Example 4 (38%). This was converted to its hydrochloride salt as a yellow sohd from acetone *H NMR (free base) (250 MHz, CDCI3) 8 (ppm): 8 73-8.67 (m, 2H), 8.00 (dd, IH), 10 7 91-7.82 (m, 3H), 7.62-7.37 (m, 5H), 7.18 (s, IH), 6.92 (s, IH), 4.26 (t, 2H), 3.24 (t, 2H), 3.06 (br s, 4H), 2.56 (br s, 4H), 2.32 (s, 3H). Example 10 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)naphth-l-15 y laminocarbony 1]-1 H-indole The title compound was prepared from 2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyndm-4-yl)naphth-l-ylaminocarbonyl]-lH-mdole (E8) and benzyltnmethylammonium tnbromide using a similar procedure Description 14 as a beige solid (86%). This matenal was converted to its hydrochloride salt as a yellow solid from acetone 20 *H NMR (250 MHz, CDCI3) 8 (ppm): 8.76-8.70 (m, 2H), 8.00 (d, IH), 7 91-7.82 (m, 3H), 7.62-7.34 (m, 6H), 6.93 (s, IH), 4.26 (t, 2H), 3 24 (t, 2H), 3.05 (br s, 4H), 2.56 (br s, 4H), 2.32 (s, 3H). Example 11 25 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)phenylaminocarbonyl]-lH-indole The title compound was prepared from 4-(pyridin-4-yl)aniline (D5) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l H-indole (D15) using a similar procedure to Example 4 as a white solid (24%). 30 ]H NMR (250 MHz, CDCI3) 8 (ppm): 8.52-8.45 (m, 2H), 8 00 (s, IH), 7.71 (s, IH), 7.60-7 45 (m, 4H), 7.37 (dd, 2H), 7.18 (s, IH), 4.05 (t, 2H), 3.03 (t, 2H), 2.92 (br s, 4H), 2 45 (br s, 4H), 2.20 (s, 3H). -59- Printed from Mimosa WO 98/50358 PCT/EP98/02262 Example 12 5-Bromo-l-[3-chloro-4-(pyridin-4-yl)phenylaminocarbonyl]-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 3-chloro-4-(pyndin-4-yl)aniline (D6) and 5-5 bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l H-indole (D15) using a similar procedure to Example 4 as a white solid (13%). !h NMR (250 MHz, CDC13 + d6DMSO) 5 (ppm): 8.75 (d, 2H), 8.40 (s, IH), 7.92 (s, IH), 7 88 (d, IH), 7 75 (dd, IH), 7.52 (s, IH), 7.42 (d, 2H), 7.33 (d, IH), 4.27 (t, 2H), 3.25 (t, 2H), 2.97 (br s, 4H), 2.60 (br s, 4H), 2.35 (s, 3H). 10 Example 13 2,3-Dihydro-5-methyl-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)naphth-l-ylaminocarbonyl]-l H-indole The title compound was prepared from 4-(pyndin-4-yl)naphth-l-ylamine (D2) and 2,3-15 dihydro-5-methyl-6-(4-methylpiperazin-l-yl)-lH-indole (D17) usmg a similar procedure to Example 4 (52%) This material was converted to its hydrochloride salt as a yellow solid from acetone. !h NMR (free base) (250 MHz, CDCI3) 8 (ppm): 8 73-8.70 (m, 2H), 7.98 (d, IH), 7.93-7.85 (m, 2H), 7.73 (s, IH), 7.60-7.48 (m, 5H), 7.02 (s, IH), 6.95 (s, IH), 4.23 (t, 2H), 20 3.22 (t, 2H), 2.95-2.90 (m, 4H), 2.54 (br s, 4H), 2.31 (s, 3H), 2.26 (s, 3H) Example 14 l-[3-Chloro-4-(pyridin-4-yl)phenylaminocarbonyl]-2,3-dihydro-5-methyl-6-(4-methylpiperazin-l -yl)-l H-indole 25 The title compound was prepared from 3-chloro-4-(pyridin-4-yl)aniline (D6) and 2,3-dihydro-5-methyl-6-(4-methylpiperazin-l-yl)-lH-indole (D17) using a similar procedure to Example 4 as a white solid (67%). NMR (250 MHz, d6DMSO) 8 (ppm). 8.92 (s, IH), 8.80 (d, 2H), 8.08 (d, IH), 7.87-7.83 (m, 2H), 7.63 (d, 2H), 7.56 (d, IH), 7.14 (s, IH), 4.27 (t, 2H), 3.24 (t, 2H), 2 94 (br s, 30 4H), 2.65 (br s, 4H), 2.38 (s, 3H), 2.32 (s, 3H). Example 15 -60- Printed from Mimosa WO 98/50358 PCT/EP98/02262 2,3-Dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yI)naphth-l-ylaminocarbonyI]-5-vinyl-lH-indole The title compound was prepared from 4-(pyridin-4-yl)naphth-l-ylamine (D2) and 2,3-dihydro-6-(4-methylpiperazm-l-yl)-5-vinyl-l H-mdole (D19) usmg a similar procedure to 5 Example 4 (50%). This material was converted to its hydrochloride salt as a yellow sohd from ethyl acetate. *H NMR (free base) (250 MHz, CDCI3) 8 (ppm): 8.77-8.70 (m, 2H), 8 00 (d, IH), 7 96-7 86 (m, 2H), 7.76 (s, IH), 7.65-7.40 (m, 5H), 7.37 (s, IH), 7.0 (dd, IH), 6 92 (s, IH), 5.60 (dd, IH), 5.15 (dd, IH), 4.28 (t, 2H), 3.29 (t, 2H), 3.05-2.95 (m, 4H), 2.55 (br s, 4H), 10 2 33 (s, 3H) Example 16 2,3-Dihydro-5-ethyl-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)naphth-l-ylaminocarbonyl]-lH-indole 15 The title compound was prepared from 4-(pyndin-4-yl)naphth-l-ylamine (D2) and 2,3-dihydro-5-ethyl-6-(4-methylpiperazm-l-yl)-lH-indole (D21) using a similar procedure to Example 4 as a beige solid (43%). This material was converted to its hydrochloride salt as a yellow solid from acetone iH NMR (free base) (250 MHz, CDCI3) 8 (ppm): 8.74-8.70 (m, 2H), 8.03-7.87 (m, 3H), 20 7.77 (s, IH), 7.60-7.38 (m, 5H), 7.09 (s, IH), 6.92 (s, IH), 4.26 (t, 2H), 3.26 (t, 2H), 2.98-2.92 (m, 4H), 2.66 (q, 2H), 2.61 (br s, 4H), 2.36 (s, 3H), 1.23 (t, 3H). Example 17 l-[3-Chloro-4-(pyridin-4-yl)phenylaminocarbonyl]-2,3-dihydro-5-ethyl-6-(4-25 methylpiperazin-l-yl)-lH-indole The title compound was prepared from 3-chloro-4-(pyridin-4-yl)amline (D6) and 2,3-dihydro-5-ethyl-6-(4-methylpiperazin-l-yl)-lH-indole (D21) using a similar procedure to Example 4 as a white solid (33%). *H NMR (250 MHz, CDCI3) 8 (ppm): 8.72-8.62 (m, 2H), 7.73-7.65 (m, 2H), 7.50-7.20 30 (m, 4H), 7 07 (s, IH), 6.60 (s, IH), 4.09 (t, 2H), 3 18 (t, 2H), 2.97-2.90 (m, 4H), 2 66 (q, 2H), 2.57 (br s, 4H), 2.35 (s, 3H), 1.22 (t, 3H). Example 18 -61 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 2,3-Dibydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)naphth-l-ylaminocarbonyl]-5-trifluoromethyl-lH-indole The title compound was prepared from 4-(pyridin-4-yl)naphth-l -ylamine (D2) and 2,3-dihydro-6-(4-methylpiperazin-l-yl)-5-trifluoromethyl-1 H-mdole (D23) using a similar 5 procedure to Example 4 as a beige solid (42%). This material was converted to its hydrochloride salt as a yellow solid from acetone *H NMR (free base) (250 MHz, CDCI3) 8 (ppm): 8.77-8.71 (m, 2H), 8 07 (s, IH), 8.01-7.85 (m, 3H), 7 63-7.39 (m, 6H), 6.94 (s, IH), 4.33 (t, 2H), 3.32 (t, 2H), 3 05-2 96 (m, 4H), 2 64 (br s, 4H), 2.38 (s, 3H). 10 Example 19 l-[3-Cbloro-4-(pyridin-4-yl)phenylaminocarbonyl]-2,3-dihydro-6-(4-methylpiperazin-l-yl)-5-trifluoromethyl-lH-indole The title compound was prepared from 3-chloro-4-(pyridin-4-yl)aniline (D6) and 2,3-15 dihydro-6-(4-methylpiperazm-l-yl)-5-tnfluoromethyl-lH-indole (D23) using a similar procedure to Example 4 as a beige solid (17%). *H NMR (250 MHz, CDCI3) 8 (ppm): 8.69-8.65 (m, 2H), 8.05 (s, IH), 7 67 (d, IH), 7 46 (dd, IH), 7.44-7.37 (m, 3H), 7.31 (d, IH), 6.59 (s, IH), 4.16 (t, 2H), 3.27 (t, 2H), 3.00-2.94 (m, 4H), 2.55 (br s, 4H), 2.34 (s, 3H). 20 Example 20 2,3-Dihydro-5-niethoxy-6-(4-methyIpiperazin-l-yl)-l-[4-(pyridin-4-yl)naphth-l-ylacetyl]-l H-indole To a stirred suspension of 4-(pyridin-4-yl)naphth-l-ylacetic acid (D24,213 mg, 0.81 25 mmole) in CH2CI2 (30 ml) was added oxalyl chloride (206 mg, 1.6 mmole) followed by DMF (1 drop). After 2h the solvents and excess oxalyl chloride were removed in vacuo to afford the acid chloride as a pale yellow solid This was dissolved in CH2CI2 (15 ml) and added portionwise over 10 min to a stirred solution of 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole (intermediate 3 in WO 95/06627,200 mg, 0.81 mmole) 30 and NEt3 (164 mg, 1.6 mmole) in CH2CI2 (15 ml) at 0°C under argon After 30 min at 0°C the mixture was stirred at room temperature for 5h, then washed with 10% Na2C03 (aq), dried (Na2S04) and concentrated in vacuo. The crude green/brown oil was purified -62- Prmted from Mimosa WO 98/50358 PCT/EP98/02262 by chromatography on silica eluting with 2-5% MeCH/CH2Cl2 to afford the title compound as a yellow solid (340 mg, 85%) *H NMR (250 MHz, CDC13) 5 (ppm): 8 72 (d, 2H), 8.02 (s, IH), 8.02 (d, IH), 7.87 (d, IH), 7.37-7.60 (m, 6H), 6.74 (s, IH), 4.26 (s, 2H), 4.25 (t, 2H), 3.85 (s, 3H), 3.22 (t, 2H), 5 3.08 (br s, 4H), 2.57 (br s, 4H), 2.32 (s, 3H). Example 21 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l-[5-(pyridin-4-yl)naphth-l-ylacetyl]-lH-indole 10 The title compound was prepared from 5-(pyridin-4-yl)naphth-l-ylacetic acid (D25) and 2,3-dihyro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole (intermediate 3 in WO 95/06627) using a similar procedure to Example 20. *H NMR (250 MHz, CDCI3) 6 (ppm). 8 72, (d, 2H), 8.03 (d, IH), 8.02 (s, IH), 7 78 (dd, IH), 7.59 (t, IH), 7.45-7.39 (m, 5H), 6.74 (s, IH), 4.25 (s, 2H), 4 22 (t, 2H), 3 84 (s, 3H), 15 3.20 (t, 2H), 3.07 (br s, 4H), 2.57 (br s, 4H), 2.31 (s, 3H) Example 22 2,3-Dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridm-4-yl)naphth-l-ylacetyl]-lH-indole 20 The title compound was prepared from 4-(pyndin-4-yl)naphth-l-ylacetic acid (D24) and 2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (Dl 1) using a similar procedure to Example 20 as a beige solid from ethyl acetate (72%). iH NMR (250 MHz, CDCI3) 8 (ppm): 8.75-8.70 (m, 2H), 8.04-7.94 (m, 2H), 7.88 (d, IH), 7.62-7.33 (m, 6H), 7.09 (d, IH), 6.61 (dd, IH), 4.26 (s, 2H), 4.25 (t, 2H), 3.25-3.13 25 (m, 6H), 2.55-2.47 (m, 4H), 2.30 (s, 3H). Example 23 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)naphth-l-ylacetyl]-lH-indole 30 The title compound was prepared from 4-(pyridin-4-yl)naphth-l-ylacetic acid (D24) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l H-indole (D13) using a similar procedure to Example 20 as a yellow oil (50%). This material was converted to its hydrochloride salt as a beige solid from ethyl acetate. -63- Printed from Mimosa WO 98/50358 PCT/EP98/02262 *H NMR (free base) (250 MHz, CDCI3) 8 (ppm): 8 75-8.70 (m, 2H), 8.08 (s, IH), 8.00 (d, IH), 7.88 (d, IH), 7.65-7.35 (m, 6H), 7 19 (s, IH), 4.27 (t+s, 4H), 3 20 (t, 2H), 3.06 (br s, 4H), 2 57 (br s, 4H), 2.33 (s, 3H). 5 Example 24 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yI)-l-[4-(pyridin-4-yl)naphtta-l-ylacetyl]-lH-indole The title compound was prepared from 2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyndin-4-yl)naphth-l-ylacetyl]-lH-indole (E22) and benzyltnmethylammomum 10 tnbromide using a similar procedure to Descnption 14 (62%). This matenal was converted to its hydrochloride salt as a white solid from ethyl acetate *H NMR (free base) (250 MHz, CDCI3) 8 (ppm) 8.75-8.70 (m, 2H), 8.08 (s, IH), 8.00 (d, IH), 7.89 (d, IH), 7.63-7 35 (m, 7H), 4.27 (t+s, 4H), 3.20 (t, 2H), 3.04 (br s, 4H), 2.56 (br s, 4H), 2.32 (s, 3H). 15 Example 25 2,3-Dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)naphth-l-ylacetyl]-5-vinyl-lH-indole The title compound was prepared from 4-(pyridin-4-yl)naphth-l-ylacetic acid (D24) and 20 2,3-dihydro-6-(4-methylpiperazin-l-yl)-5-vmyl-lH-indole (D19) using a similar procedure to Example 20 (45%). This material was converted to its hydrochloride salt as a white solid from acetone/ethyl acetate. !H NMR (free base) (250 MHz, CDCI3) 8 (ppm): 8.75-8.68 (m, 2H), 8.05-7 96 (m, 2H), 7.88 (d, IH), 7.65-7.30 (m, 7H), 7 00 (dd, IH), 5.60 (dd, IH), 5.15 (dd, IH), 4.28 (s, 2H), 25 4.26 (t, 2H), 3.22 (t, 2H), 2.98-2.91 (m, 4H), 2.52 (br s, 4H), 2.31 (s, 3H). Example 26 5-Bromo-2,3-dihydro-6-(l-methylpiperidin-4-yl)-l-[4-(pyridin-4-yl)naphth-l-ylaminocarbonyl]-lH-indole 30 The title compound was prepared from 4-(pyridin-4-yl)naphth-l-ylamine (D2) and 5- bromo-2,3-dihydro-6-(l-methylpiperidin-4-yl)-lH-indole (D39) using a similar procedure to Example 4 (11%). -64- Printed from Mimosa WO 98/50358 PCT/EP98/02262 !h NMR (250 MHz, d6DMSO) 8(ppm). 8.95 (s, IH), 8.78 (dd, 2H), 8.19 (dd, IH), 7.93 (m, IH), 7.85 (dd, IH), 7.54-7.69 (m, 6H), 7.46 (s, IH), 4.37 (t, 2H), 3.27 (t, 2H), 2 95 (br d, 2H), 2.82 (m, IH), 2.27 (s, 3H), 2 10 (m, 2H), 1.65 (m, 4H) 5 Example 27 5-Chloro-2,3-dihydro-6-(4-methylpiperaziii-l-yl)-l-[5-(pyridiii-4-yl)naphth-l-ylaminocarbonyl]-l H-indole The title compound was prepared from 5-(pyridin-4-yl)naphth-l-yl isocyanate (D4) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar 10 procedure to Example 2. 'H NMR (250 MHz, CDC13) S (ppm): 8.73 (d, 2H), 8.02 (d, IH), 7.83 (s, IH), 7.74 (d, IH), 7.70 (d, IH), 7.59 (t, IH), 7.47 - 7.40 (m, 4H), 7.17 (s, IH), 6.86 (s, IH), 4.27 (t, 2H), 3.25 (t, 2H), 3.11 (br s, 4H), 2.66 (br s, 4H), 2.38 (s, 3H) 15 Example 28 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yI)-l-[5-(pyridin-4-yl)naphth-l-ylaminocarboiiyl]-lH-indoIe The title compound was prepared from 5-(pyridin-4-yl)naphth-l-yl isocyanate (D4) and 5-bromo-2,3-dihydro-6-(4-methylpiperazm-l-yl)-lH-indole (D15) using a similar 20 procedure to Example 2. 'H NMR (250 MHz, CDC13) 8 (ppm): 8.73 (d, 2H), 8.02 (d, IH), 7.84 (s, IH), 7.75 (d, IH), 7.72 (d, IH), 7.59 (t, IH), 7.50 - 7.44 (m, 2H), 7.41 (d, 2H), 7.37 (s, IH), 6.78 (s, IH), 4.27 (t, 2H), 3 26 (t, 2H), 2.97 (br s, 4H), 2.56 (br s, 4H), 2.32 (s, 3H). 25 Example 29 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yI)-l-(quinolin-6-ylaminocarbonyI)-1 H-indole The title compound was prepared from quinolm-6-yl isocyanate (D26) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole (intermediate 3 in WO 95/06627) using a 30 similar procedure to Example 2. 'H NMR (250 MHz, CDC13) 8 (ppm): 8.78 (dd, IH), 8 19 (d, IH), 8.13 (dd, IH), 8.03 (d, IH), 7.73 (s, IH), 7.58 (dd, IH), 7.37 (dd, IH), 6.83 (s, IH), 6.74 (s, IH), 4.13 (t, 2H), 3.84 (s, 3H), 3.20 (t, 2H), 3.16 (br s, 4H), 2.66 (br s, 4H), 2.37 (s, 3H). -65 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 Example 30 l-[4-(f-Butoxycarbonylamino)phenylaminocarbonyI]-5-chloro-2,3-dihydro-6-(4-methyIpiperazin-l-yl)-lH-indole 5 The title compound was prepared from 4-(f-butoxycarbonylamino)anihne (D40) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 4 (29%). ]H NMR (250MHz, d6DMSO) 8(ppm). 9.25 (s, IH), 8.45 (s, IH), 7.78 (s, IH), 7.40 (m, 4H), 7.22 (s, IH), 4.12 (t, 2H), 3.11 (t, 2H), 2.89 (m, 4H), 2.50 (m, 4H), 2.25 (s, 3H), 1.48 10 (s, 9H) Example 31 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-(quinolin-6-ylaminocarbonyl)-1 H-indole 15 The title compound was prepared from quinolin-6-yl isocyanate (D26) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D15) using a similar procedure to Example 2. 'H NMR (250 MHz, CDC13) 8 (ppm)- 8.82 (dd, IH), 8.17 (d, IH), 8 13 (dd, IH), 8.05 (d, IH), 7 85 (s, IH), 7.57 (dd, IH), 7.39 (t, IH), 7.36 (s, IH), 6.62 (s, IH), 4 16 (t, 2H), 3.22 20 (t, 2H), 3 12 (t, 4H), 2.63 (br s, 4H), 2.37 (s, 3H). Example 32 6-Bromo-2,3-dihydro-7-(4-methylpiperazin-l-yl)-l-[4-(pyridin-4-yl)naphth-l-ylaminocarbonyl]-l,2,3,4-tetrahydroquinoline 25 The title compound was prepared from 4-(pyridin-4-yl)naphth-l -ylamine (D2) and 6-bromo-7-(4-methylpiperazin-l-yl)-l,2,3,4-tetrahydroquinoline (D33) using a similar procedure to Example 4. 'H NMR (250 MHz, CDClj) 8 (ppm): 8.72 (d, 2H), 8.07 (d, IH), 7.86 (dd, IH), 7.67 (dd, 1H),7.51 (s, IH), 7.47 - 7.40 (m, 6H), 7.26 (s, IH), 3.89 (t, 2H), 3 03 (t, 4H), 2.81 (t, 2H), 30 2.56 (t, 4H), 2.31 (s, 3H), 2.03 (quintet, 2H). Example 33 -66- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-(4-phenoxyphenylaminocarbonyl)-lH-indole The title compound was prepared from 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) and 4-phenoxyphenyl isocyanate using a similar procedure to Example 5 2. 'H NMR (250 MHz, CDC13) 8 (ppm): 7 81 (s, IH), 7.38 - 7.28 (m, 4H), 7.13 (s, IH), 7.10 - 6 96 (m, 5H), 6.43 (s, IH), 4.04 (t, 2H), 3.15 (t, 2H), 3 08 (br s, 4H), 2.58 (br s, 4H), 2.33 (s, 3H). 10 Example 34 5-Chloro-l-[4-(4-chlorophenoxy)phenylaminocarbonyl]-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-l H-indole The title compound was prepared from 5-chloro-2,3-dihydro-6-(4-methylpiperazm-l-yl)-1 H-indole (D13) and 4-(4-chlorophenoxy)aniline using a similar procedure to Example 4 15 'H NMR (250 MHz, CDC13) 8 (ppm): 7.81 (s, IH), 7.38 (d, 2H), 7.26 (d, 2H), 7.14 (s, IH), 6 98 (d, 2H), 6.91 (d, 2H), 6.41 (s, IH), 4.08 (t, 2H), 3.18 (t, 2H), 3.09 (br s, 4H), 2.61 (br s, 4H), 2.35 (s, 3H). Example 35 20 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-(quinolin-6-ylaminocarbonyl)-1 H-indole The title compound was prepared from quinolm-6-yl isocyanate (D26) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 2. 25 'H NMR (250 MHz, CDC13) 5 (ppm): 8.79 (dd, IH), 8.18 (d, IH), 8.13 (dd, IH), 8.03 (d, IH), 7.85 (s, IH), 7.59 (dd, IH), 7.38 (dd, IH), 7.15 (s, IH), 6.90 (s, IH), 4.15 (t, 2H), 3.19 (t, 2H), 3.15 (br s, 4H), 2 67 (br s, 4H), 2.39 (s, 3H). Example 36 30 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l -(3-phenoxyphenylaminocarbonyl)-lH-indole The title compound was prepared from 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) and 3-phenoxyamhne using a similar procedure to Example 4. -67- Pnnted from Mimosa WO 98/50358 PCT/EP98/02262 'H NMR (250 MHz, CDC13) 6 (ppm): 7.77 (s, IH), 7.36 - 6 96 (m, 9H), 6.71 (ddd, IH), 6.46 (s, IH), 4.03 (t, 2H), 3 13 (t, 2H), 3 08 (br s, 4H), 2.60 (br s, 4H), 2.35 (s, 3H) Example 37 5 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyrimidin-2-yI)phenylamino-carbonyl]-lH-indo!e The title compound was prepared from 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-1 H-indole (D13) and 4-(pynmidin-2-yl)phenyl isocyanate (D42) using a similar procedure to Example 2, giving a pale cream powder (69%). 10 'H NMR (250 MHz, CDC13) 5 (ppm): 8.78 (d, 2H), 8 40 (d, 2H), 7.83 (s, IH), 7 60 (d, 2H), 7.15 (m, 2H), 6.56 (s, IH), 4.12 (t, 2H), 3.18 (t, 2H), 3.11 (br s, 4H), 2.60 (br s, 4H), 2.35 (s, 3H). Example 38 15 l-(3-Benzoylphenylaminocarbonyl)-5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 3-aminobenzophenone and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 4. *H NMR (250 MHz, CDC13) 8 (ppm): 7.88 (m, IH), 7.78 - 7 74 (m, 4H), 7.57 (d, IH), 20 7.49 - 7.40 (m, 4H), 7.11 (s, IH), 6.95 (s, IH), 4.10 (t, 2H), 3.16 - 3.04 (m, 6H), 2 63 (br s, 4H), 2 37 (s, 3H). Example 39 l-(4-Benzoylphenylaminocarbonyl)-5-chIoro-2,3-dihydro-6-(4-methylpiperazin-l-25 yl)-l H-indole The title compound was prepared from 4-aminobenzophenone and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l H-indole (D13) using a similar procedure to Example 4 'H NMR (250 MHz, CDC13) 8 (ppm): 7.81 - 7.74 (m, 5H), 7.58 (m, IH), 7.56 (d, 2H), 7.47 (t, 2H), 7.13 (s, IH), 6 85 (s, IH), 4.10 (t, 2H), 3.15 (t, 2H), 3.09 (br s, 4H), 2.59 (br 30 s, 4H), 2.35 (s, 3H). Example 40 -68- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-ChIoro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-(2-methylquinolin-6-ylaminocarbonyl)-l H-indole The title compound was prepared from 6-amino-2-methylquinoline and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) usmg a similar procedure to 5 Example 4. 'H NMR (250 MHz, CDC13) 5 (ppm): 8.05 (d, IH), 7 95 (d, IH), 7.93 (d, IH), 7 83 (s, IH), 7.54 (dd, IH), 7.22 (d, IH), 7.12 (s, IH), 6.75 (s, IH), 4.07 (t, 2H), 3.16 - 3 09 (m, 6H), 2.70 (s, 3H), 2.61 (br s, 4H), 2 35 (s, 3H). 10 Example 41 5-Chloro-2,3-dihydro-l-[4-(fur-2-yl)phenyIaminocarbonyl]-6-(4-methyIpiperazin-l-yl)-l H-indole The title compound was prepared from 5-chloro-2,3-dihydro-l-(4-iodophenylammocarbonyl)-6-(4-methylpiperazin-l-yl)-l H-indole (D43) and 2-15 furylboronic acid in a similar manner to Description 2, obtained as a pale buff powder (64%). 'H NMR (250 MHz, d6DMSO) 8 (ppm): 8.68 (s, IH), 7.82 (s, IH), 7 73 (d, IH), 7.76 (s,4H), 7.25 (s, IH), 6.86 (d, IH), 6.61 (dd, IH), 4.18 (t, 2H), 3.15 (t, 2H), 2 95 (br s, 4H), 2.26 (s, 3H). 2 x CH2 signals obscurred by DMSO signal. 20 Example 42 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(thien-2-yl)phenylaminocarbonyl]-lH-indole The title compound was prepared from 5-chloro-2,3-dihydro-l-(4-25 iodophenylaminocarbonyl)-6-(4-methylpiperazm-l -yl)-l H-indole (D43) and 2- thienylboronic acid m a similar manner to Description 2, obtained as a cream powder (56%). 'H NMR (250 MHz, CDC13) 8 (ppm): 7.82 (s, IH), 7.58 (d, 2H), 7 42 (d, 2H), 7 24 (d, 2H), 7.14 (s, IH), 7.08 (m, IH), 6.45 (s, IH), 4.09 (t, 2H), 3.18 (t, 2H), 3.10 (br s, 4H), 30 2.60 (br s, 4H), 2.35 (s, 3H). Example 43 -69- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yI)-l-[5-(pyridin-4-yl)naphth-l-ylacetyl]-lH-indoline The title compound was prepared from 5-(pyridin-4-yl)naphth-l-ylacetic acid (D25) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar 5 procedure to Example 20. 'H NMR (250 MHz, CDC13) 8 (ppm): 8.73 (dd, 2H), 8.07 (s, IH), 8.01 (d, IH), 7.79 (dd, IH), 7 61 (dd, IH), 7.45 - 7.41 (m, 5H), 7.19 (s, IH), 4.27 (s, 2H), 4.26 (t, 2H), 3 19 (t, 2H), 3 05 (br s, 4H), 2.56 (br s, 4H), 2.32 (s, 3H). 10 Example 44 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yI)-l-[5-(pyridin-4-yl)naphth-l-ylacetyl]-lH-indole The title compound was prepared from 5-(pyndin-4-yl)naphth-l -ylacetic acid (D25) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D15) using a similar 15 procedure to Example 20. 'H NMR (250 MHz, CDC13) 8 (ppm): 8.73 (d, 2H), 8.08 (s, IH), 8.00 (d, IH), 7.78 (dd, IH), 7.60 (dd, IH), 7.44 - 7.41 (m, 5H), 7.37 (s, IH), 4.26 (s, 2H), 4.25 (t, 2H), 3 18 (t, 2H), 3 03 (br s, 4H), 2.56 (br s, 4H), 2.32 (s, 3H) 20 Example 45 5-Chloro-2,3-dihydro-l-[4-(l-methylpiperidin-4-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-l H-indoie The title compound was prepared from 4-(l-methylpiperidin-4-yl)naphth-l-ylamine (D46) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a 25 similar procedure to Example 4. 'h NMR (dihydrochloride salt) (250 MHz, d^MSO) 8 (ppm): 11.06 (br s, IH), 10 94 (br s, IH), 8 82 (s, IH), 8.27 (dd, IH), 8.11 (dd, IH), 7.78 (s, IH), 7.63 (m, 2H), 7.54 (d, IH), 7.42 (d, IH), 7.33 (s, IH), 4.30 (t, partially obscurred, 2H), 3.74 (m, IH), 3.24 (t, 2H), 3.60 - 2.96 (m, 12H), 2.84 (s, 3H), 2.83 (s, 3H), 2.18 (m, 4H) 30 Example 46 5-Chloro-2,3-dihydro-l-[4-(2-metbyIoxazol-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-l -yl)-l H-indole -70- Printed from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 4-(4-aminophenyl)-2-methyloxazole (D47) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 4 as a pale yellow powder (67%). 'H NMR (250 MHz, d^MSO) 5 (ppm): 8.61 (s, IH), 8.30 (s, IH), 7.74 (s, IH), 7.57 (dd, 5 4H), 7.21 (s, IH), 4.13 (t, 2H), 3.08 (m, 6H), 2.75 (s, 3H), 2.38 (s, 3H). 2 x CH2 signals obscurred by H20 signal. Example 47 5-Bromo-2,3-dihy dro-6-(4-methylpiperazin-1 -y 1)-1 - [4-(2-methylpy ridin-4-10 yl)pbenylaminocarbonyl]-lH-indole The title compound was prepared from 4-(2-methylpyridin-4-yl)amhne (D49) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l H-indole (D15) using a similar procedure to Example 4 as a white solid (48%). 'H NMR (250 MHz, CDC13) 8 (ppm): 8.52 (d, IH), 7 83 (s, IH), 7.64 - 7.52 (m, 4H), 15 7.38-7.33 (m, 2H), 7 29 (d, IH), 6.54 (s, IH), 4.11 (t, 2H), 3.19 (t, 2H), 3.09 (br s, 4H), 2.62 (br s, 4H + s, 3H), 2.35 (s, 3H). Example 48 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(2-methylpyridin-4-20 yl)phenylaminocarbonyl]-lH-indole The title compound was prepared from 4-(2-methylpyridin-4-yl)aniline (D49) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 4 as a beige solid (79%). 'H NMR (250MHz, CDC13) 8 (ppm): 8.52(d, IH), 7.82 (s, IH), 7.62-7.50 (m, 25 4H), 7.34 (s, IH), 7.28 (dd, IH), 7.14 (s, IH), 6.52 (s, IH), 4.11 (t, 2H), 3.18 (t, 2H), 3.13-3.04 (m, 4H), 2.61 (s, 3H), 2.60 (br s, 4H), 2.34 (s, 3H). Example 49 5-Chloro-2,3-dihydro-l-[4-(2,6-dimethylpyridin-4-yl)phenylaminocarbonyI]- I 30 6-(4-methylpiperazin-l-yl)-lH-iiidoIe The title compound was prepared from 4-(2,6-dimethylpyndm-4-yl)pheriyl isocyanate (D62) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (Dl 3) using a similar procedure to Example 2 as a white solid (55%). -71 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 ]H NMR (250MHz, CDC13) 8 (ppm): 7.82 (s, IH), 7 60 - 7.50 (m, 4H), 7.16 - 7.11 (m, 3H), 6.63 (s, IH), 4.07 (t, 2H), 3.15 (t, 2H), 3.09 (br s, 4H), 2.61 (br s, 4H), 2.57 (s, 6H), 2.35 (s, 3H). 5 Example 50 5-Bromo-2,3-dihydro-l-[4-(2,6-dimethylpyridin-4-yl)phenylaminocarbonyl]- 6-(4-methyIpiperazin-l -yl)-l H-indole The title compound was prepared from 4-(2,6-dimethylpyridin-4-yl)phenyl isocyanate (D62) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole 10 (D15) using a similar procedure to Example 2 as a white solid (36%) 'H NMR (250MHz, CDC13) 8 (ppm): 7.83 (s, IH), 7.61 - 7.51 (m, 4H), 7 34 (s, IH), 7.16 (s, 2H), 6.54 (s, IH), 4.11 (t, 2H), 3.19 (t, 2H), 3.09 (br s, 4H), 2.62 (br s, 4H), 2 58 (s, 6H), 2.35 (s, 3H). 15 Example 51 2,3-Dihydro-l-[4-(2,6-dimethylpyridin-4-yl)phenylaminocarbonyl]-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 4-(2,6-dimethylpyridin-4-yl)phenyl isocyanate (D62) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazm-l-yl)-lH-20 indole (intermediate 3 m WO 95/06627) using a similar procedure to Example 2 as a beige solid (28%) lH NMR (250MHz, CDC13) 8 (ppm): 7.70 (s, IH), 7.61 - 7.50 (m, 4H), 7.16 (s, 2H), 6 74 (s, IH), 6.51 (s, IH), 4.11 (t, 2H), 3.84 (s, 3H), 3.20 (t, 2H), 3.13 (br s, 4H), 2.62 (br s, 4H), 2.58 (s, 6H), 2.35 (s, 3H). 25 Example 52 5-Chloro-2,3-dihydro-l-[4-(2,6-dimethylpyridin-3-yl)phenylaminocarbonyl]- 6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 4-(2,6-dimethylpyridm-3-yl)phenyl 30 isocyanate (D63) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indoIe (D13) using a similar procedure to Example 2 as a white solid (21%). -72- Printed from Mimosa WO 98/50358 PCT/EP98/02262 'H NMR (250MHz, CDC13) 8 (ppm)- 7.83 (s, IH), 7 48 (d, 2H), 7 40 (d, IH), 7.28 (d, 2H), 7.16 (s, IH), 7 04 (d, IH), 6.49 (s, IH), 4.11 (t, 2H), 3.20 (t, 2H), 3.10 (br s, 4H), 2.60 (br s, 4H), 2.57 (s, 3H), 2.49 (s, 3H), 2.35 (s, 3H). 5 Example 53 5-Bromo-2,3-dihydro-l-[4-(2,6-dimethylpyridin-3-yl)phenylaminocarbonyI]- 6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 4-(2,6-dimethylpyridin-3-yl)phenyl isocyanate (D63) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole 10 (D15) using a similar procedure to Example 2 as a white solid (44%). 'H NMR (250MHz, CDC13) 5 (ppm): 7.84 (s, IH), 7.50 (d, 2H), 7.41 (d, IH), 7.35 (s, IH), 7.29 (d, 2H), 7.06 (d, IH), 6 48 (s, IH), 4.12 (t, 2H), 3.21 (t, 2H), 3.09 (br s, 4H), 2.60 (br s, 4H), 2.57 (s, 3H), 2.49 (s, 3H), 2.35 (s, 3H). 15 Example 54 2,3-dihydro-l-[4-(2,6-dimethylpyridin-3-yl)phenylaminocarbonyI]-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 4-(2,6-dimethylpyridin-3-yl)phenyl isocyanate (D63) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-20 indole (intermediate 3 m WO 95/06627) using a similar procedure to Example 2 as a beige solid (17%). 'H NMR (250MHz, CDC13) 8 (ppm): 7.72 (s, IH), 7.48 (d, 2H), 7.39 (d, IH), 7.25 (d, 2H), 7.03 (d, IH), 6.73 (s, IH), 6.54 (s, IH), 4.09 (t, 2H), 3.83 (s, 3H), 3.18 (t, 2H), 3.12 (br s, 4H), 2.60 (br s, 4H), 2.56 (s, 3H), 2 48 (s, 3H), 2.34 (s, 3H) 25 Example 55 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(5-methyl-l,2,4-oxadiazol-3-yl)phenylaminocarbonyl]-lH-indole The title compound was prepared in an analogous manner to Example 4 from 4-30 (5-methyl-l,2,4-oxadiazol-3-yl)anihne (Ger. Offen DE 2046928) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l H-indole (D13). The product was isolated as a pale cream powder (44%) -73- Printed from Mimosa WO 98/50358 PCT/EP98/02262 'H NMR (250MHz, CDC13) 5 (ppm): 8.04 (d, 2H), 7.81 (s, IH), 7.58(d, 2H), 7.15 (s, IH), 6.53 (s, IH), 4.10 (t, 2H), 3 19 (t, 2H), 3.10 (br s, 4H), 2.65 (s, 3H), 2.60 (br s, 4H), 2.35 (s, 3H). 5 Example 56 5-Chloro-2,3-dihydro-l-[4-(3-methyI-l,2,4-oxadiazol-5-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared in an analogous manner to Example 4 from 4-(3-methyl-l,2,4-oxadiazol-5-yl)amlme(J. Het. Chem. 1980,17 (6), 1273-5) and 10 5-chloro-2,3-dihydro-6-(4-methylpiperazm-l-yl)-lH-indole (D13). The product was isolated as a cream powder (0.13g, 48%). 'H NMR (250MHz, d^MSO) 8 (ppm): 8.81 (s, IH), 7.84 (d, 2H), 7.71 (d, 2H), 7.63 (s, IH), 4.02 (t, 2H), 2.96 (t, 2H), 2.76 (br s, 4H), 2.34 (br s, 4H), 2.07 (s, 3H), 1.93 (s, 3H). NH proton not observed. 15 Example 57 5-Ctaloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[3-(pyrimidin-2-yloxy)phenylaminocarbonyl]-lH-indole The title compound was prepared in analogous manner to Example 4 from 3-20 (pyrimidin-2-yloxy)aniline (D71) and 5-chloro-2,3-dihydro-6-(4-methylpiperazm-1 -yl)-1 H-indole (D13). The product was isolated as a pale buff powder (32%). 'H NMR (250MHz, d6DMSO) 8 (ppm): 8.55 (m, 3H), 7.63 (s, IH), 7.35 (m, 2H), 7.26 - 7.10 (m, 3H), 6.75 (d, IH), 4.02 (t, 2H), 2.99 (t, 2H), 2.78 (br s, 4H), 2.39 (br s, 4H), 2.10 (s, 3H). 25 Example 58 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-{4-[N-methyI-N-(pyrimidin-2-yl)amino]phenylaminocarbonyl}-lH-indole The title compound was prepared in analogous manner to Example 4 from 4-[N-30 methyl-N-(pyrimidin-2-yl)amino]aniline (D73) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13). The product was isolated as a pale cream powder (54%). -74- Printed from Mimosa WO 98/50358 PCT/EP98/02262 'H NMR (250MHz, CDC13) 8 (ppm): 8.34 (d, 2H), 7.80 (s, IH), 7.46 (d, 2H), 7.29 (d, 2H), 7.15 (s, IH), 6.56 (t, IH), 6.42 (s, IH), 4.08 (t, 2H), 3.50 (s, 3H), 3.18 (t, 2H), 3.09 (br s, 4H), 2.60 (br s, 4H), 2.35 (s, 3H). 5 Example 59 5-Bromo-2,3-dihydro-l-[4-(fur-2-yI)phenylaminocarboiiyl]-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared in an analogous manner to Example 4 from 4-(fur-2-yl)aniline (Synthesis 1976,1,40) and 5-bromo-2,3-dihydro-6-(4-10 methylpiperazin-l-yl)-lH-indole (D15). The title compound was isolated as a cream powder (38%). 'H NMR (250MHz, d^MSO) 8 (ppm): 8.60 (s, IH), 7.71 (s, IH), 7.60 (d, IH), 7.54 (s, 4H), 7.32 (s, IH), 6 74 (d, IH), 6.74 (d, IH), 4.08 (t, 2H), 3 2 (br s, 4H), 3.04 (t, 2H), 2.97 (br s, 4H), 2.68 (s, 3H). 15 Example 60 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l -yl)-l - [4-(thien-3~ yl)phenylaminocarbonyl]-lH-indole The title compound was prepared from 5-chloro-2,3-dihydro-l-(4-20 iodophenylaminocarbonyl)-6-(4-methylpiperazin-l-yl)-lH-indole (D43) and 3-thienylboromc acid in a similar manner to Descnption 2, obtained as a cream powder (31%). 'H NMR (250MHz, CDC13) 8 (ppm): 7.83 (s, IH), 7.57 (d, 2H), 7 45 (d, 2H), 7.38 (m, 3H), 7.15 (s, IH), 6.42 (s, IH), 4.10 (t, 2H), 3.18 (t, 2H), 3.10 (br s, 4H), 2.60 25 (br s, 4H), 2.35 (s, 3H). Example 61 5-Bromo-2,3-ditaydro-6-(4-methylpiperazin-l-yl)-l-[4-(thiazol-2-yl)phenylaminocarbonyl]-lH-indole 30 The title compound was prepared from 4-(thiazol-2-yl)anilme (D52) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D15) using a similar procedure to Example 4 (19%). -75- Printed from Mimosa WO 98/50358 PCT/EP98/02262 'H NMR (250MHz, CDC13) 6 (ppm): 7.92 (d, 2H), 7.84 (d, 2H), 7 52 (d, 2H), 7.32 (d, 2H), 6.57 (s, IH), 4.11 (t, 2H), 3.15 (t, 2H), 3.13 (br s, 4H), 2.69 (br s, 4H), 2.42 (s, 3H). 5 Example 62 5-Cbloro-2,3-dihydro-6-(4-methyIpiperazin-l-yl)-l-[4-(thiazoI-2-yl)phenylaminocarbonyl]-lH-indole The title compound was prepared from 5-chloro-2,3-dihydro-l-(4-iodophenylaminocarbonyl)-6-(4-methylpiperazin-l-yl)-lH-indole (D43) and 2-10 bromothiazole using a similar procedure to D51 (8%). 'H NMR (250MHz, CDC13) 8 (ppm): 7.93 (d, 2H), 7.83 (d, 2H), 7.58 (d, 2H), 7.28 (d, IH), 7.14 (s, IH), 6.57 (s, IH), 4.10 (t, 2H), 3.17 (t, 2H), 3 11 (br s, 4H), 2.61 (br s, 4H), 2.35 (s, 3H). 15 Example 63 l-l4-(5-Acetylthien-2-yl)phenylaminocarbonyl]-5-chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-l H-indole The title compound was prepared from 5-chloro-2,3-dihydro-l-(4-iodophenylaminocarbonyl)-6-(4-methylpiperazin-l-yl)-l H-mdole (D43) and 5-20 acetylthien-2-ylboronic acid in a similar manner to Descnption 2, obtained a straw coloured solid (42%). 'H NMR (250MHz, d^MSO) 8 (ppm): 8.77 (s, IH), 7.91 (d, IH), 7.83 (s, IH), 7.70 (m, 3H), 7.55 (d, IH), 7.22 (s, IH), 4.16 (t, 2H), 3.18 (t, 2H), 2.92 (br s, 4H), 2.51 (m, 7H), 2.23 (s, 3H). Urea NH not observed. 25 Example 64 l-(5-Bromonaphth-l-ylacetyl)-5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 5-bromonaphth-l-ylacetic acid (Bull. Soc. 30 Chim. Fr. 1968, 7,2957) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 20 as a light yellow foam (62%). -76- Printed from Mimosa WO 98/50358 PCT/EP98/02262 'H NMR (250MHz, CDC13) 5 (ppm): 8.26 (d, IH), 7.98 (s, IH), 7 95 (d, IH), 7.83 (d, IH), 7.65 (t, IH), 7.45 (d, IH), 7.37 (t, IH), 7.15 (s, IH), 4.22 (s, 2H), 4.19 (t, 2H), 3.15 (t, 2H), 2.95 (br s, 4H), 2 48 (br s, 4H), 2 17 (s, 3H). 5 Example 65 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yI)-l-(8-phenylquinolin-5-ylaminocarbonyl)-lH-indole The title compound was prepared from 5-amino-8-phenylquinohne (D66) and 5-chloro-2,3-dihydro-6-(4-methylpiperazm-l-yl)-lH-indole (D13) using a similar 10 procedure to Example 4, as a cream coloured solid (40%). *H NMR (250MHz, CDC13) 5 (ppm): 8.95 (dd, IH) 8.29 (dd, IH) 7 83 (s, IH), 7 72 - 7.65 (m, 3H), 7.53 - 7.38 (m, 5H), 7.18 (s, IH), 6.67 (s, IH), 4 22 (t, 2H), 3.24 (t, 2H), 3.06 (br s, 4H), 2 56 (br s, 4H), 2.32 (s, 3H) 15 Example 66 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-(8-phenylquinolin-5-ylaminocarbonyl)-lH-indole The title compound was prepared from 5-amino-8-phenylqumoline (D66) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l H-mdole (D15) using a similar 20 procedure to Example 4, as a cream coloured solid (25%) 'H NMR (250MHz, CDC13) 8 (ppm): 8.96 (dd, IH), 8.31 (dd, IH), 7 84 (s, IH), 7.74 - 7.66 (m, 4H), 7.52 - 7 41 (m, 4H), 7.38 (s, IH), 6.65 (s, IH), 4 25 (t, 2H), 3.27 (t, 2H), 3.05 (br s, 4H), 2.57 (br s, 4H), 2.32 (s, 3H). 25 Example 67 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[2-(2-phenylethyl)quinolin-6-ylaminocarbonyI]-l H-indole The title compound was prepared from 6-amino-2-(2-phenylethyl)quinohne (D69) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a 30 similar procedure to Example 4, as a white solid (77%). 'H NMR (250MHz, CDC13) 5 (ppm): 8.09 (d, IH), 8.01 (d, IH), 7 99 (d, IH), 7.85 (s, IH), 7.56 (dd, IH), 7.31 - 7.15 (m, 7H), 6.62 (s, IH), 4.12 (t, 2H), 3.30 -3.11 (m, 10H), 2.61 (br s, 4H), 2.35 (s, 3H). -77- Printed from Mimosa WO 98/50358 PCT/EP98/02262 Example 68 5-Chloro-2,3-dihydro-6-(4-methyIpiperazin-l-yI)-l-[5-(l-methylpiperidin-4-yl)naphth-l-ylaminocarbonyl]-lH-indole 5 The title compound was prepared from 5-(l-methylpiperidin-4-yl)naphth-l-ylamme (D77) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 4as a white solid (15%). *H NMR (250MHz,CDCI3) 5(ppm):7.99 (d, IH), 7 79 (m, 3H), 7.50 (m, 3H), 7.16 (s, IH), 6 70 (s, IH), 4.24 (t, 2H), 3.32 (m, IH), 3.24 (t, 2H), 3 04 (br s, 4H), 2.56 (br s, 6H), 10 2.38 (s, 3H), 2.32 (s, 3H), 2.21 (m, 2H), 1.97 (m, 4H). Example 69 5-Bromo-2,3-dihydro-l-[4-(isoquinolin-4-yI)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole 15 The title compound was prepared from 4-(isoquinolin-4-yl)phenyl isocyanate (D54) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-mdole (D15) using a similar procedure to Example 2, as a white sohd (24%). 'H NMR (250MHz, CDC13) 5 (ppm): 9.25 (s, IH), 8.47 (s, IH), 8.05 (d, IH), 8 01 (d, IH), 7.86 (s, IH), 7.68 (m, 2H), 7.59 (d, 2H), 7.50 (d, 2H), 7.36 (s, IH), 6.57 20 (s, IH), 4 16 (t, 2H), 3.26 (t, 2H), 3.10 (br s, 4H), 2.61 (br s, 4H), 2 36 (s, 3H). Example 70 5-Chloro-2,3-dihydro-l-[4-(isoquinolin-4-yl)phenyIaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole 25 The title compound was prepared from 4-(isoquinolin-4-yl)phenyl isocyanate (D54) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 2, as a white solid (25%). 'H NMR (250MHz, CDC13) 5 (ppm): 9.25 (s, IH), 8.47 (s, IH), 8.02 (d, IH), 7.94 (d, IH), 7 85 (s, IH), 7.67 (m, 2H), 7.61 (d, 2H), 7.49 (d, 2H), 7.16 (s, IH), 6.60 30 (s, IH), 4 16 (t, 2H), 3.25 (t, 2H), 3.18 (br s, 4H), 2.61 (br s, 4H), 2.35 (s, 3H). Example 71 -78- Pnnted from Mimosa WO 98/50358 PCT/EP98/02262 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(quinolin-3-yl)phenylaminocarbonyl]-1 H-indole The title compound was prepared from 4-(quinolin-3-yl)phenyl isocyanate (D56) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-mdole (D15) using a 5 similar procedure to Example 2, as an off white solid (6%). 'H NMR (250MHz, CDC13) 8 (ppm)- 9.17 (d, IH), 8.27 (d, IH), 8 13 (d, IH), 7.85 (m, 2H), 7.62 (m, 6H), 7.34 (s, IH), 6.57 (s, IH), 4.14 (t, 2H), 3.20 (t, 2H), 3.17 (br s, 4H), 2.62 (br s, 4H), 2.37 (s, 3H). 10 Example 72 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(quinolin-3-yl)phenylaminocarbonyl]-lH-indole The title compound was prepared from 4-(quinolin-3-yl)phenyl isocyanate (D56) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a 15 similar procedure to Example 2, as a light beige solid (10%). 'H NMR (250MHz, CDC13) 8 (ppm). 9.17 (s, IH), 8.27 (s, IH), 8.13 (d, IH), 7.87 (d, IH), 7.84 (s, IH), 7.73 (m, 3H), 7.60 (m, 3H), 7.16 (s, IH), 6.54 (s, IH), 4.14 (t, 2H), 3.21 (t, 2H), 3.12 (br s, 4H), 2.62 (br s, 4H), 2.36 (s, 3H). 20 Example 73 5-Chloro-2,3-dihydro-6-(4-methyIpiperazin-l -yl)-l-[(2-methyl-l, 2,3,4-tetrahydroisoquinolin-7-yl)aminocarbonyl]-lH-indole The title compound was prepared from 7-amino-2-methyl-l,2,3,4-tetrahydroisoqumoline (D78) and 5-chloro-2,3-dihydro-6-(4-methylpiperazm-l-25 yl)-lH-indole (D13) usmg a similar procedure to Example 4 as a off-white solid (23%). *H NMR (250MHz,CDC13) 8(ppm): 7.80 (s, IH), 7.10 (m, 4H), 6.36 (s, IH), 4.04 (t, 2H), 3.55 (s, 2H), 3.15 (t, 2H), 3.09 (br s, 4H), 2.87 (m, 2H), 2.66 (m, 2H), 2.59 (br s, 4H), 2.44 (s, 3H), 2,34 (s, 3H). 30 Example 74 5-Bromo-23-dihydro-6-(4-methy lpiperazin-1-yl)-l - [(2-methyl-l ,2,3,4-tetrahydroisoquinoIin-7-yl)aminocarbonyl]-lH-indole -79- Printed from Mimosa WO 98/50358 PCT/EP98/02262 The title compoimd was prepared from 7-amino-2-methyl-l,2,3,4-tetrahydroisoquinoline (D78) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l H-indole (D15) using a similar procedure to Example 4 as an off-white solid (41%) 5 lH NMR (250MHz,CDC13) 5(ppm): 7.80 (s, IH), 7.32 (s, IH), 7.09 (m, 3H), 6.35 (s, IH), 4 05 (t, 2H), 3.55 (s, 2H), 3 16 (t, 2H), 3.07 (br s, 4H), 2.87 (m, 2H), 2.67 (m, 2H), 2 59 (br s, 4H), 2.44 (s, 3H), 2.34 (s, 3H). Example 75 10 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(quHiolin-8-yl)phenylaminocarbonyl]-lH-indole The title compound was prepared from 4-(qumolin-8-yl)phenyl isocyanate (D58) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D15) using a similar procedure to Example 2, as a white solid (52%). 15 'H NMR (250MHz, CDC13) 8 (ppm). 8.94 (m, IH), 8.20 (m, IH), 7.84 (s, IH), 7.82 (d, IH), 7 62 (m, 6H), 7.41 (m, IH), 7.36 (s, IH), 6.53 (s, IH), 4.12 (t, 2H), 3.19 (t, 2H), 3.10 (br s, 4H), 2.61 (br s, 4H), 2.35 (s, 3H) Example 76 20 5-Chloro-6-(4-methylpiperazin-l-yl)-l-[4-(quinolin-8-yl)phenylamraocarbonyI]-lH-indole The title compound was prepared from 4-(quinolin-8-yl)phenyl isocyanate (D58) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 2, as a white solid (71%). 25 'H NMR (250MHz, CDC13) 8 (ppm): 8.93 (m, IH), 8.20 (d, IH), 7.80 (m, 2H), 7.57 (m, 6H), 7.41 (m, IH), 7.15 (s, IH), 6.53 (s, IH), 4.12 (t, 2H), 3 19 (t, 2H), 3.12 (br s, 4H), 2.62 (br s, 4H), 2.37 (s, 3H). Example 77 30 5-Chloro-2,3-dihydro-l-[4-(imidazol-l-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-l H-indole The title compound was prepared in an analogous manner to Example 4 from 4-(imidazol-l-yl)aniline (J. Med. Chem. 1988,31(11), 2136) and 5-chloro-2,3- -80- Printed from Mimosa WO 98/50358 PCT/EP98/02262 dihydro-6-(4-methylpiperazin-1 -yl)-1 H-indole (D13). The product was isolated as a pale cream powder (42%) 'H NMR (250MHz, d6DMSO) 5 (ppm). 8 70 (s, IH), 8.20 (s, IH), 7 81 (s, IH), 7.72 (m, 3H), 7.57 (d, 2H), 7.25 (s, IH), 7.12 (s, IH), 4.21 (t, 2H), 3.15 (t, 2H), 5 2.94 (m, 4H), 2.52 (br s, 4H), 2.25 (s, 3H). Example 78 5-Chloro-2,3-dihydro-6-(4-methyIpiperazin-l-yl)-l-[4-(pyridin-4-yl)phenylaminocarbonyl]-lH-indole 10 The title compound was prepared in an analogous manner to Description 2 from 5-chloro-2,3-dihydro-l-[4-iodophenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-IH-indole (D43) and 4-pyndylboronic acid (J. Med Chem 1997, 40(22), 3542) The product was isolated as a pale yellow solid (46%) 'H NMR (250MHz, d^MSO) 8 (ppm): 8.51 (s, IH), 8.36 (d, 2H), 7.57 - 7 42 (m, 15 7H), 7.00 (s, IH), 3.92 (t, 2H), 2.94 (t, 2H), 2.71 (m, 4H), 2.02 (s, 3H). 4H obscured by DMSO signal Example 79 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l-[(8-phenylquinolin-5-20 yl)aminocarbonyl]-lH-indole The title compound was prepared from 5-amino-8-phenylquinohne (D66) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole (intermediate 3 in WO 95/06627) using a similar procedure to Example 4, as a yellow/brown oil (20%). This was converted to the HCl salt as a yellow solid from acetone. 25 *H NMR (free base) (250MHz, CDCI3) 8 (ppm)- 8.95 (dd, IH), 8.35 (dd, IH), 7.77 -7.65 (m, 4H), 7.52 - 7.37 (m, 5H), 6.79 (s, IH), 6.76 (s, IH), 4.25 (t, 2H), 3.85 (s, 3H), 3.27 (t, 2H), 3 14 (br s, 4H), 2 66 (br s, 4H), 2.37 (s, 3H). Example 80 30 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[(8-phenylquinoIin-4-yl)aminocarbonyl]-l H-indole -81 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 8-phenylquinolin-4-yl isocyanate (D86) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 2, as a yellow solid (75%). *H NMR (250MHz, CDCI3) 8 (ppm): 8.86 (d, IH), 8.15 (d, IH), 7.85 (s, IH), 7.77 -5 7 38 (m, 9H), 7 19 (s, IH), 4 27 (t, 2H), 3.25 (t, 2H), 3.12 (br s, 4H), 2 63 (br s, 4H), 2 37 (s, 3H) Example 81 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[(8-phenyIquinolin-4-10 yl)aminocarbonyl]-lH-indole The title compound was prepared from 8-phenylquinohn-4-yl isocyanate (D86) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D15) using a similar procedure to Example 2, as a yellow solid (75%). *H NMR (250MHz, CDCI3) 8 (ppm): 8 87 (d, IH), 8.16 (d, IH), 7.85 (s, IH), 7.78 -15 7.39 (m, 9H), 7.28 (s, IH), 4.29 (t, 2H), 3.27 (t, 2H), 3.11 (br s, 4H), 2.63 (br s, 4H), 2.37 (s, 3H). Example 82 2,3-Dihydro-5-methoxy-6-(4-methyIpiperazin-l-yl)-l-[(8-phenylquinolin-4-20 yl)aminocarbonyl]-lH-indole The title compound was prepared from 8-phenylquinolin-4-yl isocyanate (D86) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l H-indole (intermediate 3 in WO 95/06627) using a similar procedure to Example 2, as a beige solid (73%) lH NMR (250MHz, CDCI3) 8 (ppm): 8.86 (d, IH), 8.19 (d, IH), 7 79 - 7 38 (m, 9H), 25 7.33 (s, IH), 6.78 (s, IH), 4.28 (t, 2H), 3.86 (s, 3H), 3.27 (t, 2H), 3.14 (br s, 4H), 2.63 (br s, 4H), 2.36 (s, 3H). Example 83 5-Chloro-l-[4-(2,6-dimethylpyridin-4-yl)-3-methylphenylaminocarbonyl]-6-(4-30 methylpiperazin-1 -yl)-l H-indole The title compound was prepared from 4-(2,6-dimethylpyridin-4-yl)-3-methylaniline (D88) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 4 as a pale yellow solid (41%). -82- Printed from Mimosa WO 98/50358 PCT/EP98/02262 'H NMR (250MHz, CDC13) 5 (ppm) 7.82 (s, IH), 7.36 (d, IH), 7.31 (dd, IH), 7 20-7 10 (m, 2H), 6.90 (s, 2H), 6.46 (s, IH), 4.10 (t, 2H), 3.18 (t, 2H), 3.10 (br s, 4H), 2 60 (br s, 4H), 2.56 (s, 6H), 2.35 (s, 3H), 2 27 (s, 3H). 5 Example 84 5-Chloro-2,3-dihydro-l-[3-methyl-4-(6-methylpyridin-2-yI)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 3-methyl-4-(6-methylpyndm-2-yl)aniline (D89) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) 10 using a similar procedure to Example 4 as a pale yellow gum (86%). This was converted to its hydrochloride salt as a pale yellow solid from acetone. 'H NMR (free base) (250MHz, CDC13) 5 (ppm)' 7.83 (s, IH), 7.62 (t, IH), 7.40-7.28 (m, 3H), 7.20-7.14 (m, 2H), 7.09 (d, IH), 6.42 (s, IH), 4.10 (t, 2H), 3.18 (t, 2H), 3.10 (br s, 4H), 2.61 (br s, 7H), 2.36 (s, 3H), 2.35 (s, 3H). 15 Example 85 5-Bromo-2,3-dihydro-l-[3-methyl-4-(6-methylpyridin-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-l H-indole The title compound was prepared from 3-methyl-4-(6-methylpyndin-2-yl)-3-20 methylanihne (D89) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D15) using a similar procedure to Example 4 as a yellow foam (67%). This was converted to its hydrochloride salt as a beige solid from acetone 'H NMR (free base) (250MHz, CDC13) 6 (ppm) 7.83 (s, IH), 7.62 (t, IH), 7 40-7.28 (m, 4H), 7.16 (d, IH), 7.09 (d, IH), 6 42 (s, IH), 4.10 (t, 2H), 3.19 (t, 2H), 3 09 (br s, 4H), 25 2.61 (br s, 7H), 2.36 (s, 3H), 2 35 (s, 3H). Example 86 2,3-Dihydro-5-methoxy-l-[3-methyl-4-(6-methylpyridin-2-yI)phenylaminocarbonyl]- 6-(4-methyIpiperazin-l -yl)-l H-indole 30 The title compound was prepared from 3-methyl-4-(6-methylpyndm-2-yl)aniline (D89) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazm-1 -yl)-1 H-mdole (intermediate 3 in WO 95/06627) using a similar procedure to Example 4 as a pale -83- Printed from Mimosa WO 98/50358 PCT/EP98/02262 yellow foam (84%) This was converted to its hydrochloride salt as a yellow solid from acetone. 'H NMR (free base) (250MHz, CDC13) 8 (ppm): 7.71 (s, IH), 7.61 (t, IH), 7.38-7,28 (m, 3H), 7.16 (d, IH), 7.08 (d, IH), 6.72 (s, IH), 6.42 (s, IH), 4.07 (t, 2H), 3 83 (s, 3H), 3.18 5 (t, 2H), 3.12 (br s, 4H), 2.60 (br s, 7H), 2 36 (s, 3H), 2.34 (s, 3H) Example 87 5-Chloro-2,3-dihydro-l-[5-(6-methylpyridin-2-yl)naphth-l-ylaminocarbonyl)-6-(4-methylpiperazin-1 -yl)-l H-indole 10 The title compound was prepared from 5-(6-methylpyridin-2-yl)naphth-1 -yl isocyanate (D92) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 4 as a pale yellow solid (59%) This was converted to its hydrochloride salt as a pale yellow solid from acetone. 'H NMR (free base) (250MHz, CDC13) 8 (ppm): 7.97 (dd, IH), 7 87(d, IH), 7 85 (s, IH), 15 7 76-7.68 (m, 2H), 7.62-7.55 (m, 2H), 7.50-7.40 (m, IH), 7.33 (d, IH), 7.23 (d, IH), 7.16 (s, IH), 6.80 (s, IH), 4.24 (t, 2H), 3 23 (t, 2H), 3.09 (br s, 4H), 2.67 (s, 3H), 2 61 (br s, 4H), 2.35 (s, 3H). Example 88 20 2,3-Dihydro-5-methoxy-l-[5-(6-methylpyridin-2-yl)naphth-l-yIaminocarbonyl]-6-(4-methy!piperazin-l-yl)-lH-indole The title compound was prepared from 5-(6-methylpyridin-2-yl)naphth-l-yl isocyanate (D92) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole (intermediate 3 in WO 95/06627) using a similar procedure to Example 4 25 as a pale yellow foam (55%). This was converted to its hydrochloride salt as a pale yellow solid from acetone. 'H NMR (free base) (250MHz, CDC13) 8 (ppm): 7.99 (dd, IH), 7.85 (d, IH), 7.82-7.68 (m, 3H), 7.62-7.55 (m, 2H), 7.50-7.41 (m, IH), 7 34 (d, IH), 7.21 (d, IH), 6.76 (s, 2H), 4.24 (t, 2H), 3.85 (s, 3H), 3.26 (t, 2H), 3 15 (br s, 4H), 2.67 (br s, 7H), 2.38 (s, 3H) 30 Example 89 5-Chloro-2,3-dihydro-6-(4-ethylpiperazin-1 -yl)-l -l4-pyridin-4-yl)naphth-l -ylaminocarbonyl]-l H-indole -84- Prmted from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 4-(pyndin-4-yl)naphth-l-ylamine (D2) and 5-chloro-2,3-dihydro-6-(4-ethylpiperazin-l-yl)-lH-indole (D97) using a similar procedure to Example 4, as a beige sohd (60%), The HCl salt was isolated as a yellow solid from acetone 5 *H NMR (free base) (250MHz, CDCI3) 8 (ppm): 8.74 (d, 2H), 8 00 (d, IH), 7 91 (s, IH), 7.91 - 7 86 (m, 2H), 7.61 - 7.42 (m, 5H), 7.19 (s, IH), 6.81 (s, IH), 4 30 (t, 2H), 3 28 (t, 2H), 3.11 (br s, 4H), 2 62 (br s, 4H), 2 48 (q, 2H), 1.11 (t, 3H). Example 90 10 5-Chloro-2,3-dihydro-6-(4-ethyIpiperazin-l-yl)-l-[5-(pyridin-4-yl)naphth-l-ylaminocarbonyI]-lH-indole The title compound was prepared from 5-(pyridin-4-yl)naphth-l-ylamine (D74) and 5-chloro-2,3-dihydro-6-(4-ethylpiperazin-l-yl)-lH-indole (D97) using a similar procedure to Example 4, as a beige solid (68%). The HCl salt was isolated as a yellow solid from 15 acetone ]H NMR (free base) (250MHz, CDCI3) 8 (ppm): 8.74 (d, 2H), 8.02 (d, IH), 7.84 (s, IH), 7.77 (d, IH), 7.71 (d, IH), 7.60 (t, IH), 7.49 (t, IH), 7.45 - 7.41 (m, 3H), 7.19 (s, IH), 6.73 (s, IH), 4.28 (t, 2H), 3.27 (t, 2H), 3.09 (br s, 4H), 2.60 (br s, 4H), 2.46 (q, 2H), 1.09 (t, 3H). 20 Example 91 5-Chloro-2,3-dihy dro-6-(piperazin-l -yl)-l -[4-(pyridin-4-yl)naphth-l -ylaminocarbonyl]-l H-indole hydrochloride A stirred solution of 6-[4-(/er/-butyloxycarbonyl)piperazin-l-yl]-5-chloro-2,3-dihydro-l-25 [4-(pyridin-4-yl)naphth-l-ylaminocarbonyl]-lH-mdole (D100, 345mg, 0.59 mmole) in methanol (30ml) was treated with 1M HCl in ether (3ml). After 18h at room temperature additional HCl in ether (2.5ml) was added. After 24h the mixture was concentrated in vacuo and the residue solidified by trituration with acetone to afford the title compound as a yellow solid (260mg, 84%). 30 *H NMR (250MHz, d6DMSO) 8 (ppm): 9.32 (s, 2H), 9.09 (s, IH), 9.04 (d, 2H), 8.23 -8.19 (m, 3H), 7.88 (dd, IH), 7.77 - 7.59 (m, 5H), 7.30 (s, IH), 4.37 (t, 2H), 3.24 - 3.18 (m, 6H), 3.10 (br s,4H). -85- Printed from Mimosa WO 98/50358 PCT/E P98/02262 Example 92 5-Chloro-2,3-dihydro-6-(piperazin-1 -yl)-l - [5-(pyridin-4-yl)naphth-l -ylaminocarbonyl]-lH-indole hydrochloride The title compound was prepared from 6-[4-(ter*-butyloxycarbonyl)piperazin-l-yl]-5-5 chloro-2,3-dihydro-1 -[5-(pyridin-4-yl)naphth-1 -ylammocarbonyl]- IH-indole (D100) using a similar procedure to Example 91 as a beige solid (60%). !h NMR (250MHz, d^DMSO) 8 (ppm): 9.41 (s, 2H), 9.17 - 9.13 (m, 3H), 8.37 - 8 28 (m, 3H), 7.84 - 7 64 (m, 6H), 7.40 (s, IH), 4 45 (t, 2H), 3.35 - 3.26 (m, 6H), 3.19 (br s, 4H) 10 Example 93 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridazin-3-yl)phenylaminocarbonyl]-lH-indoIe The title compound was prepared from 4-(pyridizin-3-yl)benzoic acid (D102) using a similar procedure to Description 1 to form the isocyanate followed by addition of 5-15 chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 H-indole (D13) to afford the urea as a pale yellow solid (7%). *H NMR (250MHz,CDCI3) 8(ppm): 9.12 (dd, IH), 8.06 (d, 2H), 7.82 (m, 2H), 7.61 (d, 2H), 7.51 (m, IH), 7.14 (s, IH), 6.63 (s, IH), 4.12 (t, 2H), 3.19 (t, 2H), 3.11 (br s, 4H), 2.61 (br s, 4H), 2.36 (s, 3H). 20 Example 94 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridazin-3-yl)phenylaminocarbonyI]-lH-indole The title compound was prepared from 4-(pyndazin-3-yl)benzoic acid (D102) using a 25 similar procedure to Description 1 to form the isocyanate followed by addition of 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l H-indole (D15) to afford the urea as a grey solid (3%). *H NMR (250MHz,CDCI3) 8(ppm): 9.12 (dd, IH), 8.08 (d, 2H), 7.83 (m, 2H), 7.62 (d, 2H), 7.52 (m, IH), 7.34 (s, IH), 6.60 (s, IH), 4.13 (t, 2H), 3.20 (t, 2H), 3.10 (br s, 4H), 30 2.61 (br s, 4H), 2.36 (s, 3H). Example 95 -86- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yI)-l-[4-(pyrazin-2-yI)phenylaminocarbonyl]-lH-indole The title compound was prepared from 4-(pyrazin-2-yl)benzoic acid (D103) using a similar procedure to Description 1 to form the isocyanate followed by addition of 5-5 chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 H-indole (D13) to afford the urea as a pale yellow solid (30%). *H NMR (250MHz,CDCl3) 5(ppm): 9.01 (s, IH), 8.61 (s, IH), 8 47 (d, IH), 8.02 (d, 2H), 7 83 (s, IH), 7 61 (d, 2H), 7.16 (s, IH), 6.55 (s, IH), 4.13 (t, 2H), 3.20 (t, 2H), 3 11 (br s, 4H), 2.61 (br s, 4H), 2.36 (s, 3H) 10 Example 96 5-Bromo-2,3-dihydro-6-(4-methyIpiperazin-l -yl)-l - [4-(py razin-2-yl)phenylaminocarbonyl]-lH-indole The title compound was prepared from 4-(pyrazm-2-yl)benzoic acid (D103) using a 15 similar procedure to Description 1 to form the isocyanate followed by addition of 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D15) to afford the urea as a pale yellow solid (49%). IH NMR (250MHz,CDC13) 8(ppm): 9.00 (s, IH), 8.60 (s, IH), 8.48 (s, IH), 8 01 (d, 2H), 7.83 (s, IH), 7.61 (d, 2H), 7.34 (s, IH), 6.57 (s, IH), 4.13 (t, 2H), 3 20 (t, 2H), 3.10 (br s, 20 4H), 2.62 (br s, 4H), 2.36 (s, 3H). Example 97 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[(2-phenylpyridin-5-yl)aminocarbonyI]-lH-indole 25 The title compound was prepared from 6-phenylnicotinic acid (D104) using a similar procedure to Description 1 to form the isocyanate followed by addition of 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-mdole (D13) to afford the urea as a white solid (48%). lR NMR (250MHz,d6DMSO) 8(ppm): 8 87 (dd, 2H), 8.12 (m, 3H), 7 96 (d, IH), 7 83 (s, 30 IH), 7.47 (m, 3H), 7.28 (s, IH), 4.22 (t, 2H), 3 17 (t, 2H), 2.95 (br s, 4H), 2.54 (br s, obscured by DMSO peak, 4H), 2.26 (s, 3H). Example 98 -87- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[(2-phenylpyridin-5-yl)aminocarbonyl]-lH-indole The title compound was prepared from 6-phenylnicotimc acid (D104) using a similar procedure to Descnption 1 to form the isocyanate followed by addition of 5-bromo-2,3-5 dihydro-6-(4-methylpiperazin-l-yl)-l H-indole (Dl 5) to afford the urea as an off white solid (46%) !h NMR (250MHz,d6DMSO) 5(ppm): 8.86 (dd, 2H), 8.12 (m, 3H), 8 09 (d, IH), 7 83 (s, IH), 7 47 (m, 4H), 4.22 (t, 2H), 3.18 (t, 2H), 2.94 (br s, 4H), 2.53 (br s, obscured by DMSO peak, 4H), 2.26 (s, 3H). 10 Example 99 5-Chloro-2,3-dihydro-l-[4-(6-methylpyridazin-3-yI)phenyIaminocarbonyl]-6-(4-methyIpiperazin-l-yI)-lH-indole The title compound was prepared from 4-(6-methylpyridazm-3-yl)benzoic acid (D105) 15 using a similar procedure to Description 1 to form the isocyanate followed by addition of 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) to afford the urea as a buff solid (23%). *H NMR (250MHz,CDC13) 8(ppm): 8.03 (d, 2H), 7.83 (s, IH), 7.71 (d, IH), 7.58 (d, 2H), 7.35 (d, IH), 7.14 (s, IH), 6.59 (s, IH), 4.11 (t, 2H), 3.18 (t, 2H), 3 11 (br s, 4H), 20 2.74 (s, 3H), 2.60 (br s, 4H), 2.36 (s, 3H). Example 100 5-Bromo-2,3-dihydro-l-[4-(6-methylpyridazin-3-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indoIe 25 The title compound was prepared from 4-(6-methylpyridazin-3-yl)benzoic acid (D105) using a similar procedure to Descnption 1 to form the isocyanate followed by addition of 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D15) to afford the urea as a buff solid (28%). !H NMR (250MHz,CDCI3) 5(ppm): 8.05 (d, 2H), 7.84 (s, IH), 7.72 (d, IH), 7 60 (d, 30 2H), 7.35 (m, 2H), 6.57 (s, IH), 4.13 (t, 2H), 3.20 (t, 2H), 3.10 (br s, 4H), 2.75 (s, 3H), 2.62 (br s, 4H), 2.36 (s, 3H). Example 101 -88- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-3-yl)phenylaminocarbonyl]-lH-indole The title compound was prepared from 5-chloro-2,3-dihydro-l-(4-iodophenylaminocarbonyl)-6-(4-methylpiperazm-l-yl)-lH-indole (D43) and 3-5 pyridylboromc acid (Chem. Pharm. Bull, 1983,31(12), 4573) in a similar manner to Description 2, obtained as a pale cream powder (19%). 'H NMR (250 MHz, d6DMSO) 8 (ppm): 8.81 (s, IH), 8 61 (s, IH), 8.45 (d, IH), 7.96 (d, IH), 7 7 (s, IH), 7.62 (m, 4H), 7.38 (m, IH), 7.14 (s, IH), 4.08 (t, 2H), 3 04 (t, 2H), 2 83 (br s, 4H), 2.15 (s, 3H). 2xCH2 signals obscured by DMSO signal. 10 Example 102 5-Chloro-2,3-dihydro-l-[4-(5-methyIoxazol-2-yI)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-15 IH-indole (D13) and 4-(5-methyloxazol-2-yl)aniline (D107) using a similar procedure to Example 4, obtained as a pale cream powder (63%). 'H NMR (250 MHz, d6DMSO) 8 (ppm): 8.78 (s, IH), 7.72 (m, 5H), 7.20 (s, IH), 6 90 (s, IH), 4.14 (t, 2H), 3 08 (t, 2H), 2.96 (br s, 4H), 2.72 (br s, 4H), 2.38 (s, 3H), 2.33 (s, 3H). 20 Example 103 2,3-Dihydro-5-methoxy-l-[4-(5-methyloxazoI-2-yl)phenylaminocarbonyI]-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l H-indole (Intermediate 3 in WO 95/06627) and 4-(5-methyloxazol-2-yl)anilme 25 (D107) using a similar procedure to Example 4, obtained as a pale cream powder (44%) *H NMR (250 MHz, d6DMSO) 8 (ppm): 8.80 (s, IH), 7.97 (d, 2H), 7.86 (d, 2H), 7.77 (s, IH), 7.08 (s, IH), 7 00 (s, IH), 4.27 (t, 2H), 3.89 (s, 3H), 3.25 (t, 2H), 3.07 (br s, 4H), 2.61 (br s, 4H), 2.52 (s, 3H), 2.37 (s, 3H). 30 Example 104 5-Bromo-2,3-dihydro-l-[4-(5-methyloxazol-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -y 1)-1 H-indole -89- Pnnted from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D15) and 4-(5-methyloxazol-2-yl)aniline (D107) using a similar procedure to Example 4, obtained as a pale cream powder (23%) 'H NMR (250MHz, CDC13) 8 (ppm): 7.94 (d, 2H), 7.82 (s, IH), 7.52 (d, 2H), 7.33 (s, 5 IH), 6.81 (s, IH), 6.58 (d, IH), 4.11 (t, 2H), 3.15 (m, 6H), 2.69 (br s, 4H), 2.42 (s, 3H), 2.39 (s, 3H). Example 105 5-ChIoro-2,3-dihydro-l-[4-(l-methylpyrazol-4-yl)phenylaminocarbonyl]-6-(4-10 methylpiperazin-1 -yl)-lH-indole The title compound was prepared from 4-(l-methylpyrazol-4-yl)benzoic acid (WO 97/43262) using a similar procedure to Description 1 to form the isocyanate followed by addition of 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-mdole (D13) to afford the urea as an off white solid (18%). 15 *H NMR (250MHz,CDC13) 8(ppm). 7.82 (s, IH), 7.72 (s, IH), 7.55 (s, IH), 7.41 (s, 4H), 7.13 (s, IH), 6.44 (s, IH), 4.07 (t, 2H), 3.93 (s, 3H), 3.16 (t, 2H), 3 10 (br s, 4H), 2.60 (br s, 4H), 2.35 (s, 3H). Example 106 20 5-Bromo-2,3-dihydro-l-[4-(l-methylpyrazol-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-l H-indole The title compound was prepared from 4-(l-methylpyrazol-4-yl)benzoic acid (WO 97/43262) using a similar procedure to Description 1 to form the isocyanate followed by addition of 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D15) to afford 25 the urea as a buff solid (30%). lH NMR (250MHz,CDCI3) 8(ppm): 7.83 (s, IH), 7.71 (s, IH), 7.54 (s, IH), 7.40 (s, 4H), 7.31 (s, IH), 6.46 (s, IH), 4.05 (t, 2H), 3.93 (s, 3H), 3.15 (t, 2H), 3 08 (br s, 4H), 2.60 (br s, 4H), 2.35 (s, 3H). 30 Example 107 5-Chloro-l-[4'-cyano-3'-methylbiphenyl-4-aminocarbonyl]-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole -90- Printed from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 4-(4-cyano-3-methylphenyl)benzoic acid (D106) using a similar procedure to Descnption 1 to form the isocyanate followed by addition of 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) to afford the urea as a pale yellow sohd (39%). 5 *H NMR (250MHz,CDCl3) 8(ppm): 7.82 (s, IH), 7.64 (d, IH), 7.44-7.55 (m, 6H), 7.15 (s, IH), 6.52 (s, IH), 4.11 (t, 2H), 3.19 (t, 2H), 3.10 (br s, 4H), 2.60 (br s, 7H), 2 35 (s, 3H) Example 108 10 5-Bromo-l-[4'-cyano-3'-methylbiphenyl-4-aminocarbonyl]-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 H-indole The title compound was prepared from 4-(4-cyano-3-methylphenyl)benzoic acid (D106) using a similar procedure to Descnption 1 to form the isocyanate followed by addition of 5 -bromo-2,3-dihydro-6-(4-methylpiperazm-1 -yl)-1 H-indole (D15) to afford the urea as a 15 buff sohd (28%). *H NMR (250MHz,CDC13) 8(ppm): 7.83 (s, IH), 7.64 (d, IH), 7 42-7.55 (m, 6H), 7.33 (s, IH), 6.54 (s, IH), 4.10 (t, 2H), 3 18 (t, 2H), 3.08 (br s, 4H), 2.60 (br s, 7H), 2 35 (s, 3H). 20 Example 109 5-Chloro-2,3-dihydro-l-[4-(2-methylpyridin-5-yl)phenylaminocarbonyl]-6-(4-methy lpiperazin-1-yl)-1 H-indole The title compound was prepared from 4-(2-methylpyridin-5-yl)benzoic acid (WO 97/43262) using a similar procedure to Descnption 1 to form the isocyanate followed by 25 addition of 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) to afford the urea as a buff sohd (2%). *H NMR (250MHz,CDCI3) 8(ppm): 8.68 (d, IH), 7.82 (s, IH), 7.74 (dd, IH), 7.53 (s, 4H), 7.21 (d, IH), 7 14 (s, IH), 6.50 (s, IH), 4.11 (t, 2H), 3 18 (t, 2H), 3.11 (br s, 4H), 2.59 (br s, 7H), 2.36 (s, 3H). 30 Example 110 5-Bromo-2,3-dihydro-l-[4-(2-methylpyridin-5-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole -91 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 4-(2-methylpyridm-5-yl)benzoic acid (WO 97/43262) using a similar procedure to Descnption 1 to form the isocyanate followed by addition of 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D15) to afford the urea as a buff solid (10%). 5 lH NMR (250MHz,d^DMSO) 5(ppm): 8 79 (d, IH), 8.73 (s, IH), 7.99 (dd, IH), 7 84 (s, IH), 7.71 (q, 4H), 7.43 (s, IH), 7 36 (d, IH), 4.21 (t, 2H), 3.17 (t, 2H), 2.96 (br s, 4H), 2.54 (br s, obscured by DMSO peak, 7H), 2.31 (s, 3H). Example 111 10 5-Chloro-2,3-dihydro-l-[5-(3-methyI-l,2,4-oxadiazol-5-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-l -yl)-l H-indole The title compound was prepared from 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-mdole (D13) and 5-(3-methyl-1,2,4-oxadiazol-5-yl)naphth-1 -ylamine (Dl 11) using a similar procedure to Example 4. The title compound was converted to the hydrochlonde 15 salt as a pale buff powder (59%). 'H NMR (HCl salt) (250MHz, d6DMSO) 5 (ppm): 10 82 (s, IH), 9.03 (s, IH), 8.92 (d, IH), 8.42 (m, 2H), 7.78 - 7.65 (m, 4H), 7.31 (s, IH), 4.34 (t, 2H), 3 48 - 2.94 (m, 10H), 2.80 (d, 3H), 2.54 (s, 3H). 20 Example 112 2,3-Dihydro-5-methoxy-l-[5-(3-methyl-l,2,4-oxadiazol-5-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole (intermediate 3 in WO 95/06627) and 5-(3-methyl-l,2,4-oxadiazol-5-25 yl)naphth-1 -ylamine (D111) in a similar procedure to Example 4. The title compound was converted to the hydrochloride salt as colourless powder (68%). 'H NMR (HCl salt) (250MHz, d6DMSO) 5 (ppm): 10.87 (s, IH), 8,92 (s, IH), 8,87 (d, IH), 8.41 - 8.33 (m, 2H), 7.78 - 7.65 (m, 3H), 7.60 (s, IH), 6.94 (s, IH), 4.30 (t, 2H), 3.77 (s, 3H), 3 40 (m, 4H), 3.20 (m, 4H), 2 89 (t, 2H), 2.75 (d, 3H), 2.53 (s, 3H). 30 Example 113 5-Bromo-2,3-dihydro-l-[5-(3-methyI-l,2,4-oxadiazol-5-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole -92- Printed from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-indole (D15) and 5-(3-methyl-l,2,4-oxadiazol-5-yl)naphth-l-ylamme (Dl 11) in a similar procedure to Example 4. The title compound was converted to the hydrochlonde salt as a pale buff powder (36%) 5 'H NMR (HCl salt) (250MHz, d6DMSO) 5 (ppm): 10.75 (s, IH), 9.07 (s, IH), 8.92 (d, IH), 8.39 (dd, 2H), 7.80 - 7.65 (m, 4H), 7.46 (s, IH), 4.34 (t, 2H), 3.36 - 2.93 (m, 6H), 2 81 (d, 3H), 2.61 (s, 3H). 2xCH2 signals obscurredby H20 signal. Example 114 10 5-Chloro-2,3-dihydro-l-[5-(5-methyloxazol-2-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-1 H-indole (D13) and 5-(5-methyloxazol-2-yl)naphth-l-ylamine (Dl 14) m a similar procedure to Example 4, converted to the hydrochloride salt as a pale yellow power 15 (41%). 'H NMR (HCl salt) (250MHz, d6DMSO) 8 (ppm): 10.94 (s, IH), 9.16 (d, IH), 8.96 (s, IH), 8 18 (dd, 2H), 7.75 (s, IH), 7.70 - 7.59 (m, 3H), 7.30 (s, IH), 7.16 (s, IH), 4 34 (t, 2H), 3.47 (t, 2H), 3 37 - 2 95 (m, 8H), 2.78 (d, 3H) CH3 signal obscurred by DMSO signal 20 Example 115 2,3-Dihydro-5-methoxy-l-[5-(5-methyloxazol-2-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 2,3-dihydro-5-methoxy-6-(4-methylpiperazm-l-25 yl)-lH-indole (intermediate 3 m WO 95/06627) and 5-(5-methyloxazol-2-yl)naphth-l-ylamme (Dl 14) in a similar procedure to Example 4, obtained as the hydrochloride salt as a pale yellow powder (56%). 'H NMR (HCl salt) (250MHz, d6DMSO) 8 (ppm): 10.95 (s, IH), 9.14 (d. IH), 8.79 (s, IH), 8.17 (dd, 2H), 7.69 - 7.58 (m, 4H), 7.17 (s, IH), 6.94 (s, IH), 4.29 (t, 2H), 3.77 (s, 30 3H), 3.38 (m, 4H), 3.16 (m, 4H), 2.95 (t, 2H), 2.77 (d, 3H), 2.51 (s, 3H). Example 116 -93- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Bromo-2,3-dihydro-l-[3-methyl-4-(pyrimidin-2-yI)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 3-methyl-4-(pyrimidin-2-yl)aniline (Dl 15) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D15) using a similar 5 procedure to Example 4 as a beige foam (34%). This foam was converted to its hydrochlonde salt as a yellow solid from acetone 'H NMR (HCl salt) (250MHz, d6DMSO) 6 (ppm): 10.50 (br s, IH), 8.90 (d, 2H), 8 75 (s, IH), 7.84 (m, 2H), 7.60 (m, 2H), 7.43 (m, 2H), 4.20 (t, 2H), 3 54 (d, IH), 3 33 (d, IH), 3 10 (m, 6H), 2 85 (d, 3H), 2.54 (s, 3H) 10 Example 117 2,3-dihydro-5-methoxy-l-[3-methyl-4-(pyrimidin-2-yl)phenylammocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 3-methyl-4-(pyrimidin-2-yl)aniline (D115) and 15 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-mdole (intermediate 3 in WO 95/06627) using a similar procedure to Example 4 as a beige foam (32%). This foam was converted to its hydrochloride salt as a yellow-brown solid from acetone. 'H NMR (HCl salt) (250MHz, d^MSO) 8 (ppm): 10.45 (br s, IH), 8 90 (d, 2H), 8.59 (s, IH), 7.83 (d, IH), 7.67 (s, IH), 7 60 (m, 2H), 7 40 (t, IH), 6.92 (s, IH), 4 15 (t, 2H), 3 77 20 (s, 3H), 3.45 (m, 4H), 3.17 (m, 4H), 2 96 (t, 2H), 2.82 (d, 3H), 2 54 (s, 3H) Example 118 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[3-methyl-4-(pyrimidin-2-yl)phenylaminocarbonyl]-lH-indole 25 The title compound wa prepared from 3-methyl-4-(pyrimidin-2-yl)aniline (Dl 15) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 4 as a beige foam (47%). This foam was converted to its hydrochlonde salt as a yellow solid from acetone. 'H NMR (HCl salt) (250MHz, d6DMSO) 8 (ppm): 10.50 (br s, IH), 8.90 (d, 2H), 8 71 (s, 30 IH), 7.84 (d, IH), 7.82 (s, IH), 7.60 (m, 2H), 7.41 (t, IH), 7.29 (s, IH), 4.20 (t, 2H), 3.53 (d, 2H), 3.37 (d, 2H), 3 14 (m, 6H), 2.86 (d, 3H), 2.54 (s, 3H). Example 119 -94- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Bromo-2,3-dihydro-l-[3-methyl-4-(pyrimidin-5-yI)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-l H-indole The title compound was prepared from 3-methyl-4-(pyrimidin-5-yl)anihne (Dl 16) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l H-indole (D15) using a similar 5 procedure to Example 4 as a foam (82%). This foam was converted to its hydrochlonde salt as an off white solid from acetone. 'H NMR (HCl salt) (250MHz, d6DMSO) 8 (ppm)- 10.65 (br s, IH), 9 18 (s, IH), 8.86 (s, 2H), 8.73 (s, IH), 7.82 (s, IH), 7.62 (s, IH), 7.55 (dd, IH), 7 45 (s, IH), 7.25 (d, IH), 4.19 (t, 2H), 3.54-2.98 (m, 10H), 2.85 (d, 3H), 2.28 (s, 3H). 10 Example 120 5-Chloro-2,3-dihydro-l-[3-methyI-4-(pyrimidin-5-yI)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 3-methyl-4-(pyrimidin-5-yl)anihne (Dl 16) and 5-15 chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 4 as foam (84%). This foam was converted to its hydrochloride salt as an off white sohd from acetone. 'H NMR (HCl salt) (250MHz, d5DMSO) 8 (ppm): 10.67 (br s, IH), 9.18 (s, IH), 8.86 (s, 2H), 8 73 (s, IH), 7.82 (s, IH), 7.58 (s, IH), 7.55 (dd, IH), 7.27 (m, 2H), 4.19 (t, 2H), 20 3.53-3.00 (m, 10H), 2.84 (d, 3H), 2.28 (s, 3H) Example 121 2,3-Dihydro-5-methoxy-l-[3-methyl-4-(pyrimidin-5-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole 25 The title compound was prepared from 3-methyl-4-(pyrimidin-5-yl)aniline (Dl 16) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole (intermediate 3 in WO 95/06627) using a similar procedure to Example 4 as a foam (97%). This foam was converted to its hydrochloride salt as an off white solid from acetone. 'H NMR (HCl salt) (250MHz, d6DMSO) 8 (ppm): 10.74 (br s, IH), 9.18 (s, IH), 8.88 (s, 30 2H), 8.59 (s, IH), 7.60 (m, 3H), 7.22 (d, IH), 6.92 (s, IH), 4.15 (t, 2H), 3 77 (s, 3H), 3 45 (m, 4H), 3.10 (m, 4H), 2.98 (t, 2H), 2.81 (d, 3H), 2.28 (s, 3H). Example 122 -95- Pnnted from Mimosa WO 98/50358 PCT/EP98/02262 5-Bromo-2,3-dihydro-l-[4-(2,6-dimethylpyridin-4-yl)-3-methylphenylaminocarbonyl]-6-(4-methyipiperazin-l-yi)-lH-indole The title compound was prepared from 4-(2,6-dimethylpyridin-4-yl)-3-methylamline (D88) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-5 indole (D15) using a similar procedure to Example 4 as a pale yellow foam (89%) This was converted to its hydrochloride salt as a pale yellow solid from acetone. 'H NMR (free base) (250MHz, CDC13) 8 (ppm). 7 83 (s, IH), 7.38-7.27 (m, 3H), 7.14 (d, IH), 6.90 (s, 2H), 6.47 (s, IH), 4.11 (t, 2H), 3.19 (t, 2H), 3.08 (br m, 4H), 2.60 (br m, 4H), 2.56 (s, 6H), 2.35 (s, 3H), 2.27 (s, 3H). 10 Example 123 2,3-Dihydro-5-methoxy-l-[4-(2,6-dimethylpyridin-4-yl)-3-methylphenylaminocarbonyl]-6-(4-methyipiperazin-l-yl)-lH-indole The title compound was prepared from 4-(2,6-dimethylpyridin-4-yl)-3-15 methylaniline (D88) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-mdole (intermediate 3 in WO 95/06627) using a similar procedure to Example 4 as a pale yellow foam (95%). This was converted to its hydrochloride salt as a yellow solid from acetone. *H NMR (free base) (250MHz, CDC13) 8 (ppm): 7.70 (s, IH), 7.37 (d, IH), 7.30 (dd, IH), 20 7.14 (d, IH), 6.90 (s, 2H), 6.73 (s, IH), 6.42 (s, IH), 4.09 (t, 2H), 3 84 (s, 3H), 3.20 (t, 2H), 3.12 (br, s, 4H), 2.61 (br s, 4H), 2.56 (s, 6H), 2.34 (s, 3H), 2.27 (s, 3H) Example 124 5-Chloro-2,3-dihydro-l-[5-(2,6-dimethylpyridin-4-yl)naphth-l-yIaminocarbonyl]-6-25 (4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 5-(2,6-dimethylpyridin-4-yl)naphth-l-yl isocyanate (D119) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 4 as a white foam (83%). This was converted to its hydrochloride salt as a white solid from acetone 30 !H NMR (free base) (250MHz, CDC13) 8 (ppm): 7.98 (d, IH), 7.83 (s, IH), 7.77-7.69 (m, 2H), 7.60-7.38 (m, 3H), 7.17 (s, IH), 7.07 (s, 2H), 6.75 (s, IH), 4.25 (t, 2H), 3.24 (t, 2H), 3.06 (br m, 4H), 2 62 (s, 6H), 2.56 (br m, 4H), 2.32 (s, 3H). -96- Printed from Mimosa WO 98/50358 PCT/EP98/02262 Example 125 5-Bromo-2,3-dihydro-l-[5-(2,6-dimethylpyridin-4-yl)naphth-l-ylaminocarbonyI]-6-(4-methylpiperazin-l-yl)radoline The title compound was prepared from 5-(2,6-dimethyl-4-pyridyl)-l-naphthyl 5 isocyanate (D119) and 5-bromo-6-(4-methylpiperazin-l-yl)indoline (D15) using a similar procedure to Example 4 as a white foam (64%). This was converted to its hydrochloride salt as a white solid from acetone. 'H NMR (free base) (250MHz, CDCI3) 8 (ppm): 7.98 (d, IH), 7 84 (s, IH), 7.78-7.68 (m, 2H), 7.60-7.38 (m, 3H), 7.36 (s, IH), 7.08 (s, 2H), 6.75 (s, IH), 4.25 (t, 2H), 3.25 (t, 2H), 10 3.05 (br m, 4H), 2.62 (s, 6H), 2.57 (br m, 4H), 2.32 (s, 3H). Example 126 l-[5-(2,6-Dimethyl-4-pyridyI)-l-naphthylaminocarbonyl]-5-metlioxy-6-(4-methylpiperazin-l-yl)-lH-indole 15 The title compound was prepared from 5-(2,6-dimethylpyndin-4-yl)naphth-l-yl isocyanate (D119) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-mdole (intermediate 3 in WO 95/06627) using a similar procedure to Example 4 as a colourless oil (88%). This was converted to its hydrochloride salt as a pale yellow solid from acetone. 20 *H NMR (free base) (250MHz, CDC13) 8 (ppm): 7.99 (d, IH), 7.78 (d, IH), 7.74 (s, IH), 7.68 (d, IH), 7.60-7.36 (m, 3H), 7.08 (s, 2H), 6.76 (s, IH), 6.72 (s, IH), 4.24 (t, 2H), 3.85 (s, 3H), 3.27 (t, 2H), 3.09 (br s, 4H), 2.62 (s, 6H), 2.57 (br m, 4H), 2.32 (s, 3H) Example 127 25 2,3-Dihydro-l-[4-(2,6-dimethylpyridin-3-yl)-3-methylphenylaminocarbonyl]-5- methoxy-6-(4-methylpiperazin-l-yI)-lH-indoIe The title compound was prepared from 4-(2,6-dimethylpyridin-3-yl)-3-methylaniline (D120) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole (intermediate 3 in WO 95/06627) using a similar procedure to Example 4 30 as a pale yellow oil (44%). This was converted to its hydrochloride salt as an orange solid from acetone. -97- Printed from Mimosa WO 98/50358 PCT/EP98/02262 'H NMR (free base) (250MHz, CDC13) 8 (ppm): 7.72 (s, IH), 7.38 (d, IH), 7.32-7 25 (m, 2H), 7 07-7.00 (m, 2H), 6.74 (s, IH), 6.43 (s, IH), 4.09 (t, 2H), 3.84 (s, 3H), 3.20 (t, 2H), 3.15 (br s 4H), 2.65 (br s, 4H), 2.58 (s, 3H), 2.37 (s, 3H), 2.28 (s, 3H), 2.06 (s, 3H). 5 Example 128 5-Bromo-2,3-dihydro-l-[3-methyl-4-(thiazol-2-yl)phenylaminocarbonyI]-6-(4-methylpiperazin-l-yl)-lH-indole The title compound was prepared from 3-methyl-4-(thiazol-2-yl)anilme (D121) and 5-bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D15) using a 10 similar procedure to Example 4 as a foam (64%). This was converted to its hydrochloride salt as a yellow solid from acetone. 'H NMR (HCl salt) (400MHz, d6DMSO) 8 (ppm): 10.74 (br, IH), 8 75 (s, IH), 7.95 (m, IH), 7.83 (s, IH), 7.79 (m, IH), 7.71 (d, IH), 7.61 (s,lH), 7.59 (d, IH), 7.45 (s, IH), 4.20 (t, 2H), 3.45 (d, 2H), 3.35 (d, 2H), 3.25-3.05 (m, 6H), 2.84 (d, 15 3H), 2.56 (s, 3H). Example 129 5-Chloro-2r3-dihydro-l-[3-methyl-4-(thiazol-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-l H-indole 20 The title compound was prepared from 3-methyl-4-(thiazol-2-yl)aniline (D121) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-mdole (D13) using a similar procedure to Example 4 as a beige foam (70%). This was converted to its hydrochloride salt as a yellow solid from acetone. 'H NMR (HCl salt) (400MHz, d6DMSO) 8 (ppm): 10.77 (br, IH), 8.79 (s, IH), 25 7.93 (d, IH), 7.82 (s, IH), 7.79 (d, IH), 7.71 (d, IH), 7.61 (s,lH), 7.59 (d, IH), 7.29 (s, IH), 4.20 (t, 2H), 3.50 (d, 2H), 3.34 (d, 2H), 3.23-3.04 (m, 6H), 2.83 (d, 3H), 2.56 (s, 3H). Example 130 30 2,3-Dihydro-5-methoxy-l-[3-methyl-4-(thiazol-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl>lH-indole The title compound was prepared from 3-methyl-4-(thiazol-2-yl)amhne (D121) and 2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole (intermediate 3 -98- Printed from Mimosa WO 98/50358 PCT/EP98/02262 in WO 95/06627) using a similar procedure to Example 4 as a pale yellow oil (68%). This was converted to its hydrochlonde salt as a yellow solid from acetone. 'H NMR (HCl salt) (400MHz, d6DMSO) 8 (ppm): 10.56 (br, IH), 8.64 (s, IH), 5 7.94 (d, IH), 7.77 (d, IH), 7.69 (d, IH), 7.65 (s,lH), 7.60 (s, IH), 7.58 (d, IH), 6.92 (s, IH), 4 15 (t, 2H), 3.77 (s, 3H), 3.45 (br t, 4H), 3 14 (m, 4H), 2.96 (t, 2H), 2.81 (d, 3H), 2.55 (s, 3H). Example 131 10 l-(5-Acetylnaphth-l-ylaminocarbonyl)-5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l H-indole The title compound was prepared from 5-acetylnaphth-l-ylamine (D124) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 4. This was converted to its hydrochlonde salt as a buff 15 coloured powder (60%). 'H NMR (HCl salt) (250MHz, d^DMSO) 8 (ppm): 10.74 (s, IH), 8.94 (s, IH), 8 46 (d, IH), 8.25 (d, IH), 8 12 (d, IH), 7.74 (s, IH), 7.60 (m, 3H), 7.30 (s, IH), 4.32 (br s, 2H), 3.45-2.90 (m, 10H), 2.75 (d, 6H). 20 Example 132 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yI)-l-[5-(pyrimidin-2-yIoxy)naphth-l-ylaminocarbonylJ-lH-indole The title compound was prepared from 5-(pyrimidin-2-yloxy)naphth-l-ylamine (D125) and 5-chloro-2,3-dihydro-6-(4-methylpiperazm-l-yl)-lH-indole (D13) 25 using a similar procedure to Example 4. This was converted to its hydrochlonde salt as a pale cream powder (61%). 'H NMR (HCl salt) (250MHz, d6DMSO) 8 (ppm): 10.64 (s, IH), 8.93 (s, IH), 8 64 (d, 2H), 7.95 (d, IH), 7.76 (s, IH), 7.69-7.39 (m, 5H), 7.31 (m, 2H), 4.33 (br, 2H), 3.45 (m, 2H), 3.33-3.10 (m, 6H), 2.93 (t, 2H), 2.81 (s, 3H). 30 Example 133 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[5-(pyrimidin-5-yl)naphth-l-ylaminocarbonyl]-lH-indole -99- Printed from Mimosa WO 98/50358 PCT/EP98/02262 The title compound was prepared from 5-(pyrimidin-5-yl)naphth-l-yl isocyanate (D123) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) using a similar procedure to Example 2 as a white foam (43%). This was converted to its hydrochloride salt as a white solid from acetone. 5 'H NMR (HCl salt) (400MHz, d6DMSO) 5 (ppm): 10.48 (br, IH), 9 33 (s, IH), 8 98 (s, IH), 8.95 (d, IH), 8.20 (d, IH), 7.76 (s, IH), 7 57-7.67 (m, 6H), 7.31 (s, IH), 4.39 (t, 2H), 3.43 (2H, obscured by water peak), 3.32 (d, 2H), 3.12-3.24 (m, 4H), 2.94 (t, 2H), 2 80 (d, 3H) 10 Example 134 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l-l5-(pyrimidin-5-yl)naplith-l-ylaminocarbonyl]-lH-indole The title compound was prepared from 5-(pyrimidin-5-yl)naphth-l-yl isocyanate (D123) and2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-lH-indole 15 (intermediate 3 m WO 95/06627) using a similar procedure to Example 2 as a white foam (50%). This was converted to its hydrochloride salt as a white solid from acetone. 'H NMR (HCl salt) (400MHz, d6DMSO) 8 (ppm). 10.38 (br, IH), 9.32 (s, IH), 8.98 (s, 2H), 8.78 (s, IH), 8.18 (d, IH), 7.64 (t, IH), 7.58 (m, 5H), 6.94 (s, IH), 4.30 (t, 2H), 3.77 20 (s, 3H), 3.42 (4H, obscured by water peak), 3.12-3.23 (m, 4H), 2.89 (t, 2H), 2.78 (d, 3H). Example 135 5-Chloro-l-(5-cyanonaphth-l-ylaminocarbonyl)-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole 25 The title compound was prepared from 5-cyanonaphth-l-ylamine (D126) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l H-indole (D13) using a similar procedure to Example 4. This was converted to its hydrochloride salt as a cream powder (81%). "H NMR (free base) (250MHz, CDC13) 8 (ppm): 8.17 (d, IH), 8.11 (d, IH), 7.91 (d, IH), 30 7 80 (m, 2H), 7.70 (t, IH), 7.56 (t, IH), 7.18 (s, IH), 6.71 (s, IH), 4.25 (t, 2H), 3.26 (t, 2H), 3.07 (br s, 4H), 2.59 (br s, 4H), 2.34 (s, 3H). Example 136 - 100- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Chloro-2,3-dihydro-l - [5-(5-methyl-l ,2,4-oxadiazol-3-yl)naph th-1-ylaminocarbonyI]-6-(4-methyIpiperazin-l -yl)-l H-indole The title compound was prepared from 5-(5-methyl-l,2,4-oxadiazol-3-yl)naphth-l-ylamine (D130) and 5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole (D13) 5 using a similar procedure to Example 4. This was converted to its hydrochloride salt as a buff coloured powder (84%). 'H NMR (HCl salt) (250MHz, d6DMSO) 8 (ppm): 10.67 (s, IH), 8.98 (s, IH), 8.65 (d, IH), 8.28 (d, IH), 8.19 (d, IH), 7.75-7.61 (m, 4H), 7.31 (s, IH), 4.31 (t, 2H), 3.33-3 13 (m, 6H), 2.97 (t, 2H), 2.80 (s, 3H), 2.75 (s, 3H). 2H signal obscurred by H20 signal 10 Pharmacological Data 5-HTja. 5-HTib and 5-HTid Receptor Binding 15 HEK 293 cells expressing 5-HTia receptors (4 x 107/ml) were homogenised in Tns buffer and stored in 1ml ahquots. CHO cells expressing 5-HT jg receptors (4x10^ cells/ml) were homogenised in Tris buffer and stored in 1.5 ml aliquots CHO cells expressing 5-HTiq receptors (0.563 x 10^/ml) were homogenised in Tris buffer and 20 stored in 1 ml aliquots. 0.4 ml of a cell suspension was incubated with [^H]-5-HT (4nM) for 5-HTib/1D receptors and [3H]-8-OH DP AT (InM) for 5-HT^ receptors in Tns Mg HCl buffer (pH 7.7) and test drug, at 37°C for 45 minutes. Each test drug was tested at 10 concentrations (0.01 mM to 0.3 nM final concentration), with non-specific binding defined using 0.01 25 mM 5-HT. The total assay volume was 0.5 ml. Incubation was stopped by rapid filtration using a Packard Filtermate (filters pre-soaked in 0.3% polyethylemmine) and radioactivity measured by Topcount scintillation counting. pKi values were calculated from the IC50 generated by an iterative least squares curve fitting programme. 30 Examples 5, 9,10, 15,21,24,25,27,28,43,44,45,47,48,49, 50, 52, 53,67,68,69, 70, 71, 72, 76, 78, 80, 81, 82, 83, 89,97, 98 and 110 had pKi values >8.0 at 5-HTi a, 5-HT and 5-HT receptors - 101 - Printed from Mimosa </div>

Claims

<div class="application article clearfix printTableText" id="claims"> CLAIMS

1. A compound of formula (I) or a salt thereof: 5 in which Ra is a group of formula (i) 10 m which pl is phenyl, bicyclic aryl, a 5 to 7 membered heterocychc ring contaimng 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur, or a bicychc heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur; R.1 is hydrogen, halogen, C^.galkyl, C3_6cycloaIkyl, COCi.galkyl, C^alkoxy, hydroxy, hydroxyC \ .galkyl, hydroxyC \ .galkoxy, C \ .galkoxyC\ _5alkoxy, nitro, 15 trifluoromethyl, cyano, SR9, SOR9, S02R9, SO2NR10R11, CO2R10, CONR^R11, CO2NR10RH, CONR* 0(CH2)cCO2R 11, (CH2)cNR10R115 (CH2)cCONR10RH, (CH^NRIOcOR1 1, (CH2)cC02C1_6alkyl, C02(CH2)c0R10, NRlORl 1, NRlOcO^11, NR10CONRl0Rl 1, CR^NOR1 *, NR^COOR11 CNR^NOR11, where R9, R10 and Ru are independently hydrogen or alkyl and c is 1 to 4; 20 R2 is hydrogen, halogen, Ci.galkyi, C3_6cycloalkyl, C3_6cycl°alkenyl, Cj.galkoxy, Cj.galkanoyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, C02R^, CONR^R^, NR^rI 1 where R^O and R* 1 are independently hydrogen or C,_6 alkyl; a is 1, 2 or 3; 25 or Ra is a group of formula (ii) - 102 - intellectual property office of n z 2 0 JUN 2001 received wherein P2 and P3 are independently phenyl, bicyclic aryl, a 5- to 7- membered heterocyclic nng containing 1 to 3 heteroatoms selected from oxygen, nitrogen and 5 sulphur, or a bicyclic heterocyclic group containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur; A is a bond or oxygen, S (0)m where m is 0 to 2, carbonyl, CH2, -CH2CH2-, or NR^ where is hydrogen or Ci_6alkyl; R1 is as defined above for formula (i) or R1 is a 5 to 7-membered heterocyclic ring, 10 containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur, optionally substituted by C[.6 alkyl, halogen or C,_6 alkanoyl; R2 and R^ are independently hydrogen, halogen, C^alkyl, C3_6cycloalkyl, C3_6cycloalkenyl, Cj.galkoxy, Cj.galkanoyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CC^R^, CONR^^R^, NRI^rI 1 where R^ and R* * are 15 independently hydrogen or C,^ alkyl; and a and b are independently 1, 2 or 3; Y is -NH-, -NR^- where is Cj.galkyl, or Y is -CH2- or -O-; V is oxygen or sulphur; 20 D is nitrogen, carbon or a CH group, W is (CR^R^)t where t is 2, 3 or 4 and R^ and Rl7 are independently hydrogen or C^.^alkyl or W is (CR16r17)u_j where u is 0, 1, 2 or 3 and J is oxygen, sulphur, CR^=CR^, CR^=N, =CR^O, =CR^s or =CR16-Nr17-X is nitrogen or carbon; Rb is hydrogen, halogen, hydroxy, .galley 1, trifluoromethyl, Cj.galkoxy, C2_6alkenyl, 25 C3_7cycloalkyl optionally substituted by C^alkyl, or aryl; Rc is hydrogen or Cj.galkyl; and — is a single bond when X is nitrogen or a single or double bond when X is carbon. 2 A compound according to claim 1 in which R^ is a halogen atom. 30 - 103 - intellectual property office of nz.

2 0 JUN 2001 received WO 98/50358 PCT/EP98/02262

3. A compound according to claim 1 or 2 in which R2 and/or R^ are each hydrogen, halogen or a Cj.g alkyl group.

4. A compound accordmg to any of the preceding claims in which P1 and P2 are 5 phenyl, naphthyl or quinolinyl.

5. A compound according to any of the preceding claims in which Y is -NH-

6. A compound according to any of the preceding claims in which D is nitrogen 10 and W is a group of formula -(CH2)2- •

7. A compound according to any of the preceding claims in which R^ is a Cj_ galkoxy group. 15

8. A compound according to any of the preceding claims in which X is nitrogen

9. A compound according to claim 1 which is: 1 -[(4-bromo-3-methylphenyl)aminocarbonyl]-5-methoxy-6-(4-methylpiperazin-1 -yl)-1H-mdole, 20 l-[(4-bromo-3-methylphenyl)aminocarbonyl]-2,3-dihydro-5-methoxy-6-(4-methylpiperazin-1 -yl)-1 H-indole, l-[(2,3-dichlorophenyl)aminocarbonyl]-2,3-dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l H-indole, 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-1 -yl)-1 -[4-(pyndin-4-yl)naphth-1 -25 ylammocarbonyl]-1 H-indole, 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l-[5-(pyndin-4-yl)naphth-l-ylammocarbonyl]-1 H-indole, l-[2,3-Dichloro-4-(pyndin-4-yl)phenylaminocarbonyl]-2,3-dihydro-5-methoxy-6-(4-methylpiperazin-1 -yl)-1 H-indole, 30 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l-(quinolin-5-ylaminocarbonyl)-lH-indole, 2,3 -Dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(pyridin-4-yl)naphth-1 -ylaminocarbonyl]-lH-indole, -104- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l -yl)-1 -[4-(pyndm-4-yl)naphth-1 -ylammocarbonyl]-1 H-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-1 -[4-(pyridin-4-yl)naphth-1 -ylammocarbonyl]-1 H-indole 5 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyndin-4-yl)phenylaminocarbonyl]-lH-indole, 5-Bromo-l-[3-chloro-4-(pyndin-4-yl)phenylaminocarbonyl]-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 H-mdole, 2,3-Dihydro-5-methyl-6-(4-methylpiperazm-l-yl)-l-[4-(pyridin-4-yl)naphth-l-10 ylaminocarbonyl]-lH-indole, l-[3-Chloro-4-(pyridin-4-yl)phenylammocarbonyl]-2,3-dihydro-5-methyl-6-(4-methy lpiperazm-1 -yl)-1 H-mdole, 2,3-Dihydro-6-(4-methylpiperazin-l -yl)-1 -[4-(pyridin-4-yl)naphth-1 -ylaminocarbonyl]-5-vinyl-1 H-indole, 15 2,3-Dihydro-5-ethyl-6-(4-methylpiperazin-l-yl)-l-[4-(pyndin-4-yl)naphth-l-ylammocarbonyl]-1 H-indole, l-[3-Chloro-4-(pyridin-4-yl)phenylaminocarbonyl]-2,3-dihydro-5-ethyl-6-(4-methylpip erazin-1 -yl)-1 H-indole, 2,3-Dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyndin-4-yl)naphth-l-ylaminocarbonyl]-5-20 trifluoromethyl-IH-indole, l-[3-Chloro-4-(pyridin-4-yl)phenylaminocarbonyl]-2,3-dihydro-6-(4-methylpiperazin-l-yl)-5-trifluoromethyl-1 H-indole, 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-1 -yl)-1 -[4-(pyndin-4-yl)naphth-l -ylacetyl] -1 H-indole, 25 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-1 -yl)-l -[5-(pyridin-4-yl)-naphth-1 -ylacetyl]-lH-indole, 2,3-Dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(pyridin-4-yl)naphth-1 -ylacetyl]-1 H-indole 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l -yl)-l -[4-(pyridm-4-yl)naphth-1 -ylacetyl]-1 H-mdole, 30 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridm-4-yl)naphth-l-ylacetyl]-IH-indole, 2,3-Dihydro-6-(4-methylpiperazin-1 -yl)-l -[4-(pyndm-4-yl)naphth-1 -ylacetyl]-5-vinyl-lH-indole, -105- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Bromo-2,3-dihydro-6-( 1 -methylpiperidin-4-yl)-1 -[4-(pyndin-4-yl)naphth-1 -ylammocarbonyl]- 1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[5-(pyridin-4-yl)naphth-1 -ylammocarbonyl]-1 H-indole, 5 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l -yl)- l-[5-(pyridin-4-yl)naphth-1 -ylammocarbonyl]-1 H-indole, 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l-(quinolin-6-ylaminocarbonyl)-lH-mdole, 2,3-Dihydro-l-[4-(/-butoxycarbonylamino)phenylaminocarbonyl]-5-chloro-6-(4-10 methylpiperazin-l-yl)-l H-indole, 5-Bromo-2,3 -dihydro-6-(4-methylpiperazin-1 -yl)-1 -(qumolm-6-ylammocarbonyl)-1H-indole, 6-Bromo-7-(4-methylpiperazm-1 -yl)-1 -[4-(pyridm-4-yl)naphth-1 -ylaminocarbonyl]-1,2,3,4-tetrahydroquinolme, 15 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -(4-phenoxyphenylaminocarbonyl)-1 H-indole 5-Chloro-2,3-dihydro-l-[4-(4-chlorophenoxy)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-l H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -(quinolin-6-ylaminocarbonyl)-1H-20 indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-(3-phenoxyphenylaminocarbonyl)-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pynmidin-2-yl)phenylammo-carbonyl]-1 H-indole, 25 l-(3-Benzoylphenylaminocarbonyl)-5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-lH-indole, 1 -(4-Benzoylphenylaminocarbonyl)-5-chloro-2,3 -dihydro-6-(4-methylpiperazin-1 -yl)-l H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-(2-methylquinohn-6-30 ylammocarbonyl)-1 H-indole, 5-Chloro-2,3-dihydro-l-[4-(fur-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-1 H-indole, -106- Pnnted from Mimosa WO 98/50358 PCT/EP98/02262 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(thien-2-yl)phenylammocarbonyl]-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[5-(pyridin-2-yl)naphth-l-ylacetyl]-1 H-indole, 5 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[5-(pyridin-4-yl)naphth-l-ylacetyl]- lH-indole, 5-Chloro-2,3-dihydro-1 -[4-( 1 -methylpiperidin-4-yl)naphth-1 -ylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)- IH-indole, 5-Chloro-2,3-dihydro-l-[4-(2-methyloxazol-4-yl)phenylaminocarbonyl]-6-(4-10 methylpiperazm-1 -yl)-1 H-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(2-methylpyridin-4-yl)phenylamino-carbonyl]-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(2-methylpyndin-4-yl)phenylaminocarbonyl]-lH-indole, 15 5-Chloro-2,3-dihydro-1 -[4-(2,6-dimethylpyndin-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)- IH-indole, 5-Bromo-2,3-dihydro-l-[4-(2,6-dimethylpyridin-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 2,3-Dihydro-l-[4-(2,6-dimethylpyridin-4-yl)phenylaminocarbonyl]-5-methoxy-6-20 (4-methy lpiperazin-1 -yl)-1 H-mdole, 5-Chloro-2,3-dihydro-l-[4-(2,6-dimethylpyndm-3-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Bromo-2,3-dihydro-l-[4-(2,6-dimethylpyndin-3-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 25 2,3-Dihydro-1 -[4-(2,6-Dimethylpyridin-3-yl)phenylaminocarbonyl]-5-methoxy-6-(4-methylpiperazin-1 -yl)-1 H-mdole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(5-methyl-l,2,4-oxadiazol-3-yl)phenylaminocarbonyl]-1 H-indole, 5-Chloro-2,3-dihydro-l-[4-(3-methyl-l,2,4-oxadiazol-5-30 yl)phenylaminocarbonyl]-6-(4-methylpiperazin-l -yl)- IH-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[3-(pyrimidin-2-yloxy)phenylaminocarbonyl]-1 H-indole, -107 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-{4-[N-methyl-N-(pyrimidin- 2-yl)amino]phenylaminocarbonyl}-lH-mdole, 5-Bromo-2,3-dihydro-l-[4-(fur-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-indole, 5 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(thien-3-yl)phenylaminocarbony 1]-1 H-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(thiazol-2-yl)phenylamino-carbonyl]-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l -yl)-1 -[4-(thiazol-2-yl)phenylaimno-10 carbonyl]-IH-indole, l-[4-(5-Acetylthien-2-yl)phenylaminocarbonyl]-5-chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 H-indole, l-(5-Bromonaphth-l-ylacetyl)-5-chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-1 H-indole, 15 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l -yl)-1 -(8-phenylquinohn-5-y laminocarbonyl)-1 H-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-l -(8-phenylquinolin-5-ylaminocarbonyl)-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[2-(2-phenylethyl)quinolin-6-20 ylaminocarbonyl]-lH-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[5-(l-methylpiperidin-4-yl)naphth-l-ylaminocarbonyl]-1 H-indole, 5-Bromo-2,3-dihydro-l-[4-(isoquinolin-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 25 5-Chloro-2,3-dihydro-l-[4-(isoquinolin-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(quinolm-3-yl)pheny laminocarbonyl]-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(quinolin-3-30 yl)phenylaminocarbonyl)]-lH-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)aminocarbonyl]-lH-indole, -108 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)aimnocarbonyl]-lH-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(quinolin-8-yl)phenylaminocarbonyl]-1 H-indole, 5 5-Chloro-2,3-dihydro-6-(4-methylpiperazm-1 -yl)-1 -[4-(quinolin-8-yl)phenylaminocarbonyl]-1 H-indole, 5-Chloro-2,3-Dihydro-1 -[4-(imidazol-1 -yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(pyridm-4-10 yl)phenylaminocarbonyl]-lH-indole, 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-l-yl)-l-[(8-phenylqumolm-5-yl)ammocarbonyl]-1 H-indole 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[(8-phenylquinolin-4-yl)aminocarbonyl]-1 H-indole, 15 5-Bromo-2,3-dihydro-6-(4-methylpiperazm-l-yl)-l-[(8-phenylquinolm-4-yl)aminocarbonyl]-1 H-indole, 2,3-Dihydro-5-methoxy-6-(4-methylpiperazin-1 -yl)-1 -[(8-phenylquinohn-4-yl)aminocarbonyl]-1 H-indole, 5-Chloro-2,3-dihydro-l-[4-(2,6-dimethyl-pyridin-4-yl)-3-methylphenylaminocarbonyl]-6-20 (4-methylpiperazin-1 -yl)-1 H-indole, 5-Chloro-2,3-dihydro-l-[3-methyl-4-(6-methylpyridin-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Bromo-2,3-dihydro-l-[3-methyl-4-(6-methylpyridin-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 25 2,3-Dihydro-5-methoxy-l-[3-methyl-4-(6-methylpyridin-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Chloro-2,3-dihydro-l-[5-(6-methylpyndin-2-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-mdole, 2,3-Dihydro-5-methoxy-1 -[5-(6-methylpyridin-2-yl)naphth-1 -ylammocarbonyl]-6-(4-30 methylpiperazin-1 -yl)-1 H-indole, 5-Chloro-2,3-dihydro-6-(4-ethylpiperazin-l-yl)-l-[4-(pyndin-4-yl)naphth-l-ylammocarbony 1]-1 H-indole, -109- Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Chloro-2,3-dihydro-6-(4-ethylpiperazin-1 -yl)-1 -[5-(pyndm-4-yl)naphth-1 -ylammocarbonyl] -1 H-indole, 5-Chloro-2,3-dihydro-6-(piperazin-l-yl)-l-[4-(pyridm-4-yl)naphth-l-ylaminocarbonyl]-lH-mdole hydrochloride, 5 5-Chloro-2,3-dihydro-6-(piperazin-1 -yl)-1 -[5-(pyridin-4-yl)naphth-1 -ylammocarbonyl]-lH-indole hydrochloride, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridazin-3-yl)phenylaminocarbonyl]-1 H-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyndazin-3-10 yl)phenylaminocarbonyl]-l H-indole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-1 -yl)-1 -[4-(pyrazin-2-yl)phenylaminocarbonyl]-1 H-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazm-l-yl)-l-[4-(pyrazin-2-yl)phenylaminocarbonyl]-lH-indole, 15 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l -yl)- l-[(2-phenylpyndin-5-yl)aminocarbonyl]-1 H-indole, 5-Bromo-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[(2-phenylpyndin-5-yl)aminocarbonyl] -1 H-indole, 5-Chloro-2,3-dihydro-l-[4-(6-methylpyridazin-3-yl)phenylaminocarbonyl]-6-(4-20 methylpiperazin-1 -yl)-IH-indole, 5-Bromo-2,3-dihydro-l-[4-(6-methylpyridazin-3-yl)phenylaminocarbonyl]-6-(4-methy lpiperazm-1 -yl)-1 H-mdole, 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[4-(pyridin-3-yl)phenylaminocarbonyl]-lH-indole, 25 5-Chloro-2,3-dihydro-l-[4-(5-methyloxazol-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-mdole, 2,3-Dihydro-5-methoxy-l-[4-(5-methyloxazol-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-mdole, 5-Bromo-2,3-dihydro-l-[4-(5-methyloxazol-2-yl)phenylaminocarbonyl]-6-(4-30 methylpiperazin-1 -y 1)-1 H-indole, 5-Chloro-2,3-dihydro-1 -[4-( 1 -methylpyrazol-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, -110 - Printed from Mimosa WO 98/50358 PCT/EP98/02262 5-Bromo-2,3-l-[4-(l-methylpyrazol-4-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-l-yl)-lH-mdole, 5-Chloro-2,3-dihydro-l-[4'-cyano-3'-methylbiphenyl-4-aminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5 5-Bromo-2,3-dihydro-l-[4'-cyano-3'-methylbiphenyl-4-aminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Chloro-2,3-dihydro-l-[4-(2-methylpyndin-5-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Bromo-2,3-dihydro-l-[4-(2-methylpyridin-5-yl)phenylaminocarbonyl]-6-(4-10 methylpiperazin-1 -yl)-1 H-indole, 5-Chloro-2,3-dihydro-l-[5-(3-methyl-l,2,4-oxadiazol-5-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 2,3-Dihydro-5-methoxy-l-[5-(3-methyl-l,2,4-oxadiazol-5-yl)naphth-l-ylaminocarbonyl]- 6-(4-methylpiperazin-1 -yl)-1 H-indole. 15 5-Bromo-2,3-dihdyro-l-[5-(3-methyl-l,2,4-oxadiazol-5-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-l H-indole, 5-Chloro-2,3-dihydro-l-[5-(5-methyloxazol-2-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 2,3-Dihydro-5-methoxy-l-[5-(5-methyloxazol-2-yl)naphth-l-ylaminocarbonyl]-6-(4-20 methylpiperazin-1 -yl)-1 H-indole, 5-Bromo-2,3-dihydro-l-[3-methyl-4-(pyrimidin-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 2,3-Dihydro-5-methoxy-l-[3-methyl-4-(pyrimidin-2-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 25 5-Chloro-2,3-dihydro-6-(4-methylpiperazin-l-yl)-l-[3-methyl-4-(pynmidin-2-yl)phenylaminocarbonyl]-1 H-indole, 5-Bromo-2,3-dihydro-l-[3-methyl-4-(pyiunidm-5-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-l H-indole, 5-Chloro-2,3-dihydro-l-[3-methyl-4-(pyrimidin-5-yl)phenylammocarbonyl]-6-(4-30 methylpiperazin-1 -yl)-lH-indole, 2,3-Dihydro-5-methoxy-l-[3-methyl-4-(pyrimidin-5-yl)phenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, - Ill - Printed from Mimosa 5-Bromo-2,3-ciihydro-1 -[4-(2,6-dimethylpyridin-4-yl)-3-methylphenylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 2,3-Dihydro-5-methoxy-l-[4-(2,6-dimethylpyridin-4-yl)-3-methylphenylaminocarbonyl]- 6-(4-methylpiperazm-1 -yl)-1 H-indole, 5 5-Chloro-2,3-dihydro-l-[5-(2,6-dimethylpyndin-4-yl)naphth-l-ylaminocarbonyl]-6-(4-methylpiperazin-1 -yl)-1 H-indole, 5-Bromo-2,3-dihydro-l-[5-(2,6-dimethylpyndin-4-yl)naphth-l-ylammocarbonyl]-6-(4-methy lpiperazin-1 -yl)-1 H-indole, 2,3-Dihydro-l-[5-(2,6-dimethylpyndin-4-yl)naphth-l-ylammocarbonyl]-5-methoxy-6-(4-10 methylpiperazin-1 -yl)-1 H-indole or a pharmaceutically acceptable salt thereof.

10 A process for the preparation of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof which comprises: 15 (a) where D is nitrogen and Y is NH , coupling a compound of foimula (II)- Ra -NC(=V) (II) in which Ra and V are as defined in claim 1 or a protected derivative thereof with a compound of formula (III). 20 in which W, X, R^ and Rc are as defined in claim 1, or a protected derivative thereof; or (b) where D is nitrogen and Y is NH or NR^ , reacting a compound of formula (IV) 25 Ra -NH2 or Ra-NR5H (IV) in which Ra and R5 are as defined in claim 1 with a compound of formula (III) together with an appropnate urea forming agent; (c) where D is nitrogen, reacting a compound of formula (V) intellectual property office of nz. - 112 - 2 0 JUN 2001 received ' f if Ra _y- (0=0) - l2 (v) m which Ra is as defined in claim 1, Y is -CH2* or -O- and L- is an appropnate leaving group, with a compound of formula (HI): (d) where D is carbon or CH, reacting a compound of formula (VI) Ra -NH2 (VI) m which Ra is as defined m claim 1 with a compound of formula (VII) (VII) m which D is carbon or CH, W, X, R^ and Rc are as defined in claim 1 and L2 is an appropnate leaving group and optionally thereafter: • removing any protecting groups, • converting a compound of formula (I) into another compound of formula (I), • forming a pharmaceutically acceptable salt.

11. A compound according to any of claims 1 to 9 for use in therapy.

12. A pharmaceutical composition which composes a compound according to any of claims 1 to 9 and a pharmaceutically acceptable carrier.

13. A compound according to claim 1 substantially as hereinbefore described with reference to any one of Examples 1 to 136.

14. A process for the preparation of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof substantially as hereinbefore described with reference to any one of Examples 1 to 136. - 113 - intellectual property office of nz 2 0 JUN 2001 RECEIVED END </div>