Patent Publication Number: US-2007099911-A1

Title: Pyrroloquinolinone derivatives as 5-hydroxytryptamine-6 ligands

Description:
This application claims the benefit under 35 U.S.C. §119(e) to co-pending U.S. provisional application No.60/731127, filed Oct. 28, 2005, which is hereby incorporated by reference in its entirety. 
    
    
     BACKGROUND OF THE INVENTION  
      Serotonin (5-hydroxytryptamine)(5-HT) receptors play a critical role in many physiological and behavioral functions in humans and animals. These functions are mediated through various 5-HT receptors distributed throughout the body. There are now approximately fifteen different human 5-HT receptor subtypes that have been cloned, many with well-defined roles in humans. The 5-HT6 receptor was first cloned from rat tissue in 1993 (Monsma et al.,  Molecular Pharmacology  1993, 43, 320-327) and subsequently from human tissue (Kohen et al.,  Journal of Neurochemistry  1996, 66, 47-56). The receptor is a G-protein coupled receptor (GPCR) positively coupled to adenylate cyclase (Ruat et al.,  Biochemical Biophysical Research Communications  1993, 193, 268-276). The receptor is found almost exclusively in the central nervous system (CNS) areas both in rat and in human. In situ hybridization studies of the 5-HT6 receptor in rat brain using mRNA indicate principal localization in the areas of 5-HT projection including striatum, nucleus accumbens, olfactory tubercle, and hippocampal formation (Ward et al.,  Neuroscience  1995, 64, 1105-1111).  
      There are many potential therapeutic uses for 5-HT6 ligands in humans based on direct effects and on indications from available scientific studies. These studies include the localization of the receptor, the affinity of ligands with known in vivo activity, and various animal studies conducted so far.  
      One potential therapeutic use of modulators of 5-HT6 receptor function is in the enhancement of cognition and memory in human diseases such as Alzheimer&#39;s Disease. The high levels of receptor found in important structures in the forebrain, including the caudate/putamen, hippocampus, nucleus accumbens, and cortex suggest a role for the receptor in memory and cognition, since these areas are known to play a vital role in memory (Gerard et al.,  Brain Research  1997, 746, 207-219). The ability of known 5-HT6 receptor ligands to enhance cholinergic transmission also supported the potential cognition use (Bentley et al.,  British Journal of Pharmacology  1999, 126(7), 1537-1542). Studies have found that a known 5-HT6 selective antagonist significantly increased glutamate and aspartate levels in the frontal cortex without elevating levels of noradrenaline, dopamine, or 5-HT. This selective elevation of neurochemicals known to be involved in memory and cognition strongly suggests a role for 5-HT6 ligands in cognition (Dawson et al.,  British Journal of Pharmacology  2000, 130(1), 23-26). Animal studies of memory and learning with a known selective 5-HT6 antagonist have found positive indications (Rogers et al.,  Society of Neuroscience, Abstracts  2000, 26, 680 and Foley et al.,  Neuropsychopharmacology  2004, 29(1), 93-100).  
      A related potential therapeutic use for 5-HT6 ligands is the treatment of attention deficit disorders (ADD, also known as Attention Deficit Hyperactivity Disorder or ADHD) in both children and adults. Because 5-HT6 antagonists appear to enhance the activity of the nigrostriatal dopamine pathway and because ADHD has been linked to abnormalities in the caudate (Ernst et al.,  Journal of Neuroscience  1998, 18(15), 5901-5907), 5-HT6 antagonists may attenuate attention deficit disorders.  
      Early studies examining the affinity of various CNS ligands with known therapeutic utility or a strong structural resemblance to known drugs suggests a role for 5-HT6 ligands in the treatment of schizophrenia and depression. For example, clozapine (an effective clinical antipsychotic) has high affinity for the 5-HT6 receptor subtype. Also, several clinical antidepressants have high affinity for the receptor as well and act as antagonists at this site (Branchek, et al.,  Annual Reviews in Pharmacology and Toxicology  2000, 40, 319-334).  
      Further, recent in vivo studies in rats indicate 5-HT6 modulators may be useful in the treatment of movement disorders including epilepsy (Stean et al.,  British Journal of Pharmacology  1999, 127 Proc. Supplement 131 P and Routledge et al.,  British Journal of Pharmacology  2000, 130(7), 1606-1612).  
      Taken together, the above studies strongly suggest that compounds which are 5-HT6 receptor modulators, i.e., ligands, may be useful for therapeutic indications including: the treatment of diseases associated with a deficit in memory, cognition, and learning such as Alzheimer&#39;s and attention deficit disorder; the treatment of personality disorders such as schizophrenia; the treatment of behavioral disorders, e.g., anxiety, depression and obsessive-compulsive disorders; the treatment of motion or motor disorders such as Parkinson&#39;s disease and epilepsy; the treatment of diseases associated with neurodegeneration such as stroke and head trauma; or withdrawal from drug addiction including addiction to nicotine, alcohol, and other substances of abuse.  
      Therefore, it is an object of this invention to provide compounds which are useful as therapeutic agents in the treatment of a variety of central nervous system disorders related to or affected by the 5-HT6 receptor.  
      It is another object of this invention to provide therapeutic methods and pharmaceutical compositions useful for the treatment of central nervous system disorders related to or affected by the 5-HT6 receptor.  
      It is a feature of this invention that the compounds provided may also be used to further study and elucidate the 5-HT6 receptor.  
     SUMMARY OF THE INVENTION  
      The present invention provides a pyrroloquinolinone compound of formula I  
                 
 
 wherein 
          X is N or CR 8 ;     n is an integer of 1, 2, 3, 4, 5, or 6;     R is H, SO 2 R 9  or an alkyl, cycloalkyl, alkenyl or alkynyl group each optionally substituted;     R 1  is H, halogen or an alkyl, aryl or heteroaryl group each optionally substituted;     R 2  and R 3  are each independently H or an optionally substituted alkyl group;     R 4  and R 5  are each independently H or an alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted, or R 4  and R 5  may be taken together with the atom to which they are attached to form an optionally substituted 5- to 8-membered ring optionally containing an additional heteroatom selected from O, S or NR 7 ;     R 6  and R 8  are each independently H, halogen or an alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;     R 7  is H or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, or heteroaryl group each optionally substituted; and     R 9  is an alkyl, aryl or heteroaryl group each optionally substituted; or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.       

    
    
      The present invention also provides methods and compositions useful in the treatment of central nervous system disorders.  
     DETAILED DESCRIPTION OF THE INVENTION  
      The 5-hydroxytryptamine-6 (5-HT6) receptor has been identified by molecular cloning. Its ability to bind a wide range of therapeutic compounds used in psychiatry, coupled with its intriguing distribution in the brain has stimulated significant interest in new compounds which are capable of interacting with or affecting said receptor. Significant efforts are being made to understand the possible role of the 5-HT6 receptor in psychiatry, cognitive dysfunction, motor function and control, memory, mood and the like. To that end, compounds which demonstrate a binding affinity for the 5-HT6 receptor are earnestly sought both as an aid in the study of the 5-HT6 receptor and as potential therapeutic agents in the treatment of central nervous system disorders, for example, see Reavill et al.,  Current Opinion in Investigational Drugs  2001, 2(1), 104-109.  
      Surprisingly, it has now been found that a pyrroloquinolinone compound of formula I demonstrates 5-HT6 affinity along with significant sub-type selectivity. Advantageously, said formula I compounds are effective therapeutic agents for the treatment of central nervous system (CNS) disorders associated with or affected by the 5-HT6 receptor. Accordingly, the present invention provides a pyrroloquinolinone compound of formula I  
                 
 
 wherein 
          X is N or CR 8 ;     n is an integer of 1, 2, 3, 4, 5, or 6;     R 1  is H, SO 2 R 9  or an alkyl, cycloalkyl, alkenyl or alkynyl group each optionally substituted;     R 1  is H, halogen or an alkyl, aryl or heteroaryl group each optionally substituted;     R 2  and R 3  are each independently H or an optionally substituted alkyl group;     R 4  and R 5  are each independently H or an alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted, or R 4  and R 5  may be taken together with the atom to which they are attached to form an optionally substituted 5- to 8-membered ring optionally containing an additional heteroatom selected from O, S or NR 7 ;     R 6  and R 8  are each independently H, halogen or an alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;     R 7  is H or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl, or heteroaryl group each optionally substituted; and     R 9  is an alkyl, aryl or heteroaryl group each optionally substituted; or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.        

      As used in the specification and claims, the term halogen designates F, Cl, Br or I and the term cycloheteroalkyl designates a five- to seven-membered cycloalkyl ring system containing 1 or 2 heteroatoms, which may be the same or different, selected from N, O or S and optionally containing one double bond. Exemplary of the cycloheteroalkyl ring systems included in the term as designated herein are the following rings wherein Y is NR′, O or S; and R′ is H or an optional substituent as described hereinbelow:  
                 
 
      Similarly, as used in the specification and claims, the term heteroaryl designates a five- to ten-membered aromatic ring system containing 1, 2 or 3 heteroatoms, which may be the same or different, selected from N, O or S. Such heteroaryl ring systems include pyridinyl, pyrrolyl, azolyl, oxazolyl, thiazolyl, imidazolyl, furyl, thienyl, quinolinyl, isoquinolinyl, indolyl, indazolyl, azaindazolyl, benzothienyl, benzofuranyl, benzisoxazolyl or the like. The term aryl designates a carbocyclic aromatic ring system, e.g. of 6 to 14 carbon atoms such as phenyl, naphthyl, anthracenyl or the like.  
      As used herein, the term “alkyl” as a group or part of a group eg alkoxy, alkylamino, alkylcarbonyl (=alkanoyl), includes both (C 1 -C 12 ) straight chain or branched-chain (unless defined otherwise) monovalent saturated hydrocarbon moiety. Examples of saturated hydrocarbon alkyl moieties include, but are not limited to, chemical groups of 1-6 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl; higher homologs such as n-pentyl, n-hexyl, and the like. Specifically included within the definition of “alkyl” are those alkyl groups that are optionally substituted. Suitable alkyl substitutions include, but are not limited to, CN, OH, halogen, phenyl, carbamoyl, carbonyl, alkoxy or aryloxy.  
      As used herein the term “haloalkyl” designates a C n H 2n+1 , group having from one to 2n+1 halogen atoms which may be the same or different. Examples of haloalkyl groups include CF 3 , CH 2 Cl, C 2 H 3 BrCl, C 3 H 5 F 2 , or the like.  
      The term “alkenyl”, as used herein, refers to either a (C 2 -C 10 ) straight chain or branched-chain monovalent hydrocarbon moiety containing at least one double bond. Such hydrocarbon alkenyl moieties may be mono or polyunsaturated, and may exist in the E or Z configurations. The compounds of this invention are meant to include all possible E and Z configurations. Examples of mono or polyunsaturated hydrocarbon alkenyl moieties include, but are not limited to, chemical groups such as vinyl, 2-propenyl, isopropenyl, crotyl, 2-isopentenyl, butadienyl, 2-(butadienyl), 2,4-pentadienyl, 3-(1,4-pentadienyl), and higher homologs, isomers, or the like.  
      The term “alkynyl”, as used herein, refers to either a (C 2 -C 10 ) straight chain or branched-chain monovalent hydrocarbon moiety containing at least one triple bond.  
      The term “cycloalkyl”, as used herein, refers to a monocyclic, bicyclic, tricyclic, fused, bridged, or spiro monovalent saturated hydrocarbon moiety of 3-10 carbon atoms, unless otherwise specified. Any suitable ring position of the cycloalkyl moiety may be covalently linked to the defined chemical structure. Examples of cycloalkyl moieties include, but are not limited to, chemical groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, adamantyl, spiro[4.5]decanyl, and homologs, isomers, or the like.  
      In the specification and claims, when the terms alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl are designated as being optionally substituted, the substituent groups which are optionally present may be one or more of those customarily employed in the development of pharmaceutical compounds, or the modification of such compounds, to influence their structure/activity, persistence, absorption, stability or other beneficial property. Specific examples of optional substituents include halogen atoms, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylaminocarbonyl, cycloalkyl, aryl, phenyl, phenoxy, benzyl, benzyloxy, heteroaryl, indolyl, heterocyclyl, (e.g., 5-10 membered heteroaryl or heterocycloalkyl moieties containing 1-3 ring heteroatoms selected from O, S and N) or cycloalkyl groups, preferably halogen atoms or lower alkyl or lower alkoxy groups where ‘lower’ denotes 1-6 carbon atoms. Typically, 0-3 substituents may be present. When any of the foregoing substituents represents or contains an alkyl substituent group, this may be linear or branched and may contain up to 12, preferably up to 6, more preferably up to 4 carbon atoms.  
      Pharmaceutically acceptable salts may be any acid addition salt formed by a compound of formula I and a pharmaceutically acceptable acid such as phosphoric, sulfuric, hydrochloric, hydrobromic, citric, maleic, malonic, mandelic, succinic, fumaric, acetic, lactic, nitric, sulfonic, p-toluene sulfonic, tartaric, malic, methane sulfonic acid or the like.  
      Compounds of the invention include esters, carbamates or other conventional prodrug forms, which in general, are functional derivatives of the compounds of the invention and which are readily converted to the inventive active moiety in vivo. Correspondingly, the method of the invention embraces the treatment of the various conditions described hereinabove with a compound of formula I or with a compound which is not specifically disclosed but which, upon administration, converts to a compound of formula I in vivo. Also included are metabolites of the compounds of the present invention defined as active species produced upon introduction of these compounds into a biological system.  
      Compounds of the invention may exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich or selectively prepare said stereoisomers. Accordingly, the present invention comprises compounds of formula I, the stereoisomers thereof and the pharmaceutically acceptable salts thereof. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active or enantiomerically pure form.  
      Preferred compounds of the invention are those compounds of formula I wherein n is 2. Also preferred are those compounds of formula I wherein R is H. Another group of preferred formula I compounds is those compounds wherein R 7  is H or an optionally substituted alkyl group.  
      More preferred compounds of the invention are those compounds of formula I wherein n is 2 and R 1  is H. Another group of more preferred compounds of the invention is those compounds of formula I wherein n is 2 and R 2  and R 3  are H. A further group of more preferred formula I compounds is those compounds wherein n is 2; R 2  and R 3  are H; and R 4  and R 5  are each independently H or alkyl.  
      Preferred compounds of the invention include: 
      1-(2-benzylaminoethyl)-6,7-dihydro-1H-pyrrolo[3,2-f]isoquinolin-6-one;     1-(2-aminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one;     1-(2-aminoethyl)-2-bromo-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one;     1-(2-aminoethyl)-7-methyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one;     1-(2-aminoethyl)-7-benzyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one;     1-(2-aminoethyl)-7-cyclohexylmethyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one;     1-(2-aminoethyl)-7-thien-3-ylmethyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one;     1-(2-aminoethyl)-7-(furan-2-ylmethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one;     1-(2-methylaminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one;     9-(2-aminoethyl)-3-benzyl-3H,7H-pyrrolo[2,3-h]quinazolin-4-one;     9-(2-aminoethyl)-3-methyl-3H,7H-pyrrolo[2,3-h]quinazolin-4-one;     9-(2-aminoethyl)-3-benzyl-3H,7H-pyrrolo[2,3-h]quinazolin-4-one;     9-(2-aminoethyl)-3H,7H-pyrrolo[2,3-h]quinazolin-4-one;     9-(2-aminoethyl)-2-(3-pyridinyl)-3H,7H-pyrrolo[2,3-h]quinazolin-4-one;     9-(2-aminoethyl)-2,3-dimethyl-3H,7H-pyrrolo[2,3-h]quinazolin-4-one;     a stereoisomer thereof; or a pharmaceutically acceptable salt thereof.    

      Compounds of formula I may be prepared using conventional synthetic methods and, if required, standard separation or isolation techniques. For example, compounds of formula I wherein R 4  and R 5  are H (Ia) may be prepared by reacting an isoquinolinone of formula II with a dioxolan derivative of formula III via a Fisher indole synthesis to obtain the desired compound of formula Ia. The formula Ia free amine may be reacted with an appropriate halide, R 4 -Hal, in the presence of a base such as NaH to give a compound of formula I wherein R 5  is H and R 4  is other than H (Ib). Similarly, the formula Ib compound may then be reacted with another halide, R 5 -Hal, in the presence of a base, to give the compound of formula I wherein R 4  and R 5  are other than H (Ic). The reactions are shown in flow diagram I wherein Hal is Cl, Br or I.  
                 
 
      Alternatively, compounds of formula Ib may be obtained using a two-step reaction sequence involving, the reaction of la with a carboxylic acid derivative to provide the corresponding amide and subsequent reduction of said amide with a suitable reducing agent, such as LiAlH 4 , to give the desired amine of formula Ib. This process may be repeated with an alternative carboxylic acid derivative with subsequent reduction to provide the fully substituted amine derivative of formula Ic.  
      A method useful for preparing libraries of compounds of formula Ib or Ic is the reaction of formula Ia with a suitable aldehyde derivative to form the corresponding imine and reducing said imine with a suitable reducing agent such as NaBH 4 , or for ease of automation, polymer supported borohydride, to give a compound of formula Ib in high yield.  
      Isoquinolinones or quinazolinones of formula II are known and are commercially available or may be prepared, e.g., by the methods described by Izumi et al.,  J. Heterocyclic Chem.  1990, 27,1419, and Hegedus et al.,  J. Org. Chem.  1977, 42,1329. For example, 4-fluoro-2-ethenyl substituted benzamides of formula IV can be intramolecularly cyclized to the corresponding isoquinolinone or quinazolinone by the combined action of palladium(II)chloride and copper(I)chloride to give the fluoroisoquinolinone or fluoroquinazolinoneof formula V and reacting said formula V compound with hydrazine to give the desired compound of formula II. The reaction is shown in flow diagram II.  
                 
 
      Compounds of formula V wherein X is CH may also be prepared by the method described by Heck et al. in J. Org. Chem., 1977, 42, 3903 and J. Org. Chem., 1978, 43, 2454. Compounds of formula V wherein X is N (Va) may be prepared by the cyclocondensation reaction of anthranilic acid derivatives, i.e. Rewcastle et al.,  J. Med. Chem.  1996, 39(4), 918-928, Hudson et al. (WO 96/09294), Houghten et al., (WO 98/11438), Fantin et al.,  J. Org. Chem.  1993, 58(3), 741-743, or Bhattacharya et al. (WO 97/28118, WO 97/28132 and WO 97/28134). Compounds of formula Va may also be prepared by the reaction of 2-amino-4-fluorobenzoic acid with a formamidine acetate derivative of formula VI, followed by the reaction of the formula VI compound with an electrophile, R 7 -Hal, in the presence of a base to give the desired compound of formula Va. The reaction is shown in flow diagram III wherein Hal is Cl, Br or I.  
                 
 
      Compounds of formula V are then converted, via reaction with hydrazine as shown in flow diagram II, to compounds of formula II and the formula II compounds are then used to prepare compounds of formula I as shown in flow diagram I hereinabove.  
      Advantageously, the formula I compounds of the invention are useful for the treatment of CNS disorders relating to or affected by the 5-HT6 receptor including mood, personality, behavioral, psychiatric, cognitive, neurodegenerative, or the like disorders, for example, Alzheimer&#39;s disease, Parkinson&#39;s disease, attention deficit disorder, anxiety, epilepsy, depression, obsessive-compulsive disorder, sleep disorders, neurodegenerative disorders (such as head trauma or stroke), feeding disorders (such as anorexia or bulimia), schizophrenia, memory loss, disorders associated with withdrawal from drug or nicotine abuse, or the like or certain gastrointestinal disorders such as irritable bowel syndrome. Accordingly, the present invention provides a method for the treatment of a disorder of the central nervous system related to or affected by the 5-HT6 receptor in a patient in need thereof which comprises providing said patient a therapeutically effective amount of a compound of formula I as described hereinabove. The compounds may be provided by oral or parenteral administration or in any common manner known to be an effective administration of a therapeutic agent to a patient in need thereof.  
      The term “providing” as used herein with respect to providing a compound or substance embraced by the invention, designates either directly administering such a compound or substance, or administering a prodrug, derivative or analog which forms an equivalent amount of the compound or substance within the body. The therapeutically effective amount provided in the treatment of a specific CNS disorder may vary according to the specific condition(s) being treated, the size, age and response pattern of the patient, the severity of the disorder, the judgment of the attending physician or the like. In general, effective amounts for daily oral administration may be about 0.01 to 1,000 mg/kg, preferably about 0.5 to 500 mg/kg and effective amounts for parenteral administration may be about 0.1 to 100 mg/kg, preferably about 0.5 to 50 mg/kg.  
      In actual practice, the compounds of the invention are provided by administering the compound or a precursor thereof in a solid or liquid form, either neat or in combination with one or more conventional pharmaceutical carriers or excipients. Accordingly, the present invention provides a pharmaceutical composition which comprises a pharmaceutically acceptable carrier and an effective amount of a compound of formula I as described hereinabove.  
      Solid carriers suitable for use in the composition of the invention include one or more substances which may also act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, glidants, compression aides, binders, tablet-disintegrating agents or encapsulating materials. In powders, the carrier may be a finely divided solid which is in admixture with a finely divided compound of formula I. In tablets, the formula I compound may be mixed with a carrier having the necessary compression properties in suitable proportions and compacted in the shape and size desired. Said powders and tablets may contain up to 99% by weight of the formula I compound. Solid carriers suitable for use in the composition of the invention include calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins.  
      Any pharmaceutically acceptable liquid carrier suitable for preparing solutions, suspensions, emulsions, syrups and elixirs may be employed in the composition of the invention. Compounds of formula I may be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, or a pharmaceutically acceptable oil or fat, or a mixture thereof. Said liquid composition may contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, coloring agents, viscosity regulators, stabilizers, osmo-regulators, or the like. Examples of liquid carriers suitable for oral and parenteral administration include water (particularly containing additives as above, e.g., cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols, e.g., glycols) or their derivatives, or oils (e.g., fractionated coconut oil and arachis oil). For parenteral administration the carrier may also be an oily ester such as ethyl oleate or isopropyl myristate.  
      Compositions of the invention which are sterile solutions or suspensions are suitable for intramuscular, intraperitoneal or subcutaneous injection. Sterile solutions may also be administered intravenously. Inventive compositions suitable for oral administration may be in either liquid or solid composition form.  
      For a more clear understanding, and in order to illustrate the invention more clearly, specific examples thereof are set forth hereinbelow. The following examples are merely illustrative and are not to be understood as limiting the scope and underlying principles of the invention in any way.  
      Unless otherwise stated, all parts are parts by weight. The term NMR designates nuclear magnetic resonance. The terms THF, DMF and EtOAc designate tetrahydrofuran, dimethyl formamide and ethyl acetate, respectively.  
     EXAMPLE 1  
     4-Fluorocinnamyl azide  
      An acetone solution (25 ml) of 4-fluorocinnamic acid (2.0 g, 12.0 mmol) and triethylamine (1.27 g, 12.6 mmol) was cooled to −20° C. under nitrogen and the stirred mixture was treated with ethyl chloroformate (1.76 g, 16.2 mmol). After two hours, an aqueous solution of sodium azide (1.09 g, 16.8 mmol in 5 mL) was added, and the reaction mixture was stirred for a further two hours. The mixture was filtered and concentrated to dryness to provide the acylazide as a white crystalline solid (2.2 g, 95% yield).  
      Elemental Analysis for: C 9 H 6 FN 3 O Calculated: C, 56.55; H, 3.16; N, 21.98 Found: C, 56.65; H, 3.19; N, 22.01  
     EXAMPLE 2  
     6-Fluoro-1-isoquinolinone  
      A solution of 4-fluorocinnamylazide from Example 1 (10.0 g, 52.6 mmol) in diphenyl ether (90 ml), containing a crystal of iodine, was heated at 320° C. for fifteen minutes. The mixture was cooled to ambient temperature, diluted with hexane (900 ml) and the precipitated product (6.1 g, 71% yield) was collected by filtration. The product was crystallized from acetone to afford a white solid.  
      Elemental Analysis for: C 9 H 6 FNO Calculated: C, 66.26; H, 3.71; N, 8.59 Found: C, 66.45; H, 3.92; N, 8.66  
     EXAMPLE 3  
     6-Hydrazino-1-isoquinolinone  
      A solution of 6-fluoro-1-isoquinolinone (11.5 g, 70.5 mmol) from Example 2 and hydrazine (56.4 g, 1.76 mol) was refluxed in dioxane (175 ml) under nitrogen for 19 hours. The mixture was concentrated under vacuo, 200 ml of water added thereto, and the product collected by filtration. An ethanolic solution (500 ml) of the product was treated with 50 ml of 2N HCl, and the solution was filtered and concentrated in vacuo to afford the required product as a light yellow colored solid (12.8 g, 86% yield, mp 270° C.).  
      Elemental Analysis for: C 9 H 9 N 3 O 1.0 HCl Calculated: C, 51.07; H, 4.76; N, 19.85 Found: C, 50.41; H, 4.91; N, 19.33  
     EXAMPLE 4  
     1-(2-Aminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 6-hydrazino-1-isoquinolinone (1.0 g, 4.73 mmol) from Example 3 and 2-(3-chloropropyl)-1,3 dioxolan (1.32 g, 8.9 mmol) in degassed ethanol (80 ml)/water (15 ml) was refluxed under nitrogen for one hour. The reaction mixture was concentrated in vacuo, and the product was purified by flash silica gel chromatography to afford an amber colored solid (0.45 g, 42% yield). Treatment of the product with ethereal HCl and crystallization from ethanol-ether gave the mono hydrochloride salt as a light amber colored solid (mp &gt;280° C.).  
      Elemental Analysis for: C 13 H 13 N 3 O, 1.0 HCl 0.3 H 2 O Calculated: C, 58.02; H, 5.47; N, 15.61 Found: C, 57.92; H, 5.38; N, 15.20  
     EXAMPLE 5  
     1-(2-Aminoethyl)-2-bromo-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      Bromine (1.27 mmol) was added to a stirred solution of 1-(2-aminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one (0.240 g, 1.06 mmol) from Example 4 in DMF (2 ml). After three hours, the solution was concentrated to dryness, and the product was purified by crystallization from ethereal ethanol. Two further recrystallizations from the same solvent system provided the titled compound as a white solid (0.114 g, 27% yield, mp 252° C., decomposes).  
      Elemental Analysis for: C 13 H 12 BrN 3 O 1.0 HBr Calculated: C, 40.34; H, 3.39; N, 10.89 Found: C, 40.58; H, 3.54; N, 10.46  
     EXAMPLE 6  
     1-(2-N-Benzoylaminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of benzoyl chloride (0.928 g, 6.6 mmol) in methylene chloride (10 ml) was added dropwise to a stirred aqueous solution of 1-(2-aminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one (0.75 g, 3.3 mmol in 10 ml) from Example 4 containing potassium carbonate (0.684 g, 4.95 mmol). After one hour, the mixture was concentrated under vacuum, and the product was purified by flash silica gel chromatography (eluting with 5% MeOH/CH 2 Cl 2 ) to afford the required product as a light brown solid.  
     EXAMPLE 7A  
     1-(2-Benzylaminoethyl)-6,7-dihydro-1H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of the amide (0.47 g, 1.4 mmol) from Example 6 in THF (5 ml) was treated with an excess of borane THF (1M, 20 mmol) at room temperature under nitrogen, and the mixture was stirred for 30 hours. The reaction was terminated by the addition of HCl, and the product isolated by flash silica gel chromatography (20% MeOH/5% NH 4 OH/75% CH 2 Cl 2 ) to afford a clear solid. Treatment with ethanolic HCl afforded the salt of the titled compound as a white solid. (mp 210° C.).  
      Elemental Analysis for: C 20 H 19 N 3 O 1.0 HCl Calculated: C, 67.89; H, 5.70; N, 11.87 Found: C,,67.95; H, 5.67; N, 11.98  
     EXAMPLE 7B  
     Library Procedure  
     1-(2-Benzylaminoethyl)-6,7-dihydro-1H-pyrrolo[3,2-f]isoquinolin-6-one  
      Molecular sieves (100 mg), benzaldehyde (100 μL), and 500 μL of a 0.1 M solution of the HCl salt of 1-(2-aminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one (from Example 4) in anhydrous methanol (containing two equivalents of triethylamine) was shaken for 24 hours. Borohydride resin (57 mg) was added to the reaction well, and the mixture shaken for 16 hours at room temperature. Methanol (1 ml) was added, the mixture vortexed, and the top solution removed and concentrated. The product was dissolved in DMSO (1.6 ml), and the product purity confirmed by HPLC and MS analysis.  
      C 20 H 19 N 3 O (MW 317.39)  
     EXAMPLES 8-91  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table I were obtained and identified by HPLC and mass spectral analyses.  
               TABLE I                                                                                      Ex.               No.   R4   Mass                                 8   naphth-2-ylmethyl   367.45       9   4-phenoxybenzyl   409.48       10   ethyl   255.31       11   2-chlorobenzyl   351.83       12   furfur-2-ylmethyl   307.35       13   4-dimethylaminobenzyl   360.45       14   thiophen-2-ylmethyl   323.41       15   4-methylbenzyl   331.41       16   4-chlorobenzyl   351.83       17   4-cyanobenzyl   342.40       18   n-pentyl   297.40       19   3,4-methylenedioxybenzyl   361.40       20   4-isopropylbenzyl   359.47       21   5-methylfurfur-2-ylmethyl   321.37       22   4-hydroxybenzyl   333.38       23   4-methoxybenzyl   347.41       24   2-methoxybenzyl   347.41       25   3-fluoro-4-methoxybenzyl   365.40       26   3,5-bis(trifluoromethyl)benzyl   453.38       27   2,6-difluorobenzyl   353.37       28   2-fluorobenzyl   335.38       29   2-trifluoromethylbenzyl   385.38       30   3-trifluoromethylbenzyl   385.38       31   4-trifluoromethylbenzyl   385.38       32   3-fluorobenzyl   335.38       33   4-fluorobenzyl   335.38       34   indol-3-ylmethyl   356.42       35   furfur-3-ylmethyl   307.35       36   thiophen-3-ylmethyl   323.41       37   pyridin-3-ylmethyl   318.37       38   2-methylbenzyl   331.41       39   3-chlorobenzyl   351.83       40   3-methylbutyl   297.40       41   3-methoxybenzyl   347.41       42   4-trifluoromethoxybenzyl   401.38       43   pyridin-4-ylmethyl   318.37       44   2,4-dichlorobenzyl   386.28       45   pyridin-2-ylmethyl   318.37       46   6-methyl-pyridin-2-ylmethyl   332.40       47   4-bromobenzyl   396.28       48   1-methylpyrrol-2-ylmethyl   320.39       49   2,4-difluorobenzyl   353.37       50   4-carbomethoxybenzyl   375.42       51   cyclohexylmethyl   323.43       52   4-phenylbenzyl   393.48       53   4-thiomethylbenzyl   363.48       54   4-ethylbenzyl   345.44       55   quinolin-2-ylmethyl   368.43       56   4-n-propyloxybenzyl   375.47       57   (S)-(−)-3,7-dimethyloct-6-enyl   365.51       58   3,4-dichlorobenzyl   386.28       59   2,4-dimethylbenzyl   345.44       60   1,4-benzodioxan-6-ylmethyl   375.42       61   3,5-difluorobenzyl   353.37       62   3,4-difluorobenzyl   353.37       63   2-chloro-4-hydroxybenzyl   367.83       64   2-fluoro-3-trifluoromethylbenzyl   403.37       65   3-trifluoromethoxybenzyl   401.38       66   3-bromo-4-methoxybenzyl   426.31       67   3-methylbenzyl   331.41       68   3-bromobenzyl   396.28       69   3,5-dimethoxybenzyl   377.44       70   2-chloro-4-fluorobenzyl   369.82       71   5-chloro-thiophen-2-ylmethyl   357.86       72   2-bromobenzyl   396.28       73   benzofuran-2-ylmethyl   357.41       74   5-bromo-furan-2-ylmethyl   386.24       75   4-diethylaminobenzyl   388.51       76   6-chloro-3,4-methylenedioxybenzyl   396.84       77   3-bromo-4-fluorobenzyl   414.27       78   3-chloro-4-fluorobenzyl   369.82       79   3,5-dichlorobenzyl   386.28       80   4-n-hexyloxybenzyl   417.55       81   trans-4-stilbene-2-yl-methyl   419.52       82   (R)-(+)-3,7-dimethyloct-6-enyl   365.51       83   2-carboethoxy-cycloprop-1-ylmethyl   353.42       84   2,3-dihydrobenzo[b]furan-5-ylmethyl   359.42       85   5-bromothiophen-2-ylmethyl   402.31       86   3-(3,4-dichlorophenoxy)benzyl   478.37       87   3-nitrobenzyl   362.38       88   3,4,5-trihydroxy-n-pentyl   345.39       89   3-cyanobenzyl   342.40       90   4(5)-imidazolylmethyl   307.35       91   3-hydroxybenzyl   333.38                  
 
     EXAMPLE 92  
     2-N-methyl-6-fluoro-1-isoquinolinone  
      A stirred solution of 6-fluoro-1-isoquinolinone (3.1 g, 19.0 mmol from Example 2) and sodium hydride (0.684 g, 28.5 mmol) in DMF (40 ml) was treated with methyl iodide (4.05 g, 28.5 mmol) at −30° C. After stirring under nitrogen at ambient temperature for 30 minutes, 50 ml of 1N aqueous HCl was added thereto, and the product was extracted into CH 2 C1 2  (3×50 ml). The combined organic layers were washed with 50 ml of water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a solid. This was crystallized from hexane/CH 2 C1 2  to afford the titled product as a white solid (3.0 g, 89% yield).  
      Elemental Analysis for: C 10 H 8 FNO Calculated: C, 7.79; H, 4.55; N, 7.91 Found: C, 67.95; H, 4.67; N, 7.98  
     EXAMPLE 93  
     2-N-methyl-6-hydrazino-1-isoquinolinone  
      A stirred solution of 2-N-methyl-6-fluoro-1-isoquinolinone (3.0 g, 16.9 mmol from Example 92) and hydrazine (5 g, 0.156 mmol) was refluxed in 50 ml of dioxane under nitrogen for 19 hours. The mixture was concentrated under vacuo, 50 ml of water was added thereto and the product collected by filtration. An ethanolic solution of the product (100 ml) was treated with 2N HCl (10 ml), filtered and concentrated in vacuo to afford the required product as a light yellow colored solid (3.1 g, 81% yield).  
      Elemental Analysis for: C 10 H 11 N 3 O 1.0 HCl Calculated: C, 53.22; H, 5.36; N, 18.62 Found: C, 53.51; H, 5.45; N, 18.69  
     EXAMPLE 94  
     1-(2-aminoethyl-7-methyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-methyl-6-hydrazino-1-isoquinolinone (1.0 g, 4.4 mmol, from Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan (0.89 g, 5.94 mmol) according to the process outlined in Example 4. After refluxing for 3.5 hours, the product was isolated in the manner described in Example 4 and purified by flash silica gel chromatography (20% MeOH, 5% NH 4 0H in CH 2 Cl 2 ) to afford a light brown oil (0.584 g, 55% yield). Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt which was crystallized twice from EtOH/Et 2 O to afford the product as a light tan colored solid (mp 295-298° C.).  
      Elemental Analysis for: C 14 H 15 N 3 O 1.0 HCl 0.6H 2 O Calculated: C, 58.27; H, 6.01; N, 14.56 Found: C, 58.11; H, 5.99; N, 14.43  
     EXAMPLE 95  
     7-methyl-1-(2-phenethylaminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of phenacetyl chloride (0.58 g, 3.8 mmol) in methylene chloride (10 ml) was added dropwise to a stirred aqueous solution of 1-(2-aminoethyl)-7-methyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one (0.60 g, 2.5 mmol in 10 ml) from Example 94 containing triethylamine (0.51 g, 5 mmol). After one hour, the mixture was concentrated under vacuum, and the product was purified by flash silica gel chromatography (eluting with 3% MeOH/EtOAc) to afford the required product as a cream colored solid (0.56 g, 63% yield). A solution of the amide (1.53 mmol) in THF (5 ml) was treated with an excess of borane-THF (1M, 9 mmol) at room temperature under nitrogen, and the mixture was stirred for 30 hours. The reaction was terminated by the addition of HCl, and the product was isolated by flash silica gel chromatography (10% MeOH/5% NH 4 OH/85% CH 2 Cl 2 ) to afford a light brown colored solid (0.24 g, 45% yield). Treatment with ethanolic HCl afforded the salt of the titled compound as an off white colored solid (mp 205-208° C.).  
      Elemental Analysis for: C 22 H 23 N 3 O 1.0 HCl Calculated: C, 69.19; H, 6.33; N, 11.00 Found: C, 69.25; H, 6.47; N, 11.08  
     EXAMPLE 96  
     7-methyl-1-(2-benzylaminoethyl)-3H,7H-pyrrolo[3.2-f]isoquinolin-6-one  
      A solution of benzoic anhydride (1.7 g, 7.9 mmol) in DMF (10 ml) was added dropwise to a stirred solution of 1-(2-aminoethyl)-7-methyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one (1.2 g, 4.97 mmol in 10 ml DMF) from Example 94 containing triethylamine (0.80 g, 7.9 mmol). After one hour, the mixture was concentrated under vacuum and the product purified by flash silica gel chromatography (eluting with 5% MeOH/CH 2 Cl 2 ) to afford the required product as an off white colored solid (0.95 g, 55% yield). A solution of the amide (2.61 mmol) in THF (30 ml) was treated with an excess of borane-THF (1M, 10.4 mmol) at room temperature under nitrogen, and the mixture was refluxed for two hours. The reaction was terminated by the addition of concentrated HCl, and the product isolated by chromatography (10% MeOH/5% NH 4 OH/85% CH 2 Cl 2 , on A1203) to afford a tan colored solid (21% yield). Treatment with ethanolic HCl afforded the salt of the titled compound as a white solid (mp 186-192° C.).  
      Elemental Analysis for: C 21 H 21 N 3 O 1.0 HCl Calculated: C, 68.56; H, 6.03; N, 11.42 Found: C, 68.75; H, 6.17; N, 11.58  
     EXAMPLE 97  
     1-(2-dimethylaminoethyl)-7-methyl-3H,7H-pyrrolo[3,2-]isoquinolin-6-one  
      A solution of 1-(2-aminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one (0.2 g, 0.88 mmol from Example 4) in DMF (2 mL) was treated with sodium hydroxide (2.5 N, 0.2 mmol) and methyl iodide (2.1 mmol), and the mixture was stirred at room temperature for 3 days. The product was purified by flash silica gel chromatography (50% MeOH, 5% NH 4 OH in CH 2 Cl 2 ) to afford the titled compound which was treated with ethereal HCl to afford the required salt as a white solid (0.26 mmol, 30% yield, mp 180° C.).  
      Elemental Analysis for: C 16 H 19 N 3 O 1.0 HCl Calculated: C, 62.84; H, 6.59; N, 13.74 Found: C, 62.85; H, 6.67; N,13.87  
     EXAMPLES 98-181  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-methyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde. The compounds shown in Table II were obtained and identified by HPLC and mass spectral analyses.  
               TABLE II                                                                                      Ex.               No.   R4   Mass                                 98   naphth-2-ylmethyl   381.47       99   4-phenoxybenzyl   423.51       100   ethyl   269.34       101   2-chlorobenzyl   365.86       102   furfur-2-ylmethyl   321.37       103   4-dimethylaminobenzyl   374.48       104   thiophen-2-ylmethyl   337.44       105   4-methylbenzyl   345.44       106   4-chlorobenzyl   365.86       107   4-cyanobenzyl   356.42       108   n-pentyl   311.42       109   3,4-methylenedioxybenzyl   375.42       110   4-isopropylbenzyl   373.49       111   5-methylfurfur-2-ylmethyl   335.40       112   4-hydroxybenzyl   347.41       113   4-methoxybenzyl   361.44       114   2-methoxybenzyl   361.44       115   3-fluoro-4-methoxybenzyl   379.43       116   3,5-bis(trifluoromethyl)benzyl   467.41       117   2,6-difluorobenzyl   367.39       118   2-fluorobenzyl   349.40       119   2-trifluoromethylbenzyl   399.41       120   3-trifluoromethylbenzyl   399.41       121   4-trifluoromethylbenzyl   399.41       122   3-fluorobenzyl   349.40       123   4-fluorobenzyl   349.40       124   indol-3-ylmethyl   370.45       125   furfur-3-ylmethyl   321.37       126   thiophen-3-ylmethyl   337.44       127   pyridin-3-ylmethyl   332.40       128   2-methylbenzyl   345.44       129   3-chlorobenzyl   365.86       130   3-methylbutyl   311.42       131   3-methoxybenzyl   361.44       132   4-trifluoromethoxybenzyl   415.41       133   pyridin-4-ylmethyl   332.40       134   2,4-dichlorobenzyl   400.30       135   pyridin-2-ylmethyl   332.40       136   6-methyl-pyridin-2-ylmethyl   346.43       137   4-bromobenzyl   410.31       138   1-methylpyrrol-2-ylmethyl   334.42       139   2,4-difluorobenzyl   367.39       140   4-carbomethoxybenzyl   389.45       141   cyclohexylmethyl   337.46       142   4-phenylbenzyl   407.51       143   4-thiomethylbenzyl   377.51       144   4-ethylbenzyl   359.47       145   quinolin-2-ylmethyl   382.46       146   4-n-propyloxybenzyl   389.49       147   (S)-(−)-3,7-dimethyloct-6-enyl   379.54       148   3,4-dichlorobenzyl   400.30       149   2,4-dimethylbenzyl   359.47       150   1,4-benzodioxan-6-ylmethyl   389.45       151   3,5-difluorobenzyl   367.39       152   3,4-difluorobenzyl   367.39       153   2-chloro-4-hydroxybenzyl   381.86       154   2-fluoro-3-trifluoromethylbenzyl   417.40       155   3-trifluoromethoxybenzyl   415.41       156   3-bromo-4-methoxybenzyl   440.33       157   3-methylbenzyl   345.44       158   3-bromobenzyl   410.31       159   3,5-dimethoxybenzyl   391.46       160   2-chloro-4-fluorobenzyl   383.85       161   5-chloro-thiophen-2-ylmethyl   371.89       162   2-bromobenzyl   410.31       163   benzofuran-2-ylmethyl   371.43       164   5-bromo-furan-2-ylmethyl   400.27       165   4-diethylaminobenzyl   402.53       166   6-chloro-3,4-methylenedioxybenzyl   409.87       167   3-bromo-4-fluorobenzyl   428.30       168   3-chloro-4-fluorobenzyl   383.85       169   3,5-dichlorobenzyl   400.30       170   4-n-hexyloxybenzyl   431.57       171   trans-4-stilbene-2-yl-methyl   433.55       172   (R)-(+)-3,7-dimethyloct-6-enyl   379.54       173   2-carboethoxy-cyclopropyl-1-ylmethyl   367.44       174   2,3-dihydrobenzo[b]furan-5-ylmethyl   373.45       175   5-bromothiophen-2-ylmethyl   416.34       176   3-(3,4-dichlorophenoxy)benzyl   492.40       177   3-nitrobenzyl   376.41       178   3,4,5-trihydroxy-n-pentyl   359.42       179   3-cyanobenzyl   356.42       180   4(5)-imidazolylmethyl   321.38       181   3-hydroxybenzyl   347.41                  
 
     EXAMPLE 182  
     1-2-aminoethyl)-7-benzyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-benzyl-6-hydrazino-1-isoquinolinone (0.5 g, 1.66 mmol, prepared from benzyl bromide in 66% yield according to Examples 92 and 93 was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan (0.34 g, 2.24 mmol) according to the process outlined in Example 4. After refluxing for four hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH, 5% NH 4 OH in CH 2 Cl 2 ) to afford a light brown oil. Treatment with ethanolic HCl gave the required product (0.162 g, 27% yield) as its mono hydrochloride salt as an off white colored solid (mp 266-268° C.).  
      Elemental Analysis for: C 20 H 19 N 3 O 1.0 HCl 1.3H 2 O calculated: C 63.67; H, 6.04; N, 11.14 Found: C,  63 . 59 ; H, 6.04; N, 11.01  
     EXAMPLE 183  
     1-2-aminoethyl)-7-benzyl-3-methyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 1-(2-aminoethyl)-7-benzyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one (0.25 g, 0.79 mmol) from Example 182 and methyl iodide (0.135 g, 0.95 mmol) in DMF (2 ml) was treated with sodium hydride (0.022 g, 0.91 mmol), and the resulting mixture was stirred at 0° C. under nitrogen for one hour. Water (10 ml) was added and the product extracted with ethyl acetate (2×15 ml). The combined organics were washed with 15 ml of brine, separated and dried over anhydrous sodium sulfate. Filtration and concentration in vacuo gave a light brown colored solid (0.21 g). The product was purified by flash silica gel chromatography (10% MeOH/5% NH4OH in CH 2 Cl 2 ) to afford a white solid. Treatment with ethanolic HCl gave the titled compound as its mono hydrochloride salt as a white solid (0.138 g, 48% yield, mp 172-176° C.).  
      Elemental Analysis for: C 21 H 21 N 3 O 1.0 HCl 1H 2 O Calculated: C, 65.36; H, 6.27; N, 10.89 Found: C, 65.16; H, 6.04; N, 10.52  
     EXAMPLES 184-267  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-benzyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table III were obtained and identified by HPLC and mass spectral analyses.  
               TABLE III                                                                                      Ex.               No.   R4   Mass                                 184   naphth-2-ylmethyl   457.57       185   4-phenoxybenzyl   499.61       186   ethyl   345.44       187   2-chlorobenzyl   441.95       188   furfur-2-ylmethyl   397.47       189   4-dimethylaminobenzyl   450.58       190   thiophen-2-ylmethyl   413.54       191   4-methylbenzyl   421.54       192   4-chlorobenzyl   441.95       193   4-cyanobenzyl   432.59       194   n-pentyl   387.52       195   3,4-methylenedioxybenzyl   451.52       196   4-isopropylbenzyl   449.59       197   5-methylfurfur-2-ylmethyl   441.5       198   4-hydroxybenzyl   423.51       199   4-methoxybenzyl   437.54       200   2-methoxybenzyl   437.54       201   3-fluoro-4-methoxybenzyl   455.53       202   3,5-bis(trifluoromethyl)benzyl   543.51       203   2,6-difluorobenzyl   443.49       204   2-fluorobenzyl   425.50       205   2-trifluoromethylbenzyl   475.51       206   3-trifluoromethylbenzyl   475.51       207   4-trifluoromethylbenzyl   475.51       208   3-fluorobenzyl   425.50       209   4-fluorobenzyl   425.50       210   indol-3-ylmethyl   446.55       211   furfur-3-ylmethyl   397.47       212   thiophen-3-ylmethyl   413.54       213   pyridin-3-ylmethyl   408.50       214   2-methylbenzyl   421.54       215   3-chlorobenzyl   441.95       216   3-methylbutyl   387.52       217   3-methoxybenzyl   437.54       218   4-trifluoromethoxybenzyl   491.51       219   pyridin-4-ylmethyl   408.50       220   2,4-dichlorobenzyl   476.40       221   pyridin-2-ylmethyl   408.50       222   6-methyl-pyridin-2-ylmethyl   422.52       223   4-bromobenzyl   486.41       224   1-methylpyrrol-2-ylmethyl   410.51       225   2,4-difluorobenzyl   443.49       226   4-carbomethoxybenzyl   465.55       227   cyclohexylmethyl   413.56       228   4-phenylbenzyl   483.61       229   4-thiomethylbenzyl   453.60       230   4-ethylbenzyl   435.56       231   quinolin-2-ylmethyl   458.56       232   4-n-propyloxybenzyl   465.59       233   (S)-(−)-3,7-dimethyloct-6-enyl   455.64       234   3,4-dichlorobenzyl   476.40       235   2,4-dimethylbenzyl   435.56       236   1,4-benzodioxan-6-ylmethyl   465.55       237   3,5-difluorobenzyl   443.49       238   3,4-difluorobenzyl   443.49       239   2-chloro-4-hydroxybenzyl   457.95       240   2-fluoro-3-trifluoromethylbenzyl   493.50       241   3-trifluoromethoxybenzyl   491.51       242   3-bromo-4-methoxybenzyl   516.43       243   3-methylbenzyl   421.54       244   3-bromobenzyl   486.41       245   3,5-dimethoxybenzyl   467.56       246   2-chloro-4-fluorobenzyl   459.95       247   5-chloro-thiophen-2-ylmethyl   447.98       248   2-bromobenzyl   486.41       249   benzofuran-2-ylmethyl   447.53       250   5-bromo-furan-2-ylmethyl   476.37       251   4-diethylaminobenzyl   478.63       252   6-chloro-3,4-methylenedioxybenzyl   485.96       253   3-bromo-4-fluorobenzyl   504.40       254   3-chloro-4-fluorobenzyl   459.95       255   3,5-dichlorobenzyl   476.40       256   4-n-hexyloxybenzyl   507.67       257   trans-4-stilbene-2-yl-methyl   509.65       258   (R)-(+)-3,7-dimethyloct-6-enyl   455.64       259   2-carboethoxy-cycloprop-1-ylmethyl   443.54       260   2,3-dihydrobenzo[b]furan-5-ylmethyl   449.55       261   5-bromothiophen-2-ylmethyl   492.43       262   3-(3,4-dichlorophenoxy)benzyl   568.50       263   3-nitrobenzyl   452.51       264   3,4,5-trihydroxy-n-pentyl   435.52       265   3-cyanobenzyl   432.52       266   4(5)-imidazolylmethyl   397.47       267   3-hydroxybenzyl   423.51                  
 
     EXAMPLE 268  
     1-(3-aminopropyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 6-hydrazino-1-isoquinolinone (1.0 g, 4.73 mmol) from Example 3 and 2-(4-chlorobutyl)-1,3-dioxolan (1.05 g, 6.39 mmol) in degassed ethanol (80 ml)/water (16 ml) was refluxed under nitrogen for five hours. The reaction mixture was concentrated in vacuo and the product purified by flash silica gel chromatography (20% MeOH/5% NH 4 OH in CH 2 Cl 2 ) to afford a light amber colored solid (0.08 g, 7% yield). Treatment of the product with ethereal HCl and crystallization from ethanol ether gave the mono hydrochloride salt of the titled compound as a light tan colored solid (mp 225-230° C.).  
      Elemental Analysis for: C 14 H 15 N 3 O 1.0 HCl Calculated: C, 60.54; H, 5.81; N, 15.13 Found: C, 60.65; H, 5.87; N, 15.19  
     EXAMPLE 269  
     1-(2-aminoethyl)-7-cyclohexylmethyl-3H,7H-pyrrolo[3,2-]isoquinolin-6-one  
      A solution of 2-N-cyclohexylmethyl-6-hydrazino-1-isoquinolinone (1.0 g, 3.2 mmol, prepared from cyclohexylmethylbromide in 69% yield according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan (0.651 g, 4.32 mmol) in a mixture of degassed ethanol (80 ml) and water (20 ml) according to the process outlined in Example 4. After refluxing for three hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH/5% NH 4 OH in CH 2 Cl 2 ) to afford a viscous brown oil (0.8 g). Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt which was crystallized twice from EtOH/Et 2 O to afford the product as a light brown colored solid (0.33 g, 28% yield, mp 220-224° C.).  
      Elemental Analysis for: C 20 H 25 N 3 O 1.0 HCl 1.5H 2 O Calculated: C, 62.09; H, 7.55; N, 10.86 Found: C, 62.32; H, 7.27; N, 10.56  
     EXAMPLE 270  
     1-(2-aminoethyl)-7-phenylethyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-phenylethyl-6-hydrazino-1-isoquinolinone (1.0 g, 3.2 mmol, prepared from 2-phenylethylbromide in 72% yield in the manner described in Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan (0.65 g, 4.3 mmol) in a mixture of degassed ethanol (80 ml) and water (20 ml) according to the process outlined in Example 4. After refluxing for three hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH/5% NH 4 OH in CH 2 Cl 2 ) to afford a light brown colored solid (0.37 g). Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt which was crystallized twice from EtOH/Et 2 O to afford the product as a white solid (0.36 g, 31% yield, mp 162-166° C.).  
      Elemental Analysis for: C 21 H 21 N 3 O 1.0 HCl 1.75H 2 O Calculated: C, 63.15; H, 6.43; N, 10.52 Found: C, 63.47; H, 6.14; N, 10.52  
     EXAMPLE 271  
     1-(2-aminoethyl)-7-naphthalen-2-ylmethyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-naphthalen-2-ylmethyl-6-hydrazino-1-isoquinolinone (2.25 g, 6.40 mmol, prepared from naphthalen-2-ylmethylbromide in 59% yield according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan (1.3 g, 8.64 mmol) in degassed ethanol (130 ml)/water (90 ml) according to the process outlined in Example 4. After refluxing for three hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH/5% NH 4 OH in CH 2 Cl 2 ) to afford an off white colored solid (0.43 g, 18% yield). Treatment with ethanolic HCl gave the titled product as its mono hydrochloride salt which was crystallized from EtOH/Et 2 O to afford an off white colored solid (0.43 g, mp 288-292° C.).  
      Elemental Analysis for: C 24 H 21 N 30  1.0 HCl 0.25 H 2 O Calculated: C, 70.58; H, 5.55; N, 10.29 Found: C, 70.64; H, 5.62; N, 10.17  
     EXAMPLE 272  
     1-(2-aminoethyl)-7-heptyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-heptyl-6-hydrazino-1-isoquinolinone (0.95 g, 3.07 mmol, prepared from heptylbromide in 72% yield according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan (0.623 g, 4.14 mmol) in degassed ethanol (80 ml)/water (20 ml) according to the process outlined in Example 4. After refluxing for 3.5 hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH/5% NH 4 OH in CH 2 Cl 2 ) to afford an off white colored solid (0.33 g, 33% yield). Treatment with ethanolic HCl gave the titled product as its mono hydrochloride salt which was crystallized from EtOH/Et 2 O to afford a white solid (0.33 g, mp 239-241° C.).  
      Elemental Analysis for: C 20 H 27 N 30  1.0 HCl Calculated: C, 66.37; H, 7.80; N, 11.61 Found: C, 65.95; H, 7.51; N, 11.64  
     EXAMPLE 273  
     1-(2-aminoethyl)-7-(34-dichlorobenzyl)-3H,7H-pyrrolo[3.2-f]isoquinolin-6-one  
      A solution of 2-N-(3,4-dichlorobenzyl)-6-hydrazino-1-isoquinolinone (1.30 g, 3.51 mmol, prepared from 3,4-dichlorobenzyl bromide in 79% yield according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan (0.80 g, 5.31 mmol) in a mixture of degassed ethanol (100ml) and water (25 ml) according to the process outlined in Example 4. After refluxing for three hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH/5% NH 4 OH in CH 2 Cl 2 ) to afford a light yellow colored solid (0.395 g). Treatment with ethanolic HCl gave the titled product as its mono hydrochloride salt which was crystallized from EtOH/Et 2 O to afford a white solid (0.37 g, 27% yield, mp 188-190° C.).  
      Elemental Analysis for: C 20 H 17 N 3 OCl   2  1.0 HCl 1H 2 O Calculated: C, 54.50; H, 4.57; N, 9.53 Found: C, 54.76; H, 4.36; N, 9.31  
     EXAMPLE 274  
     1-(2-aminoethyl)-7-thiophen-3-ylmethyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-(thiophen-3-ylmethyl)-6-hydrazino-1-isoquinolinone (0.5 g, 1.62 mmol, prepared from thiophen-3-ylmethyl bromide in 64% yield according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan (0.33 g, 2.19 mmol) in a mixture of degassed ethanol (40 ml) and water (8 ml) according to the process outlined in Example 4. After refluxing for four hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH/5% NH 4 OH in CH 2 Cl 2 ) to afford a yellow colored solid (0.17 g, 32% yield). Treatment with ethanolic HCl gave the titled product as its mono hydrochloride salt which was crystallized from EtOH/Et 2 O to afford a light yellow colored solid (0.17 g, mp 260-264° C.).  
      Elemental Analysis for: CB 8 H 17 N 3 OS 1.0 HCl 1.1H 2 O Calculated: C, 56.94; H, 5.36; N, 11.07 Found: C, 56.63; H, 5.30; N, 10.66  
     EXAMPLE 275  
     3-methyl-6-fluoro-1-isoquinolinone  
      A suspension of 4-fluoro-2-isopropenylbenzamide (2.50 g, 14 mmol), palladium (II) chloride (0.248 g, 1.4 mmol) and copper (I) chloride (1.386 g, 14 mmol) in DME (25 ml) was stirred under nitrogen at 60° C. for 24 hours. The mixture was cooled, filtered and concentrated in vacuo. The product was purified by crystallization twice from acetone to afford a white solid (1.3 g, 52% yield).  
      Elemental Analysis for: C 10 H 8 FNO Calculated: C, 67.79; H, 4.55; N, 7.91 Found: C, 68.01; H, 4.67; N, 8.10  
     EXAMPLE 276  
     3-methyl-6-hydrazino-1-isoquinolinone  
      The titled compound was obtained as a light yellow colored solid in 84% yield from 3-methyl-6-fluoro-1-isoquinolinone using the procedure described in Example 3.  
      Elemental Analysis for: C 10 H 11 N 3 O 1.0 HCl Calculated: C, 53.22; H, 5.36; N, 18.62 Found: C, 53.54; H, 5.46; N, 18.80  
     EXAMPLE 277  
     1-(2-aminoethyl)-8-methyl-3H,7H-pyrrolo[3.2-f]isoquinolin-6-one  
      A solution of 3-methyl-6-hydrazino-1-isoquinolinone (1.0 g, 5.2 mmol) and 2-(3-chloropropyl)-1,3-dioxolan (1.32 g, 8.9 mmol) in a mixture of degassed ethanol (80 ml) and water (15 ml) was refluxed under nitrogen for four hours. The reaction mixture was concentrated in vacuo and the product purified by flash silica gel chromatography to afford an amber colored solid (0.71 g, 56% yield). Treatment of the product with ethereal HCl and crystallization from ethanol ether gave the mono hydrochloride salt as a light amber colored solid (m.p. &gt;200° C.).  
      Elemental Analysis for: C 14 H 15 N 3 O 1.0 HCl Calculated: C, 60.54; H, 5.81; N, 15.13 Found: C, 60.45; H, 5.88; N, 15.20  
     EXAMPLE 278  
     1-(2-aminoethyl)-2-(4-chlorophenyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 6-hydrazino-1-isoquinolinone (1.0 g, 4.73 mmol) from Example 3 and 4,4′-dichlorobutyrophenone (1.39 g, 6.4 mmol, 1.35 equivalents) in degassed ethanol (50 ml)/water (50 ml) was refluxed under nitrogen for six hours. The reaction mixture was concentrated in vacuo, and the product was purified by flash silica gel chromatography to afford a yellow colored solid (0.21 g, 13% yield). Treatment of the product with methanolic HCl and crystallization from ethanol ether gave the hydrochloride salt as a light tan colored solid (mp &gt;300° C.).  
      Elemental Analysis for: C 19 H 16 ClN 3 O 2.0 HCl Calculated: C, 55.56; H, 4.42; N, 10.23 Found: C, 55.63; H, 4.56; N, 10.20  
     EXAMPLE 279  
     1-(2-aminoethyl)-9-chloro-3H,7H-pyrrolo[3.2-f]isoquinolin-6-one  
      A solution of 4-chloro-6-hydrazino-1-isoquinolinone (0.51 g, 2.07 mmol) and 2-(3-chloropropyl)-1,3-dioxolan (0.39 g, 2.59 mmol, 1.25 equivalents) in degassed ethanol (40 ml)/water (8 ml) was refluxed under nitrogen for four hours. The reaction mixture was concentrated in vacuo and the product purified by flash silica gel chromatography to afford a light brown colored solid (0.16 g, 29% yield). Treatment of the product with methanolic HCl and crystallization from ethanol ether gave the mono hydrochloride salt as a light tan colored solid (mp 239-243° C.).  
      Elemental Analysis for: C 13 H 12 ClN 3 O 1.0 HCl Calculated: C, 52.37; H, 4.39; N, 14.39 Found: C, 52.48; H, 4.56; N, 14.55  
     EXAMPLE 280  
     1-(2-aminoethyl)-7-ethyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-ethyl-6-hydrazino-1-isoquinolinone (0.45 g, 1.88 mmol, prepared from iodoethane by the method described in Example 92 and Example 93) in degassed ethanol (40 ml)/water (8 ml) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan (0.354 g, 2.35 mmol, 1.25 equivalents) according to the process outlined in Example 4. After refluxing for 4 hours, the product was isolated in the manner described in Example 4 and purified by chromatography (neutral alumina, type III, eluting with 4% MeOH in CH 2 Cl 2 ) to afford a light yellow oil (0.105 g, 22% yield). Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt which was crystallized from EtOH/Et 2 O to afford the product as a white solid (mp 224-227° C.).  
      Elemental Analysis for: C 15 H 17 N 3 O 1.0 HCl Calculated: C, 61.75; H, 6.22; N, 14.40 Found: C, 61.95; H, 6.49; N, 14.43  
     EXAMPLES 281-288  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-ethyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table IV were obtained and identified by HPLC and mass spectral analyses.  
               TABLE IV                                                                                      Ex. No.   R4   Mass               281   3-nitrobenzyl   390.44       282   3,4,5-trihydroxy-n-pentyl   373.45       283   3-chlorobenzyl   379.88       284   3-methoxybenzyl   375.47       285   pyridin-4-ylmethyl   346.43       286   3-cyanobenzyl   370.45       287   4(5)-imidazolylmethyl   335.40       288   3-hydroxybenzyl   361.44                  
 
     EXAMPLE 289  
     1-(2-aminoethyl)-7-(tetrahydropyran-2-ylmethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-(tetrahydropyran-2-ylmethyl)-6-hydrazinoisoquinolinone (0.70 g, 2.26 mmol, prepared from tetrahydropyran-2-ylmethylbromide by the method described in Example 92 and Example 93) in degassed ethanol (55 ml)/water (10 ml) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan (0.426 g, 2.83 mmol, 1.25 equivalents) according to the process outlined in Example 4. After refluxing for 4 hours, the product was isolated in the manner described in Example 4, and purified by chromatography (neutral alumina, type III, eluting with 5% MeOH in CH 2 Cl 2 ) to afford a yellow colored solid (0.251 g, 34% yield). Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt which was crystallized from EtOH/Et 2 O to afford the product as a white solid (mp 260-262° C.). Elemental Analysis for: C 19 H 23 N 3 O 2  1.0 HCl Calculated: C, 63.06; H, 6.68; N, 11.61 Found: C, 63.25; H, 6.69; N, 11.63  
     EXAMPLE 290  
     1-(2-aminoethyl)-7-(2-methoxyethyl)-3H,7H-pyrrolo[3.2-f]isoquinolin-6-one  
      A solution of 2-N-(2-methoxyethyl)-6-hydrazinoisoquinolinone (1.37 g, 5.87 mmol, prepared from 1-bromo-2-methoxyethane by the method described in Example 92 and Example 93) in degassed ethanol (100 ml)/water (16 ml) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan (1.11 g, 7.34 mmol, 1.25 equivalents) according to the process outlined in Example 4. After refluxing for 4 hours, the product was isolated in the manner described in Example 4 and purified by chromatography (silica gel, eluting with 8% MeOH in CH 2 Cl 2 ) to afford a yellow colored solid (0.200 g, 12% yield). Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt which was crystallized from EtOH/Et 2 O to afford the product as a white solid (mp 246-249° C.).  
      Elemental Analysis for: C 16 H 19 N 3 O 2  1.0 HCl Calculated: C, 59.72; H, 6.26; N, 13.06 Found: C, 59.92; H, 6.39; N, 13.23  
     EXAMPLE 291  
     1-(2-aminoethyl)-7-(4-fluorobenzyl)-3H,7H-Pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-(4-fluorobenzyl)-6-hydrazinoisoquinolinone (0.88 g, 3.10 mmol, prepared from 4-fluorobenzylbromide by the method described in Example 92 and Example 93) in degassed ethanol (100 ml)/water (16 ml) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan (0.46 g, 3.1 mmol) according to the process outlined in Example 4. After refluxing for 16 hours, the product was isolated in the manner described in Example 4 and purified by chromatography (silica gel, eluting with 10% MeOH inCH 2 Cl 2 ) to afford a yellow colored solid (0.45 g). Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt as a pale yellow colored solid (mp 247-249° C.).  
      Elemental Analysis for: C 20 H 18 FN 3 O 1.0 HCl Calculated: C, 64.60; H, 5.15; N, 11.30 Found: C, 64.72; H, 5.39; N, 11.33  
     EXAMPLES 292-376  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-(4-fluorobenzyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table V were obtained and identified by HPLC and mass spectral analyses.  
               TABLE V                                                                                      Ex.               No.   R4   Mass               292   naphth-2-ylmethyl   475.56       293   4-phenoxybenzyl   517.60       294   ethyl   363.43       295   2-chlorobenzyl   459.95       296   furfur-2-ylmethyl   415.46       297   4-dimethylaminobenzyl   468.57       298   benzyl   425.50       299   thiophen-2-ylmethyl   431.53       300   4-methylbenzyl   439.53       301   4-chlorobenzyl   459.95       302   4-cyanobenzyl   450.51       303   n-pentyl   405.51       304   3,4-methylenedioxybenzyl   469.51       305   4-isopropylbenzyl   467.58       306   5-methylfurfur-2-ylmethyl   429.49       307   4-hydroxybenzyl   441.50       308   4-methoxybenzyl   455.53       309   2-methoxybenzyl   455.53       310   3-fluoro-4-methoxybenzyl   473.52       311   3,5-bis(trifluoromethyl)benzyl   561.50       312   2,6-difluorobenzyl   461.48       313   2-fluorobenzyl   443.49       314   2-trifluoromethylbenzyl   493.50       315   3-trifluoromethylbenzyl   493.50       316   4-trifluoromethylbenzyl   493.50       317   3-fluorobenzyl   443.49       318   4-fluorobenzyl   443.49       319   indol-3-ylmethyl   464.54       320   furfur-3-ylmethyl   415.46       321   thiophen-3-ylmethyl   431.53       322   pyridin-3-ylmethyl   426.49       323   2-methylbenzyl   439.53       324   3-chlorobenzyl   459.95       325   3-methylbutyl   405.51       326   3-methoxybenzyl   455.53       327   4-trifluoromethoxybenzyl   509.50       328   pyridin-4-ylmethyl   426.49       329   2,4-dichlorobenzyl   494.39       330   pyridin-2-ylmethyl   426.49       331   6-methyl-pyridin-2-ylmethyl   440.52       332   4-bromobenzyl   504.40       333   1-methylpyrrol-2-ylmethyl   428.50       334   2,4-difluorobenzyl   461.48       335   4-carbomethoxybenzyl   483.54       336   cyclohexylmethyl   431.55       337   4-phenylbenzyl   401.60       338   4-thiomethylbenzyl   471.59       339   4-ethylbenzyl   453.55       340   quinolin-2-ylmethyl   476.55       341   4-n-propyloxybenzyl   483.58       342   (S)-(-)-3,7-dimethyloct-6-enyl   473.63       343   3,4-dichlorobenzyl   494.39       344   2,4-dimethylbenzyl   453.55       345   1,4-benzodioxan-6-ylmethyl   483.54       346   3,5-difluorobenzyl   461.48       347   3,4-difluorobenzyl   461.48       348   2-chloro-4-hydroxybenzyl   475.94       349   2-fluoro-3-trifluoromethylbenzyl   511.49       350   3-trifluoromethoxybenzyl   509.50       351   3-bromo-4-methoxybenzyl   534.42       352   3-methylbenzyl   539.55       353   3-bromobenzyl   504.40       354   3,5-dimethoxybenzyl   485.55       355   2-chloro-4-fluorobenzyl   477.94       356   5-chloro-thiophen-2-ylmethyl   465.97       357   2-bromobenzyl   504.40       358   benzofuran-2-ylmethyl   465.52       359   5-bromo-furan-2-ylmethyl   494.36       360   4-diethylaminobenzyl   496.62       361   6-chloro-3,4-methylenedioxybenzyl   503.96       362   3-bromo-4-fluorobenzyl   522.39       363   3-chloro-4-fluorobenzyl   477.94       364   3,5-dichlorobenzyl   494.39       365   4-n-hexyloxybenzyl   525.66       366   trans-4-stilbene-2-yl-methyl   527.64       367   (R)-(+)-3,7-dimethyloct-6-enyl   473.63       368   2-carboethoxy-cycloprop-1-ylmethyl   461.53       369   2,3-dihydrobenzo[b]furan-5-ylmethyl   467.54       370   5-bromothiophen-2-ylmethyl   510.42       371   3-(3,4-dichlorophenoxy)benzyl   586.49       372   3-nitrobenzyl   470.50       373   3,4,5-trihydroxy-n-pentyl   453.51       374   3-cyanobenzyl   450.51       375   4(5)-imidazolylmethyl   415.47       376   3-hydroxybenzyl   441.50                  
 
     
       
         
           
               
             
               
                 TABLE V 
               
             
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
            
               
                 Ex. 
                   
                   
               
               
                 No. 
                 R4 
                 Mass 
               
               
                   
               
               
                 313 
                 2-fluorobenzyl 
                 443.49 
               
               
                 314 
                 2-trifluoromethylbenzyl 
                 493.50 
               
               
                 315 
                 3-trifluoromethylbenzyl 
                 493.50 
               
               
                 316 
                 4-trifluoromethylbenzyl 
                 493.50 
               
               
                 317 
                 3-fluorobenzyl 
                 443.49 
               
               
                 318 
                 4-fluorobenzyl 
                 443.49 
               
               
                 319 
                 indol-3-ylmethyl 
                 464.54 
               
               
                 320 
                 furfur-3-ylmethyl 
                 415.46 
               
               
                 321 
                 thiophen-3-ylmethyl 
                 431.53 
               
               
                 322 
                 pyridin-3-ylmethyl 
                 426.49 
               
               
                 323 
                 2-methylbenzyl 
                 439.53 
               
               
                 324 
                 3-chlorobenzyl 
                 459.95 
               
               
                 325 
                 3-methylbutyl 
                 405.51 
               
               
                 326 
                 3-methoxybenzyl 
                 455.53 
               
               
                 327 
                 4-trifluoromethoxybenzyl 
                 509.50 
               
               
                 328 
                 pyridin-4-ylmethyl 
                 426.49 
               
               
                 329 
                 2,4-dichlorobenzyl 
                 494.39 
               
               
                 330 
                 pyridin-2-ylmethyl 
                 426.49 
               
               
                 331 
                 6-methyl-pyridin-2-ylmethyl 
                 440.52 
               
               
                 332 
                 4-bromobenzyl 
                 504.40 
               
               
                 333 
                 1-methylpyrrol-2-ylmethyl 
                 428.50 
               
               
                 334 
                 2,4-difluorobenzyl 
                 461.48 
               
               
                 335 
                 4-carbomethoxybenzyl 
                 483.54 
               
               
                 336 
                 cyclohexylmethyl 
                 431.55 
               
               
                 337 
                 4-phenylbenzyl 
                 401.60 
               
               
                 338 
                 4-thiomethylbenzyl 
                 471.59 
               
               
                 339 
                 4-ethylbenzyl 
                 453.55 
               
               
                 340 
                 quinolin-2-ylmethyl 
                 476.55 
               
               
                 341 
                 4-n-propyloxybenzyl 
                 483.58 
               
               
                 342 
                 (S)-(−)-3,7-dimethyloct-6-enyl 
                 473.63 
               
               
                 343 
                 3,4-dichlorobenzyl 
                 494.39 
               
               
                 344 
                 2,4-dimethylbenzyl 
                 453.55 
               
               
                 345 
                 1,4-benzodioxan-6-ylmethyl 
                 483.54 
               
               
                 346 
                 3,5-difluorobenzyl 
                 461.48 
               
               
                 347 
                 3,4-difluorobenzyl 
                 461.48 
               
               
                 348 
                 2-chloro-4-hydroxybenzyl 
                 475.94 
               
               
                 349 
                 2-fluoro-3-trifluoromethylbenzyl 
                 511.49 
               
               
                 350 
                 3-trifluoromethoxybenzyl 
                 509.50 
               
               
                 351 
                 3-bromo-4-methoxybenzyl 
                 534.42 
               
               
                 352 
                 3-methylbenzyl 
                 539.55 
               
               
                 353 
                 3-bromobenzyl 
                 504.40 
               
               
                 354 
                 3,5-dimethoxybenzyl 
                 485.55 
               
               
                 355 
                 2-chloro-4-fluorobenzyl 
                 477.94 
               
               
                 356 
                 5-chloro-thiophen-2-ylmethyl 
                 465.97 
               
               
                 357 
                 2-bromobenzyl 
                 504.40 
               
               
                 358 
                 benzofuran-2-ylmethyl 
                 465.52 
               
               
                 359 
                 5-bromo-furan-2-ylmethyl 
                 494.36 
               
               
                 360 
                 4-diethylaminobenzyl 
                 496.62 
               
               
                 361 
                 6-chloro-3,4-methylenedioxybenzyl 
                 503.96 
               
               
                 362 
                 3-bromo-4-fluorobenzyl 
                 522.39 
               
               
                 363 
                 3-chloro-4-fluorobenzyl 
                 477.94 
               
               
                 364 
                 3,5-dichlorobenzyl 
                 494.39 
               
               
                 365 
                 4-n-hexyloxybenzyl 
                 525.66 
               
               
                 366 
                 trans-4-stilbene-2-yl-methyl 
                 527.64 
               
               
                 367 
                 (R)-(+)-3,7-dimethyloct-6-enyl 
                 473.63 
               
               
                 368 
                 2-carboethoxy-cycloprop-1-ylmethyl 
                 461.53 
               
               
                 369 
                 2,3-dihydrobenzo[b]furan-5-ylmethyl 
                 467.54 
               
               
                 370 
                 5-bromothiophen-2-ylmethyl 
                 510.42 
               
               
                 371 
                 3-(3,4-dichlorophenoxy)benzyl 
                 586.49 
               
               
                 372 
                 3-nitrobenzyl 
                 470.50 
               
               
                 373 
                 3,4,5-trihydroxy-n-pentyl 
                 453.51 
               
               
                 374 
                 3-cyanobenzyl 
                 450.51 
               
               
                 375 
                 4(5)-imidazolylmethyl 
                 415.47 
               
               
                 376 
                 3-hydroxybenzyl 
                 441.50 
               
               
                   
               
            
           
         
       
     
     EXAMPLE 377  
     1-(2-aminoethyl)-7-(2-fluorobenzyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-(2-fluorobenzyl)-6-hydrazinoisoquinolinone (0.95 g, 3.35 mmol, prepared from 2-fluorobenzylbromide by the method described in Example 92 and Example 93) in degassed ethanol (100 ml)/water (16 ml) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan (0.5 g, 3.35 mmol) according to the process outlined in Example 4. After refluxing for 16 hours, the product was isolated in the manner described in Example 4 and purified by chromatography (silica gel, eluting with 10% MeOH in CH 2 Cl 2 ) to afford a yellow colored solid (0.47 g). Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt as a pale yellow colored solid (mp &gt;250° C.).  
      Elemental Analysis for: C 20 H 18 FN 3 O 1.0 HCl Calculated: C, 64.60; H, 5.15; N, 11.30 Found: C, 64.79; H, 5.27; N, 11.42  
     EXAMPLES 378-462  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-(2-fluorobenzyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table VI were obtained and identified by HPLC and mass spectral analyses.  
               TABLE VI                                                                                      Ex.               No.   R4   Mass               378   naphth-2-ylmethyl   475.56       379   4-phenoxybenzyl   517.60       380   ethyl   363.43       381   2-chlorobenzyl   459.95       382   furfur-2-ylmethyl   415.46       383   4-dimethylaminobenzyl   468.57       384   benzyl   425.50       385   thiophen-2-ylmethyl   431.53       386   4-methylbenzyl   439.53       387   4-chlorobenzyl   459.95       388   4-cyanobenzyl   450.51       389   n-pentyl   405.51       390   3,4-methylenedioxybenzyl   469.51       391   4-isopropylbenzyl   467.58       392   5-methylfurfur-2-ylmethyl   429.49       393   4-hydroxybenzyl   441.50       394   4-methoxybenzyl   455.53       395   2-methoxybenzyl   455.53       396   3-fluoro-4-methoxybenzyl   473.52       397   3,5-bis(trifluoromethyl)benzyl   561.50       398   2,6-difluorobenzyl   461.48       399   2-fluorobenzyl   443.49       400   2-trifluoromethylbenzyl   493.50       401   3-trifluoromethylbenzyl   493.50       402   4-trifluoromethylbenzyl   493.50       403   3-fluorobenzyl   443.49       404   4-fluorobenzyl   443.49       405   indol-3-ylmethyl   464.54       406   furfur-3-ylmethyl   415.46       407   thiophen-3-ylmethyl   431.53       408   pyridin-3-ylmethyl   426.49       409   2-methylbenzyl   439.53       410   3-chlorobenzyl   459.95       411   3-methylbutyl   405.51       412   3-methoxybenzyl   455.53       413   4-trifluoromethoxybenzyl   509.50       414   pyridin-4-ylmethyl   426.49       415   2,4-dichlorobenzyl   494.39       416   pyridin-2-ylmethyl   426.49       417   6-methyl-pyridin-2-ylmethyl   440.52       418   4-bromobenzyl   504.40       419   1-methylpyrrol-2-ylmethyl   428.50       420   2,4-difluorobenzyl   461.48       421   4-carbomethoxybenzyl   483.54       422   cyclohexylmethyl   431.55       423   4-phenylbenzyl   401.60       424   4-thiomethylbenzyl   471.59       425   4-ethylbenzyl   453.55       426   quinolin-2-ylmethyl   476.55       427   4-n-propyloxybenzyl   483.58       428   (S)-(−)-3,7-dimethyloct-6-enyl   473.63       429   3,4-dichlorobenzyl   494.39       430   2,4-dimethylbenzyl   453.55       431   1,4-benzodioxan-6-ylmethyl   483.54       432   3,5-difluorobenzyl   461.48       433   3,4-difluorobenzyl   461.48       434   2-chloro-4-hydroxybenzyl   475.94       435   2-fluoro-3-trifluoromethylbenzyl   511.49       436   3-trifluoromethoxybenzyl   509.50       437   3-bromo-4-methoxybenzyl   534.42       438   3-methylbenzyl   539.55       439   3-bromobenzyl   504.40       440   3,5-dimethoxybenzyl   485.55       441   2-chloro-4-fluorobenzyl   477.94       442   5-chloro-thiophen-2-ylmethyl   465.97       443   2-bromobenzyl   504.40       444   benzofuran-2-ylmethyl   465.52       445   5-bromo-furan-2-ylmethyl   494.36       446   4-diethylaminobenzyl   496.62       447   6-chloro-3,4-methylenedioxybenzyl   503.96       448   3-bromo-4-fluorobenzyl   522.39       449   3-chloro-4-fluorobenzyl   477.94       450   3,5-dichlorobenzyl   494.39       451   4-n-hexyloxybenzyl   525.66       452   trans-4-stilbene-2-yl-methyl   527.64       453   (R)-(+)-3,7-dimethyloct-6-enyl   473.63       454   2-carboethoxy-cycloprop-1-ylmethyl   461.53       455   2,3-dihydrobenzo[b]furan-5-ylmethyl   467.54       456   5-bromothiophen-2-ylmethyl   510.42       457   3-(3,4-dichlorophenoxy)benzyl   586.49       458   3-nitrobenzyl   470.50       459   3,4,5-trihydroxy-n-pentyl   453.51       460   3-cyanobenzyl   450.51       461   4(5)-imidazolylmethyl   415.47       462   3-hydroxybenzyl   441.50                  
 
     EXAMPLE 463  
     1-(2-aminoethyl)-7-thiophen-2-ylmethyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-(thiophen-2-ylmethyl)-6-hydrazino-1-isoquinolinone (prepared from 2-thienyl bromide according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan according to the process outlined in Example 4. After refluxing for four hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH, 5% NH 4 OH in CH 2 Cl 2 ) to afford a light brown oil. Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt as an off white colored solid, MW=359.87; HPLC single component;identified by HNMR.  
      Elemental Analysis for: C 18 H 17 N 3 OS 1.0 HCl Calculated: C, 64.07; H, 5.04; N, 11.68 Found: C, 64.09; H, 5.07; N, 11.72  
     EXAMPLES 464-548  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-(thiophen-2-ylmethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table VII were obtained and identified by HPLC and mass spectral analyses.  
               TABLE VII                                                                                      Ex.               No.   R4   Mass               464   naphthyl-2-ylmethyl   463.60       465   4-phenoxybenzyl   505.64       466   ethyl   351.47       467   2-chlorobenzyl   447.98       468   furfur-2-ylmethyl   403.50       469   4-dimethylaminobenzyl   456.61       470   benzyl   413.54       471   thiophen-2-ylmethyl   419.57       472   4-methylbenzyl   427.57       473   4-chlorobenzyl   447.98       474   4-cyanobenzyl   438.55       475   n-pentyl   393.55       476   3,4-methylenedioxybenzyl   457.55       477   4-isopropylbenzyl   455.62       478   5-methylfurfur-2-ylmethyl   417.53       479   4-hydroxybenzyl   429.54       480   4-methoxybenzyl   443.56       481   2-methoxybenzyl   443.56       482   3-fluoro-4-methoxybenzyl   461.56       483   3,5-bis(trifluoromethyl)benzyl   549.53       484   2,6-difluorobenzyl   449.52       485   2-fluorobenzyl   431.53       486   2-trifluoromethylbenzyl   481.54       487   3-trifluoromethylbenzyl   481.54       488   4-trifluoromethylbenzyl   481.54       489   3-fluorobenzyl   431.53       490   4-fluorobenzyl   431.53       491   indol-3-ylmethyl   452.57       492   furfur-3-ylmethyl   403.50       493   thiophen-3-ylmethyl   419.57       494   pyridin-3-ylmethyl   414.53       495   2-methylbenzyl   427.57       496   3-chlorobenzyl   447.98       497   3-methylbutyl   393.55       498   3-methoxybenzyl   443.56       499   4-trifluoromethoxybenzyl   497.54       500   pyridin-4-ylmethyl   414.53       501   2,4-dichlorobenzyl   482.43       502   pyridin-2-ylmethyl   414.53       503   6-methyl-pyridin-2-ylmethyl   428.55       504   4-bromobenzyl   492.43       505   1-methylpyrrol-2-ylmethyl   416.54       506   2,4-difluorobenzyl   449.52       507   4-carbomethoxybenzyl   471.57       508   cyclohexylmethyl   419.59       509   4-phenylbenzyl   489.64       510   4-thiomethylbenzyl   459.63       511   4-ethylbenzyl   441.59       512   quinolin-2-ylmethyl   464.59       513   4-n-propyloxybenzyl   471.62       514   (S)-(−)-3,7-dimethyloct-6-enyl   461.67       515   3,4-dichlorobenzyl   482.43       516   2,4-dimethylbenzyl   441.59       517   1,4-benzodioxan-6-ylmethyl   471.57       518   3,5-difluorobenzyl   449.52       519   3,4-difluorobenzyl   449.52       520   2-chloro-4-hydroxybenzyl   463.98       521   2-fluoro-3-trifluoromethylbenzyl   499.53       522   3-trifluoromethoxybenzyl   497.54       523   3-bromo-4-methoxybenzyl   522.46       524   3-methylbenzyl   427.57       525   3-bromobenzyl   492.43       526   3,5-dimethoxybenzyl   473.59       527   2-chloro-4-fluorobenzyl   465.97       528   5-chloro-thiophen-2-ylmethyl   454.01       529   2-bromobenzyl   492.43       530   benzofuran-2-ylmethyl   453.56       531   5-bromo-furan-2-ylmethyl.   482.40       532   4-diethylaminobenzyl   484.66       533   6-chloro-3,4-methylenedioxybenzyl   491.99       534   3-bromo-4-fluorobenzyl   510.42       535   3-chloro-4-fluorobenzyl   565.97       536   3,5-dichlorobenzyl   482.43       537   4-n-hexyloxybenzyl   513.70       538   trans-4-stilbene-2-yl-methyl   515.67       539   (R)-(+)-3,7-dimethyloct-6-enyl   461.67       540   2-carboethoxy-cycloprop-1-ylmethyl   449.57       541   2,3-dihydrobenzo[b]furan-5-ylmethyl   455.58       542   5-bromothiophen-2-ylmethyl   498.46       543   3-(3,4-dichlorophenoxy)benzyl   574.52       544   3-nitrobenzyl   458.54       545   3,4,5-trihydroxy-n-pentyl   441.55       546   3-cyanobenzyl   438.55       547   4(5)-imidazolylmethyl   403.50       548   3-hydroxybenzyl   429.54                  
 
     EXAMPLE 549  
     1-(2-aminoethyl)-7-cyclopropylmethyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-cyclopropylmethyl-6-hydrazino-1-isoquinolinone (prepared from bromomethylcyclopropane according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan according to the process outlined in Example 4. After refluxing for four hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH, 5% NH 4 OH in CH 2 Cl 2 ) to afford a light brown oil. Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt as an off white colored solid (MW=317.81; HPLC single component; 1H-NMR, 3.9 δ, 2H, d).  
      Elemental Analysis for: C 17 H 19 N 3 O 1.0 HCl Calculated: C, 64.25; H, 6.34; N, 13.22 Found: C, 64.49; H, 6.47; N, 13.42  
     EXAMPLES 550-634  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-cyclopropylmethyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table VII were obtained and identified by HPLC and mass spectral analyses.  
               TABLE VIII                                                                                      Ex.               No.   R4   Mass               550   naphth-2-ylmethyl   421.54       551   4-phenoxybenzyl   463.57       552   ethyl   309.41       553   2-chlorobenzyl   405.92       554   furfur-2-ylmethyl   361.44       555   4-dimethylaminobenzyl   414.55       556   benzyl   371.48       557   thiophen-2-ylmethyl   377.51       558   4-methylbenzyl   385.50       559   4-chlorobenzyl   405.92       560   4-cyanobenzyl   396.49       561   n-pentyl   351.49       562   3,4-methylenedioxybenzyl   415.49       563   4-isopropylbenzyl   413.56       564   5-methylfurfur-2-ylmethyl   375.47       565   4-hydroxybenzyl   387.48       566   4-methoxybenzyl   401.50       567   2-methoxybenzyl   401.50       568   3-fluoro-4-methoxybenzyl   419.49       569   3,5-bis(trifluoromethyl)benzyl   507.47       570   2,6-difluorobenzyl   407.46       571   2-fluorobenzyl   389.47       572   2-trifluoromethylbenzyl   439.48       573   3-trifluoromethylbenzyl   439.48       574   4-trifluoromethylbenzyl   439.48       575   3-fluorobenzyl   389.47       576   4-fluorobenzyl   389.47       577   indol-3-ylmethyl   410.51       578   furfur-3-ylmethyl   361.44       579   thiophen-3-ylmethyl   377.51       580   pyridin-3-ylmethyl   372.46       581   2-methylbenzyl   385.50       582   3-chlorobenzyl   405.92       583   3-methylbutyl   351.49       584   3-methoxybenzyl   401.50       585   4-trifluoromethoxybenzyl   455.47       586   pyridin-4-ylmethyl   372.46       587   2,4-dichlorobenzyl   440.37       588   pyridine-2-ylmethyl   372.46       589   6-methyl-pyridin-2-ylmethyl   386.49       590   4-bromobenzyl   450.37       591   1-methylpyrrol-2-ylmethyl   374.48       592   2,4-difluorobenzyl   407.46       593   4-carbomethoxybenzyl   429.51       594   cyclohexylmethyl   377.52       595   4-phenylbenzyl   447.57       596   4-thiomethylbenzyl   417.57       597   4-ethylbenzyl   399.53       598   quinolin-2-ylmethyl   422.52       599   4-n-propyloxybenzyl   429.56       600   (S)-(−)-3,7-dimethyloct-6-enyl   419.61       601   3,4-dichlorobenzyl   440.37       602   2,4-dimethylbenzyl   399.53       603   1,4-benzodioxan-6-ylmethyl   429.51       604   3,5-difluorobenzyl   407.46       605   3,4-difluorobenzyl   407.46       606   2-chloro-4-hydroxybenzyl   421.92       607   2-fluoro-3-trifluoromethylbenzyl   457.47       608   3-trifluoromethoxybenzyl   455.47       609   3-bromo-4-methoxybenzyl   480.40       610   3-methylbenzyl   385.50       611   3-bromobenzyl   450.37       612   3,5-dimethoxybenzyl   431.53       613   2-chloro-4-fluorobenzyl   423.91       614   5-chloro-thiophen-2-ylmethyl   411.95       615   2-bromobenzyl   450.37       616   benzofuran-2-ylmethyl   411.50       617   5-bromo-furan-2-ylmethyl   440.33       618   4-diethylaminobenzyl   442.60       619   6-chloro-3,4-methylenedioxybenzyl   449.93       620   3-bromo-4-fluorobenzyl   468.37       621   3-chloro-4-fluorobenzyl   423.91       622   3,5-dichlorobenzyl   440.37       623   4-n-hexyloxybenzyl   471.64       624   trans-4-stilbene-2-yl-methyl   473.61       625   (R)-(+)-3,7-dimethyloct-6-enyl   419.61       626   2-carboethoxy-cycloprop-1-ylmethyl   407.51       627   2,3-dihydrobenzo[b]furan-5-ylmethyl   413.51       628   5-bromothiophen-2-ylmethyl   456.40       629   3-(3,4-dichlorophenoxy)benzyl   432.46       630   3-nitrobenzyl   458.54       631   3,4,5-trihydroxy-n-pentyl   399.49       632   3-cyanobenzyl   396.49       633   4(5)-imidazolylmethyl   361.44       634   3-hydroxybenzyl   387.48                  
 
     EXAMPLE 635  
     1-(2-aminoethyl)-7-propyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-propyl-6-hydrazino-1-isoquinolinone (prepared from n-propyl bromide according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan according to the process outlined in Example 4. After refluxing for four hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH, 5% NH 4 OH in CH 2 Cl 2 ) to afford a light brown oil. Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt as an off white colored solid (MW=305.13; HPLC single component; 1H-NMR, 0.9 6 δ, t, 3H; 3.9 δ, 2H, m).  
      Elemental Analysis for: C 16 H 19 N 3 O 1.0 HCl Calculated; C, 62.84; H, 6.59; N, 13.74 Found: C, 62.96; H, 6.66; N, 13.82  
     EXAMPLES 636-720  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-propyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table IX were obtained and identified by HPLC and mass spectral analyses.  
               TABLE IX                                                                                      Ex.               No.   R4   Mass               636   naphth-2-ylmethyl   409.53       637   4-phenoxybenzyl   451.56       638   ethyl   297.40       639   2-chlorobenzyl   393.91       640   furfur-2-ylmethyl   349.43       641   4-dimethylaminobenzyl   402.53       642   benzyl   359.47       643   thiophen-2-ylmethyl   365.49       644   4-methylbenzyl   373.49       645   4-chlorobenzyl   393.91       646   4-cyanobenzyl   384.48       647   n-pentyl   339.48       648   3,4-methylenedioxybenzyl   403.48       649   4-isopropylbenzyl   401.55       650   5-methylfurfur-2-ylmethyl   363.45       651   4-hydroxybenzyl   375.47       652   4-methoxybenzyl   389.49       653   2-methoxybenzyl   389.49       654   3-fluoro-4-methoxybenzyl   407.48       655   3,5-bis(trifluoromethyl)benzyl   495.46       656   2,6-difluorobenzyl   395.42       657   2-fluorobenzyl   377.46       658   2-trifluoromethylbenzyl   427.46       659   3-trifluoromethylbenzyl   427.46       660   4-trifluoromethylbenzyl   427.46       661   3-fluorobenzyl   377.46       662   4-fluorobenzyl   377.46       663   indol-3-ylmethyl   398.50       664   furfur-3-ylmethyl   349.43       665   thiophen-3-ylmethyl   365.49       666   pyridin-3-ylmethyl   360.45       667   2-methylbenzyl   373.49       668   3-chlorobenzyl   393.91       669   3-methylbutyl   339.48       670   3-methoxybenzyl   389.49       671   4-trifluoromethoxybenzyl   443.46       672   pyridin-4-ylmethyl   360.45       673   2,4-dichlorobenzyl   428.36       674   pyridin-2-ylmethyl   360.45       675   6-methyl-pyridin-2-ylmethyl   374.48       676   4-bromobenzyl   438.36       677   1-methylpyrrol-2-ylmethyl   362.47       678   2,4-difluorobenzyl   395.45       679   4-carbomethoxybenzyl   417.50       680   cyclohexylmethyl   365.51       681   4-phenylbenzyl   435.56       682   4-thiomethylbenzyl   405.56       683   4-ethylbenzyl   387.52       684   quinolin-2-ylmethyl   410.51       685   4-n-propyloxybenzyl   417.55       686   (S)-(−)-3,7-dimethyloct-6-enyl   407.59       687   3,4-dichlorobenzyl   428.36       688   2,4-dimethylbenzyl   387.52       689   1,4-benzodioxan-6-ylmethyl   417.50       690   3,5-difluorobenzyl   395.45       691   3,4-difluorobenzyl   395.45       692   2-chloro-4-hydroxybenzyl   409.91       693   2-fluoro-3-trifluoromethylbenzyl   445.45       694   3-trifluoromethoxybenzyl   443.46       695   3-bromo-4-methoxybenzyl   468.39       696   3-methylbenzyl   373.49       697   3-bromobenzyl   438.36       698   3,5-dimethoxybenzyl   419.52       699   2-chloro-4-fluorobenzyl   411.90       700   5-chloro-thiophen-2-ylmethyl   499.94       701   2-bromobenzyl   438.36       702   benzofuran-2-ylmethyl   399.49       703   5-bromo-furan-2-ylmethyl   428.32       704   4-diethylaminobenzyl   430.59       705   6-chloro-3,4-methylenedioxybenzyl   437.92       706   3-bromo-4-fluorobenzyl   456.35       707   3-chloro-4-fluorobenzyl   411.90       708   3,5-dichlorobenzyl   428.36       709   4-n-hexyloxybenzyl   459.63       710   trans-4-stilbene-2-yl-methyl   461.60       711   (R)-(+)-3,7-dimethyloct-6-enyl   407.59       712   2-carboethoxy-cycloprop-1-ylmethyl   395.50       713   2,3-dihydrobenzo[b]furan-5-ylmethyl   401.50       714   5-bromothiophen-2-ylmethyl   444.39       715   3-(3,4-dichlorophenoxy)benzyl   520.45       716   3-nitrobenzyl   404.46       717   3,4,5-trihydroxy-n-pentyl   387.47       718   3-cyanobenzyl   384.48       719   4(5)-imidazolylmethyl   349.43       720   3-hydroxybenzyl   375.47                  
 
     EXAMPLE 721  
     1-(2-aminoethyl)-7-(pyridin-4-ylmethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-(pyridin-4-ylmethyl)-6-hydrazino-1-isoquinolinone (prepared from 4-bromomethylpyridine according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan according to the process outlined in Example 4. After refluxing for four hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH, 5% NH 4 OH in CH 2 Cl 2 ) to afford a light brown oil. Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt as an off white colored solid (MW=354.83; HPLC single component; 1H-NMR, 5.5 δ, 2H, s).  
      elemental Analysis for: C 19 H 18 N 4 O 1.0 HCl Calculated; C, 64.31; H, 5.40; N, 15.79 Found: C, 64.47; H, 5.47; N, 15.86  
     EXAMPLES 722-806  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-(pyridin-4-ylmethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table X were obtained and identified by HPLC and mass spectral analyses.  
               TABLE X                                                                                      Ex.               No.   R4   Mass               722   naphth-2-ylmethyl   458.56       723   4-phenoxybenzyl   500.60       724   ethyl   346.43       725   2-chlorobenzyl   442.94       726   furfur-2-ylmethyl   398.46       727   4-dimethylaminobenzyl   451.57       728   benzyl   408.50       729   thiophen-2-ylmethyl   414.53       730   4-methylbenzyl   422.52       731   4-chlorobenzyl   442.94       732   4-cyanobenzyl   433.51       733   n-pentyl   388.51       734   3,4-methylenedioxybenzyl   452.51       735   4-isopropylbenzyl   450.58       736   5-methylfurfur-2-ylmethyl   512.49       737   4-hydroxybenzyl   424.50       738   4-methoxybenzyl   438.52       739   2-methoxybenzyl   438.52       740   3-fluoro-4-methoxybenzyl   456.51       741   3,5-bis(trifluoromethyl)benzyl   544.49       742   2,6-difluorobenzyl   444.48       743   2-fluorobenzyl   426.49       744   2-trifluoromethylbenzyl   476.50       745   3-trifluoromethylbenzyl   476.50       746   4-trifluoromethylbenzyl   476.50       747   3-fluorobenzyl   426.49       748   4-fluorobenzyl   426.49       749   indol-3-ylmethyl   447.53       750   furfur-3-ylmethyl   398.46       751   thiophen-3-ylmethyl   414.53       752   pyridin-3-ylmethyl   409.49       753   2-methylbenzyl   422.52       754   3-chlorobenzyl   442.94       755   3-methylbutyl   388.51       756   3-methoxybenzyl   438.52       757   4-trifluoromethoxybenzyl   492.50       758   pyridin-4-ylmethyl   409.49       759   2,4-dichlorobenzyl   477.39       760   pyridin-2-ylmethyl   409.49       761   6-methyl-pyridin-2-ylmethyl   423.51       762   4-bromobenzyl   487.39       763   1-methylpyrrol-2-ylmethyl   411.50       764   2,4-difluorobenzyl   444.48       765   4-carbomethoxybenzyl   466.53       766   cyclohexylmethyl   414.55       767   4-phenylbenzyl   484.60       768   4-thiomethylbenzyl   454.59       769   4-ethylbenzyl   436.55       770   quinolin-2-ylmethyl   459.55       771   4-n-propyloxybenzyl   466.58       772   (S)-(−)-3,7-dimethyloct-6-enyl   456.63       773   3,4-dichlorobenzyl   477.39       774   2,4-dimethylbenzyl   436.55       775   1,4-benzodioxan-6-ylmethyl   466.53       776   3,5-difluorobenzyl   444.48       777   3,4-difluorobenzyl   444.48       778   2-chloro-4-hydroxybenzyl   458.94       779   2-fluoro-3-trifluoromethylbenzyl   494.49       780   3-trifluoromethoxybenzyl   492.50       781   3-bromo-4-methoxybenzyl   517.42       782   3-methylbenzyl   422.52       783   3-bromobenzyl   487.39       784   3,5-dimethoxybenzyl   468.55       785   2-chloro-4-fluorobenzyl   460.93       786   5-chloro-thiophen-2-ylmethyl   448.97       787   2-bromobenzyl   487.39       788   benzofuran-2-ylmethyl   448.52       789   5-bromo-furan-2-ylmethyl   477.36       790   4-diethylaminobenzyl   479.62       791   6-chloro-3,4-methylenedioxybenzyl   486.95       792   3-bromo-4-fluorobenzyl   505.38       793   3-chloro-4-fluorobenzyl   460.93       794   3,5-dichlorobenzyl   477.39       795   4-n-hexyloxybenzyl   508.66       796   trans-4-stilbene-2-yl-methyl   510.63       797   (R)-(+)-3,7-dimethyloct-6-enyl   456.63       798   2-carboethoxy-cycloprop-1-ylmethyl   444.53       799   2,3-dihydrobenzo[b]furan-5-ylmethyl   450.54       800   5-bromothiophen-2-ylmethyl   493.42       801   3-(3,4-dichlorophenoxy)benzyl   569.48       802   3-nitrobenzyl   453.50       803   3,4,5-trihydroxy-n-pentyl   436.51       804   3-cyanobenzyl   433.51       805   4(5)-imidazolylmethyl   398.46       806   3-hydroxybenzyl   424.50                  
 
     EXAMPLE 807  
     1-(2-aminoethyl)-7-(pyridin-2-ylmethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-(pyridin-2-ylmethyl)-6-hydrazino-1-isoquinolinone (prepared from 2-bromomethylpyridine according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan according to the process outlined in Example 4. After refluxing for four hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH, 5% NH 4 OH in CH 2 Cl 2 ) to afford a light brown oil. Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt as an off white colored solid (MW=354.83; HPLC single component; 1H-NMR, 5.5 δ, 2H, s).  
      Elemental Analysis for: C 19 H 81 N 4 O 1.0 HCl Calculated: C, 64.31; H, 5.40; N, 15.79 Found: C, 64.41; H, 5.44; N, 15.80  
     EXAMPLES 808-892  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-(pyridin-2-ylmethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table XI were obtained and identified by HPLC and mass spectral analyses.  
               TABLE XI                                                                                      Ex.               No.   R4   Mass               808   naphth-2-ylmethyl   458.56       809   4-phenoxybenzyl   500.60       810   ethyl   346.43       811   2-chlorobenzyl   442.94       812   furfur-2-ylmethyl   398.46       813   4-dimethylaminobenzyl   451.57       814   benzyl   408.50       815   thiophen-2-ylmethyl   414.53       816   4-methylbenzyl   422.52       817   4-chlorobenzyl   442.94       818   4-cyanobenzyl   433.51       819   n-pentyl   388.51       820   3,4-methylenedioxybenzyl   452.51       821   4-isopropylbenzyl   450.58       822   5-methylfurfur-2-ylmethyl   512.49       823   4-hydroxybenzyl   424.50       824   4-methoxybenzyl   438.52       825   2-methoxybenzyl   438.52       826   3-fluoro-4-methoxybenzyl   456.51       827   3,5-bis(trifluoromethyl)benzyl   544.49       828   2,6-difluorobenzyl   444.48       829   2-fluorobenzyl   426.49       830   2-trifluoromethylbenzyl   476.50       831   3-trifluoromethylbenzyl   476.50       832   4-trifluoromethylbenzyl   476.50       833   3-fluorobenzyl   426.49       834   4-fluorobenzyl   426.49       835   indol-3-ylmethyl   447.53       836   furfur-3-ylmethyl   398.46       837   thiophen-3-ylmethyl   414.53       838   pyridin-3-ylmethyl   409.49       839   2-methylbenzyl   422.52       840   3-chlorobenzyl   442.94       841   3-methylbutyl   388.51       842   3-methoxybenzyl   438.52       843   4-trifluoromethoxybenzyl   492.50       844   pyridin-4-ylmethyl   409.49       845   2,4-dichlorobenzyl   477.39       846   pyridin-2-ylmethyl   409.49       847   6-methyl-pyridin-2-ylmethyl   423.51       848   4-bromobenzyl   487.39       849   1-methylpyrrol-2-ylmethyl   411.50       850   2,4-difluorobenzyl   444.48       851   4-carbomethoxybenzyl   466.53       852   cyclohexylmethyl   414.55       853   4-phenylbenzyl   484.60       854   4-thiomethylbenzyl   454.59       855   4-ethylbenzyl   436.55       856   quinolin-2-ylmethyl   459.55       857   4-n-propyloxybenzyl   466.58       858   (S)-(−)-3,7-dimethyloct-6-enyl   456.63       859   3,4-dichlorobenzyl   477.39       860   2,4-dimethylbenzyl   436.55       861   1,4-benzodioxan-6-ylmethyl   466.53       862   3,5-difluorobenzyl   444.48       863   3,4-difluorobenzyl   444.48       864   2-chloro-4-hydroxybenzyl   458.94       865   2-fluoro-3-trifluoromethylbenzyl   494.49       866   3-trifluoromethoxybenzyl   492.50       867   3-bromo-4-methoxybenzyl   517.42       868   3-methylbenzyl   422.52       869   3-bromobenzyl   487.39       870   3,5-dimethoxybenzyl   468.55       871   2-chloro-4-fluorobenzyl   460.93       872   5-chloro-thiophen-2-ylmethyl   448.97       873   2-bromobenzyl   487.39       874   benzofuran-2-ylmethyl   448.52       875   5-bromo-furan-2-ylmethyl   477.36       876   4-diethylaminobenzyl   479.62       877   6-chloro-3,4-methylenedioxybenzyl   486.95       878   3-bromo-4-fluorobenzyl   505.38       879   3-chloro-4-fluorobenzyl   460.93       880   3,5-dichlorobenzyl   477.39       881   4-n-hexyloxybenzyl   508.66       882   trans-4-stilbene-2-yl-methyl   510.63       883   (R)-(+)-3,7-dimethyloct-6-enyl   456.63       884   2-carboethoxy-cycloprop-1-ylmethyl   444.53       885   2,3-dihydrobenzo[b]furan-5-ylmethyl   450.54       886   5-bromothiophen-2-ylmethyl   493.42       887   3-(3,4-dichlorophenoxy)benzyl   569.48       888   3-nitrobenzyl   453.50       889   3,4,5-trihydroxy-n-pentyl   436.51       890   3-cyanobenzyl   433.51       891   4(5)-imidazolylmethyl   398.46       892   3-hydroxybenzyl   424.50                  
 
     EXAMPLE 893  
     1-(2-aminoethyl)-7-(2-dimethylaminoethyl)-3H,7H-Pyrrolo[3,2-]isoquinolin-6-one  
      A solution of 2-N-(2-dimethylaminoethyl)-6-hydrazino-1-isoquinolinone (prepared from 2-bromo-N,N-dimethylamine according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan according to the process outlined in Example 4. After refluxing for four hours the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH, 5% NH 4 OH in CH 2 Cl 2 ) to afford a light brown oil. Treatment with ethanolic HCl gave the required product as an off white colored solid (MW=370.30; HPLC single component; IH-NMR, 4.4 δ, 2H, t; 3.35 δ, 6H, s).  
      Elemental Analysis for: C 17 H 22 N 4 O 2.0 HCl Calculated: C, 54.99; H, 6.52; N, 15.09 Found: C, 55.17; H, 6.67; N, 15.16  
     EXAMPLES 894-978  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-(2-dimethylaminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table XII were obtained and identified by HPLC and mass spectral analyses.  
     EXAMPLE 979  
     1-(2-aminoethyl)-7-(2-methoxybenzyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-(2-methoxybenzyl)-6-hydrazino-1-isoquinolinone (prepared from 2-methoxybenzylchloride according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan according to the process outlined in Example 4. After refluxing for four hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH, 5% NH 4 OH in CH 2 Cl 2 ) to afford a light brown oil. Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt as an off white colored solid (MW=383.87; HPLC single component; 1H-NMR, 3.8 δ, 3H, s; 5.2 δ, 2H, s).  
      elemental Analysis for: C 21 H 21 N 3 O 2  1.0 HCl Calculated; C, 65.71; H, 5.78; N, 10.95 Found; C, 65.71; H, 5.87; N, 11.16  
     EXAMPLES 980-987  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-(2-methoxybenzyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table XIII were obtained and identified by HPLC and mass spectral analyses.  
               TABLE XIII                                                                                      Ex.               No.   R4   Mass               980   3-nitrobenzyl   482.53       981   3,4,5-trihydroxy-n-pentyl   465.54       982   3-chlorobenzyl   471.98       983   3-methoxybenzyl   467.56       984   pyridin-4-ylmethyl   438.52       985   3-cyanobenzyl   462.55       986   4(5)-imidazolylmethyl   427.50       987   3-hydroxybenzyl   453.54                  
 
     EXAMPLE 988  
     1-(2-aminoethyl)-7-(4-methoxybenzyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 2-N-(4-methoxybenzyl)-6-hydrazino-1-isoquinolinone (prepared from 4-methoxybenzylchloride according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan according to the process outlined in Example 4. After refluxing for four hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH, 5% NH 4 OH in CH 2 Cl 2 ) to afford a light brown oil. Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt as an off white colored solid (MW=383.87; HPLC single component; 1H-NMR, 3.7 δ, 3H, s; 5.2 δ, 2H, s).  
      Elemental Analysis for: C 21 H 21 N 3 O 2 1.0 HCl Calculated: C, 65.71; H, 5.78; N, 10.95 Found: C, 65.79; H, 5.86; N, 11.05  
     EXAMPLES 989-996  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-(4-methoxybenzyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table XIV were obtained and identified by HPLC and mass spectral analyses.  
               TABLE XIV                                                                                      Ex.               No.   R4   Mass               989   3-nitrobenzyl   482.53       990   3,4,5-trihydroxy-n-pentyl   465.54       991   3-chlorobenzyl   471.98       992   3-methoxybenzyl   467.56       993   pyridin-4-ylmethyl   438.52       994   3-cyanobenzyl   462.55       995   4(5)-imidazolylmethyl   427.50       996   3-hydroxybenzyl   453.54                  
 
     EXAMPLE 997  
     1-(2-aminoethyl)-7-(furanyl-2-ylmethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one [furanyl-2-yl or furan-2-yl?] 
      A solution of 2-N-(furanyl-2-ylmethyl)-6-hydrazino-1-isoquinolinone (prepared from furfuryl bromide according to Example 92 and Example 93) was reacted in a Fisher indole reaction with 2-(3-chloropropyl)-1,3-dioxolan according to the process outlined in Example 4. After refluxing for four hours, the product was isolated as reported above and purified by flash silica gel chromatography (20% MeOH, 5% NH 4 OH in CH 2 Cl 2 ) to afford a light brown oil. Treatment with ethanolic HCl gave the required product as its mono hydrochloride salt as an off white colored solid (MW=343.81; HPLC single component; 1H-NMR, 6.3 δ, 2H, s; 5.2 δ, 2H. s).  
      Elemental Analysis for: C 18 H 18 C1N 3 O 2  1.0 HCl Calculated: C, 62.88; H, 5.28; N, 12.22 Found: C, 62.89; H, 5.36; N, 12.35  
     EXAMPLES 998-1005  
      Using essentially the same procedure described in Example 7B and employing 1-(2-aminoethyl)-7-(furan-2-ylmethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one as substrate and a suitable aldehyde, the compounds shown in Table XV were obtained and identified by HPLC and mass spectral analyses.  
               TABLE XV                                                                                      Ex.               No.   R4   Mass                                 998   3-nitrobenzyl   442.47       999   3,4,5-trihydroxy-n-pentyl   425.48       1000   3-chlorobenzyl   431.92       1001   3-methoxybenzyl   427.50       1002   pyridin-4-ylmethyl   398.46       1003   3-cyanobenzyl   422.48       1004   4(5)-imidazolylmethyl   387.44       1005   3-hydroxybenzyl   413.47                  
 
     EXAMPLES 1006-1017  
     1-(2-benzylaminoethyl)-substituted-pyrrolo[3,2-f]isoquinolin-6-one Compounds  
     
       
         
         
             
             
         
       
     
      Using the essentially the same procedure described in Example 7B and employing the appropriate 1-(2-aminoethyl)-pyrrolo[3,2-f]isoquinolin-6-one substrate and benzaldehyde, the compounds shown in Table XVI were prepared and identified by HPLC and mass spectral analyses.  
               TABLE XVI                                                                                                      Ex.                               No.   n   R   R1   R7   R8   Mass               1006   2   H   Br   H   H   432.74       1007   2   CH 3     H   benzyl   H   457.99       1008   2   H   H   phenethyl   H   457.99       1009   2   H   H   naphth-2-ylmethyl   H   508.05       1010   2   H   H   heptyl   H   452.03       1011   2   H   H   3,4-dichlorobenzyl   H   512.86       1012   2   H   H   thiophen-3-yl   H   450.00       1013   3   H   H   H   H   367.87       1014   2   H   4-Cl—C 6 H 5     H   H   478.41       1015   2   H   H   H   Cl   388.29       1016   2   H   H   tetrahydropyran-2-   H   451.99                       ylmethyl       1017   2   H   H   2-methoxyethyl   H   411.92                  
 
     EXAMPLE 1018  
     3,7-dibenzyl-1-(2-dibenzylaminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      Tetrabutylammonium bromide (0.03 g) and benzyl bromide (0.3 g, 1.6 mmol) were added to a solution of the amine from Example 4 (0.1 g, 0.44 mmol) in toluene (2 mL) and 50% aqueous sodium hydroxide (1.8 mmol, 4 equivalents). The mixture was stirred for three hours at room temperature, and the product was purified by flash silica gel chromatography (1% methanolic ammonia in CH 2 Cl 2 ) to afford a brown colored solid. Treatment with ethanolic HCl afforded the salt of the titled compound as an off white colored solid (mp 234-236° C.; MW=624.21; HPLC single component).  
      Elemental Analysis for: C 41 H 37 N 3 O 1.0 HCl Calculated: C, 78.89; H, 6.14; N, 6.73 Found: C, 78.91; H, 6.23; N, 6.84  
     EXAMPLE 1019  
     1-(2-dibenzylaminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      Benzyl bromide (0.226 g, 1.32 mmol) was added to a solution of the amine from Example 4 (0.2 g, 0.88 mmol) in DMF (2 mL) and 50% aqueous sodium hydroxide (1.75 mmol, 2 equivalents). The mixture was stirred for two hours at room temperature, and the product was purified by flash silica gel chromatography (4% methanolic ammonia in CH 2 Cl 2 ). Treatment with ethanolic HCl afforded the salt of the titled compound as a white solid (mp 250-253° C.; MW=624.21; HPLC single component).  
      Elemental Analysis for: C 27 H 25 N 3 O 1.0 HCl Calculated: C, 73.04; H, 5.90; N, 9.46 Found: C, 73.20; H, 5.99; N, 9.56  
     EXAMPLE 1020  
     1-[2-(benzyl-methylamino)ethyl]-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      A solution of 6-hydrazino-1-isoquinolinone (0.4 g, 1.89 mmol) from Example 3 and 2-(3-(N-methyl-benzylamine)propyl)-1,3-dioxolan (0.668 g, 2.84 mmol) in degassed ethanol (120 ml)/4% aqueous sulfuric acid (12 ml) was refluxed under nitrogen for six hours. The reaction mixture was concentrated in vacuo and the product purified by flash silica gel chromatography to afford an orange colored solid (0.155 g, 25% yield). Treatment of the product with ethereal [v. ethanolic?] HCl and crystallization from ethanol ether gave the mono hydrochloride salt as a light amber colored solid (mp=152-155° C.; MW=367.87; HPLC single component).  
      Elemental Analysis for: C 21 H 21 N 3 O 1.0 HCl Calculated: C, 68.56; H, 6.03; N, 11.42 Found: C, 88.62; H, 6.12; N, 11.54  
     EXAMPLE 1021  
     1-(2-methylaminoethyl)-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one  
      1-[2-(Benzylmethylamino)ethyl]-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one (1.07 g, 3.22 mmol) from Example 1020 was hydrogenated over 10% Pd/C at 50 psi H 2  for 24 hours. The catalyst was removed by filtration, and the product was converted to its HCl salt by the action of ethanolic HCl. Recrystallization from EtOH/Et 2 O afforded the titled compound as a light brown colored solid (mp=160° C.; MW=377.75; HPLC single component).  
      Elemental Analysis for: C 14 H 15 N 3 O 1.0 HCl Calculated: C, 60.54; H, 5.81; N, 15.13 Found: C, 60.64; H, 5.98; N, 15.24  
     EXAMPLE 1022  
     N-[2-(7-benzyl-6-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]isoquinolin-1-yl)-ethyl]-benzenesulfonamide  
      A solution of 1-(2-aminoethyl)-7-benzyl-3H,7H-pyrrolo[3,2-f]isoquinolin-6-one (0.25 g, 0.788 mmol) from Example 182 in DMF (4 mL) was treated with sodium hydride (1.2 equivalents) at 0° C. followed after 15 minutes with the addition of benzene sulfonylchloride (0.18 g, 1.02 mmol, 1.3 equivalents). The mixture was stirred for 16 hours and the titled compound isolated as a white solid (m.p. 205-206° C.; MW=457.55; HPLC single component) by flash silica gel chromatography (5% MeOH in CH 2 Cl 2 ).  
      Elemental Analysis for: C 26 H 23 N 3 O 3 S Calculated: C, 68.25; H, 5.07; N, 9.18 Found: C, 68.33; H, 5.18; N, 9.27  
     EXAMPLE 1023  
     7-fluoro-3H-quinazolin-4-one  
      A solution of 2-amino-4-fluorobenzoic acid (8.8 g, 56.7 mmol) and formamidine acetate (23.63 g, 227 mmol, 4 equivalents) in ethoxyethanol (400 ml) was refluxed for 16 hours. The solvent was removed in vacuo and the residue crystallized from methanol-water to provide the titled compound as a light brown solid (8.35 g, 90% yield, M+1=165).  
      Elemental Analysis for: C 8 H 5 FN 2 O Calculated: C, 58.54; H, 3.07; N, 17.07 Found: C, 58.60; H, 3.19; N, 17.27  
     EXAMPLE 1024  
     7-fluoro-3-methyl-3H-quinazolin-4-one  
      Sodium hydride (19.0 mmol, 1.2 eq) was added to a solution of 7-fluoro-3H-quinazolin-4-one (2.6 g, 15.8 mmol, Example 1023) in DMF (30 ml) under an atmosphere of nitrogen at −20° C. After stirring for one hour, methyl iodide (19.8 mmol, 1.25 equivalents) was added, and the resulting solution was stirred at room temperature for two hours. Water (100 ml) was added and the product extracted into CH 2 Cl 2  (3×100 ml). The organics were concentrated in vacuo and the product crystallized from hexane/CH 2 Cl 2  to afford the titled compound as a light amber colored solid (m.p. 133-135° C., M+1=179).  
      Elemental Analysis for: C 9 H 7 FN 2 O Calculated: C, 60.67; H, 3.96; N, 15.72 Found: C, 60.72; H, 3.99; N, 15.79  
     EXAMPLE 1025  
     7-hydrazino-3-methyl-3H-quinazolin-4-one  
      A solution containing 7-fluoro-3-methyl-3H-quinazolin-4-one (2.2 g, 12.3 mmol, Example 1026) and hydrazine (7.88 g, 20 equivalents) in dioxane (50 ml) was refluxed for 16 hours under an atmosphere of nitrogen. The mixture was concentrated in vacuo, triturated with dioxane and the resulting solid washed with water (50 ml) and dried under vacuum to provide the titled compound as a white solid (1.63 g, 70% yield, m.p. 208-211° C., M+1=191).  
      Elemental Analysis for: C 9 H 10 N 4 O Calculated: C, 56.83; H, 5.30; N, 29.46 Found: C, 56.98; H, 5.39; N, 29.59  
     EXAMPLE 1026  
     3-benzyl-7-fluoro-3H-quinazolin-4-one  
      Sodium hydride (22.0 mmol, 1.2 equivalents) was added to a solution of 7-fluoro-3H-quinazolin-4-one (3.0 g, 18.3 mmol, Example 1023) in DMF (40 ml) under an atmosphere of nitrogen at −20° C. After stirring for one hour, benzyl bromide (3.7 g, 22 mmol, 1.2 equivalents) was added, and the resulting solution was stirred at room temperature for two hours. Water (100 ml) was added and the product extracted into CH 2 Cl 2  (3×100 ml). The organics were concentrated in vacuo and the product crystallized from hexane/CH 2 Cl 2  to afford the titled compound as a light brown/beige colored solid (m.p. 110-111° C., M+1=255).  
      Elemental Analysis for: C 9 H 7 FN 2 O Calculated: C, 70.86; H, 4.36; N, 11.02 Found: C, 70.94; H, 4.39; N, 11.19  
     EXAMPLE 1027  
     3-benzyl-7-hydrazino-3H-quinazolin4-one  
      A solution containing 3-benzyl-7-fluoro-3H-quinazolin-4-one (3.0 g, 11.8 mmol) and hydrazine (7.56 g, 20 equivalents) in dioxane (60 ml) was refluxed for 16 hours under an atmosphere of nitrogen. The mixture was concentrated in vacuo, and the resulting solid crystallized from methanol/water to provide the titled compound as a cream colored solid (2.4 g, 76% yield, m.p. 165-169° C., M+1=267).  
      Elemental Analysis for: C 15 H 14 N 4 O Calculated: C, 67.65; H, 5.30; N, 21.04 Found: C, 67.78; H, 5.41; N, 21.19  
     EXAMPLE 1028  
     9-(2-aminoethyl)-3-methyl-3H,7H-pyrrolo[2,3-h]quinazolin-4-one  
      A solution of 7-hydrazino-3-methyl-3H-quinazolin-4-one (1.48 g, 7.78 mmol), sulfuric acid (1N, 16 ml) and 2-(3-chloropropyl)-1,3-dioxolan (1.41 g, 9.34 mmol) in degassed ethanol (50 ml)/water (50 ml) was refluxed under nitrogen for three hours. The reaction mixture was concentrated in vacuo and the product purified by flash silica gel chromatography, eluting with Et 3 N (2%): MeOH (20%): CH 2 Cl 2  (78%), affording an amber colored solid (1.245 g). The product was crystallized from ethanol to afford the titled compound as a light amber colored solid (m.p. 279-285° C., M+1=243).  
      Elemental Analysis for: C 13 H 14 N 4 O Calculated: C, 64.45; H, 5.82; N, 23.12 Found: C, 64.58; H, 5.89; N, 23.19  
     EXAMPLES 1029-1032  
     9-(2-Aminoethyl)-substituted-pyrrolo[2,3-h]quinazolin-4-one Compounds  
     
       
         
         
             
             
         
       
     
      Using the essentially the same procedure described in Example 1028 and employing the appropriate 7-hydrazino-3H-quinazolin-4-one substrate and 2-(3-chloropropyl)-1,3-dioxolan, the compounds shown in Table XVII were prepared and identified by HPLC and mass spectral analyses.  
               TABLE XVII                                                                                              Ex.           mp           No.   R6   R7   ° C.   [M + H]               1029   H   benzyl   302-305   319       1030   CH 3     CH 3     —   —       1031   3-pyridinyl   H   —   —       1032   H   H   —   —                  
 
     EXAMPLE 1033  
       
      Comparative Evaluation of 5-HT 6  Binding Affinity of Test Compounds  
      The affinity of test compounds for the 5-HT 6  receptor is evaluated in the following manner. Cultured Hela cells expressing human cloned 5-HT 6  receptors are harvested and centrifuged at low speed (1,000×g) for 10.0 min to remove the culture media. The harvested cells are suspended in half volume of fresh physiological phosphate buffered saline (PBS) solution and recentrifuged at the same speed. This operation is repeated. The collected cells are then homogenized in ten volumes of 50 mM Tris.HCl (pH 7.4) and 0.5 mM EDTA. The homogenate is centrifuged at 40,000×g for 30.0 min, and the precipitate is collected. The obtained pellet is resuspended in 10 volumes of Tris.HCl buffer and recentrifuged at the same speed. The final pellet is suspended in a small volume of Tris.HCl buffer, and the tissue protein content is determined in aliquots of 10-25 microliter volumes. Bovine Serum Albumin is used as the standard in the protein determination according to the method described in Lowry et al.,  J. Biol. Chem.  1951, 193, 265. The volume of the suspended cell membranes is adjusted to give a tissue protein concentration of 1.0 mg/ml of suspension. The prepared membrane suspension (10 times concentrated) is aliquoted in 1.0 ml volumes and stored at −70° C. until used in subsequent binding experiments.  
      Binding experiments are performed in a 96-well microtiter plate format, in a total volume of 200 microliters. To each well is added the following mixture: 80.0 microliter of incubation buffer made in 50 mM Tris.HCl buffer (pH 7.4) containing 10.0 mM MgCl 2  and 0.5 mM EDTA and 20 microliters of [ 3 H]-LSD (S.A., 86.0 Ci/mmol, available from Amersham Life Science), 3.0 nM. The dissociation constant, K D  of the [ 3 H]-LSD at the human 5-HT 6  receptor is 2.9 nM, as determined by saturation binding with increasing concentrations of [ 3 H]-LSD. The reaction is initiated by the final addition of 100.0 microliters of tissue suspension. Nonspecific binding is measured in the presence of 10.0 micromoles methiothepin. The test compounds are added in 20.0 microliter volume.  
      The reaction is allowed to proceed in the dark for 120 min at room temperature, at which time, the bound ligand-receptor complex is filtered off on a 96-well unifilter with a Packard Filtermate® 196 Harvester. The bound complex caught on the filter disk is allowed to air dry, and the radioactivity is measured in a Packard TopCount® equipped with six photomultiplier detectors, after the addition of 40.0 micoliters Micorscint®-20 scintillant to each shallow well. The unifilter plate is heat-sealed and counted in a Packard TopCount® with a tritium efficiency of 31%.  
      Specific binding to eh 5-HT 6  receptor is defined as the total radioactivity bound less the amount bound in the presence of 10.0 microliter unlabelled methiothipin. Binding in the presence of varying concentrations of test compound is expressed as a percentage of specific binding in the absence of test compound. The results are plotted as log % bound versus log concentration of the test compound. Nonlinear regression analysis of data points with a computer assisted program Prism® yielded both the IC 50  and the K i  values of the test compounds with 95% confidence limits. A linear regression is plotted, from which the IC 50  value is determined, and the K i  value is determined based upon the following equation: 
 
 K   i =IC 50 /(1 +L/K   D ) 
 
 where L is the concentration of the radioactive ligand used and K D  is the dissociation constant of the ligand for the receptor, both expressed in nM. 
 
      Using this assay, the K i  values were determined and are shown in Table XVIII below.  
                           TABLE XVIII                                      Test Compound   5-HT6 binding Ki           (Ex. No.)   (nM)                         7   15            94   18            182   11            269   13            274   11           1021   21           1029   32.0                       Comparative   5-HT6 Binding Ki           Examples   (nM)                       loxapine   41.4           bromocriptine   23.0           methiothepin   8.3           mianserin   44.2           olanzepine   19.5