JPH09505600A - Therapeutic guanidines - Google Patents

Abstract

(57) Summary The present invention provides N, N'-diaryl substituted guanidines having therapeutic applications. The compounds of the present invention are of formula (I), wherein R and R ¹ represent hydrogen or other groups, Ar and Ar ¹ represent selected aryl groups, at least one of which is acenaphthyl. .

Description

Detailed Description of the Invention                           Therapeutic guanidinesBackground of the Invention 1.Field of the invention   The present invention is directed to certain substituted guanidines, as well as one or more such guanidines. Treatment methods using the above, and pharmaceutical compositions containing one or more such guanidines About. 2.background   Mature central nervous system (“CNS”) neurons are highly specific and generally It does not succeed itself. Therefore, death or degeneration of cells in the nervous system Can have far more serious consequences than cell death or degeneration in an organ . Abnormal death of neurons is rapid and widespread, as in traumatic brain injury. Sometimes, and as in the case of chronic neurodegenerative disorders, it is very specific. It can occur over many years in the Ron population.   Significant evidence now contributes in many cases of pathological neuronal degeneration As a mechanism, he points out malignant hyperfunction of the normal neurotransmission system. Especially the brain L-glutamine, the most predominant excitatory amino acid (“EAA”) neurotransmitter Stimulation of acid neuronal receptors is triggered in some acute neuropathy Recognized as a factor or aggravator and is also the root of many chronic neurodegenerative diseases Is proposed. Choi, D. W., Neuron., 1: 623 (1988); Choi, D .; W., Cerebrov . and Brain Metab. Rev., 2: 105 (1990); Albers, G. W. Et al., Ann. Neurol., 25 : 398 (1989). In fact, seen during seizures, hypoxia, hypoglycemia and trauma Acute injuries to the nervous system as well as chronic degenerative diseases such as Han Tinton's disease, glutamate dehydrogenase deficiency and glutamate catabolism Pontine cerebellar atrophy, amyotrophic lateral sclerosis / Parkinsonni associated with reduced use Glutamate neurotoxin in um dementia, Parkinson's disease and Alzheimer's disease It is thought that sex is involved. Choi, D. W., Neuron, 1: 623-634 (1988); Choi , D. W., Cereb. Brain Met., Rev. 2: 105-147 (1990); Courtier et al., Lancet, 34. 1: 265-268 (1993); Appel, S .; H., Trends Neurosci., 16: 3-5 (1993).   In the mammalian brain, glutamate is one of the three major classes or receptors, Ie N-methyl-D-aspartate (“NMDA”) receptors, non-NMD Interacts with A and metabotropic receptors (Watkins, JD, et al. Trends Ne urosci., 10: 265 (1987) and Seeburg, TIPS, 141: 297 (1993)). These three categories All glutamate receptors elicit a unique post-synaptic response, yet Free Ca in transcellular²⁺Can act to increase the intracellular concentration of (AB . MacDermott, Nature 321: 519 (1986)). Thus, glutamate to the NMDA receptor The binding of tamate is Ca²⁺Cation-selective channels that are significantly permeable to water Open the intracellular Ca²⁺Results in a large and rapid increase in. Non-NMDA receptor Are usually bound to cation channels that largely exclude calcium However, by depolarizing the cell membrane, it reverses voltage-activated Ca.²⁺Open channel Ca to neurons²⁺Can be indirectly promoted. On the other hand The loose "metabolism receptor" is not associated with ion channels but Ca from intracellular storage via jasinositol triphosphate²⁺Promotes the release of can do.   Regardless of induction mechanism, cytosolic Ca²⁺Long-term increase in neuron destruction It is considered to be a factor in the beginning of. Intracellular Ca²⁺increase of Adverse effects of mitochondrial respiratory disorders, Ca²⁺Lipa, a dependent protease Enzyme and endonuclease activation, free radical formation and cell membrane lipid peracid There is a change.   NMDA subtypes of excitatory amino acid receptors follow brain or spinal cord ischemia It is strongly involved in nerve cell death that occurs. Ischemic brain injury, eg stroke, heart attack Or when traumatic brain injury occurs, excessive release of endogenous glutamate occurs. Resulting in overstimulation of NMDA receptors. Ion channel for NMDA receptors Le is involved. The recognition site, the NMDA receptor, is the ion channel To the outside. When glutamate interacts with the NMDA receptor, glutamate Cations that open the on-channel, thereby penetrating the cell membrane, such as Ca²⁺ And Na⁺Permitting the influx of⁺Allow outflow from cells. This ion Of Ca2 +, especially Ca produced by the interaction of glutamate with NMDA receptors²⁺ It is believed that the influx of ions plays an important role in neuronal cell death. For example, Rothman, S. M. and Olney, J. M., Trends in Neurosci., 10 (7): 299-302 (19 See 87). In addition, excessive seizures of neurons in epileptic seizures Occurrence and excessive activation of NMDA receptors contribute to the pathophysiology of epilepsy Have been proved (Porter, R.J., Epilepsia, 30 (Suppl. 1): S29-S34 (1989)). And Rogawski, M .; A., et al., Pharmacol. Rev., 42: 224-286 (1990)).   Non-NMDA receptors directly interact with ion channels, as in the case of NMDA receptors. Constitutes a broad category of post-synaptic receptor sites that are physically associated. Specifically The receptor site is a physical part of a particular ion channel protein. Non-N MDA receptors are broadly classified into two groups based on compounds that are selective for them. The major subclass, namely kainate It has been characterized in the receptor and AMPA / quisqualate receptors. J. C. Watkin See S. et al., Trends Neurosci., 10: 265 (1987). AMPA is α-a Abbreviation for mino-3-hydroxyl-5-methyl-isoazolepropionic acid . These subclasses can be classified as "non-NMDA" receptors.   Non-NMDA receptors are less subject to pharmacological scrutiny than NMDA receptors. Not available (existing antagonists are all competitive) and in vivo studies in this area Has been hampered by the lack of drugs that penetrate the blood-brain barrier. Also kawaka And in vivo studies show that non-NMDA receptor agonists require longer exposure. But clearly demonstrated that it can be as excitotoxic as an NMDA agonist did. In addition, evidence from animal and human epidemiological studies has shown that non-NMDA That body-mediated excitotoxicity is clinically important in certain medical conditions Suggests. M. D. See Ginsberg et al., Stroke, 20: 1627 (1989).   One such disorder follows heart attack, drowning and carbon monoxide poisoning. Cerebral ischemia. Transient agitation of cerebral blood supply in laboratory animals Blockade causes a syndrome of selective neuronal necrosis, with no resistance Special populations of neurons (neocortical layers 3, 5 and 6, hippocampal areas CA1 and CA) In cone cells and small and medium striatal neurons in 3) Occur. The time course of this degeneration is also regionally variable, a few hours (striatum). It may range from several days (hippocampus).   NMDA antagonists generally demonstrate high efficacy in animal models of global ischemia I haven't. In fact, the positive results obtained with NMDA antagonists are mainly human. It has been suggested that it may be artificial. In contrast, the competition , 3-Dihydroxy-6-nitro-7-, a potent non-NMDA receptor antagonist Sulfamoyl-benzo (F) quinoxaline (“NBQX”) is a combination of gerbil and Neuronal degeneration following transient forebrain ischemia in both rats and rats Shows dramatic effectiveness in preventing M. J. Sheardown et al., Science, 247: 571-5. 74 (1990).   Currently, there is an effective cure to control the extent of neuronal cell death following stroke or traumatic brain injury. There is an urgent need for medical treatment. In elucidation of the mechanism underlying this nerve cell death Recent advances have led to the hope that drug therapies can be developed. In this field Research and development efforts in mediated by NMDA receptor-channel complexes The focus has been on blocking the action of glutamate. Two methods have been developed I have. Competitive NMDA receptor antagonist (Choi D.W., Cerebrov. Brain Metab., Re v. 1: 165-211 (1990); Watkins, J.C. And Olverman, H.J., Trends Neurosci. , 10: 265-272 (1987)) and ions of the NMDA receptor ion channel complex. Channel blockers (Meldrum, B., Cerebrovascular Brain Metab., Rev. 2: 27- 57 (1987); Choi, D.W., Cerebrovascular Brain Metab., Rev. 2: 105-147 (1987) And Kemp, J.A. et al., Trends Neurosci., 10: 265-272 (1987)). However, Some toxicity of some ion channel blockers such as MK-801 is reported. Was told. (See Merck Index, monograph 3392, 11th ed., 1989). Olney, J. W. Et al., Science, 244: 1360-1362 (1989); Koek, W .; And Colpaert, J., J. Pha rmacol. Exp. Ther., 252: 349-357 (1990). NMDA antagonists also acquire memory Was shown to be inhibited. Morris, R.G.M., in Excitat. A.A.'s in Health a nd Disease, D.D. Lodge (ed.), Wiley, 297-320 (1988).   Blockers of neurotransmitter release become potential neuroprotective agents It's getting a lot of attention. Meldrum, B., Cerebrovascular and Brain Metab., Rev. 2: 27-57 (1990); Dolphin, A.C. Nature, 316: 148-150 (1985)); Evans, M.C. et al. Neurosci. Lett., 83: 287-292 (1987); Ault, B. and Wang, C.M., Br.J. Phar macol., 87: 695-703 (1986); Kaneko, T .; Et al., Arzneim-Forsch./Drug Res., 39: 4. 45-450 (1989); Malgouris, C.I. J. et al. Neurosci., 9: 3720-3727 (1989); Jimonet , P. Et al., Bio Organ. and Med. Chem. Lett., 983-988 (1993); Wahl, F .; Et al, Eu r.J. Pharmacol., 230: 209-214 (1993); Koek, J.W. And Colpaert, F.C., J. Pharmacol. Exp. Ther., 252: 349-357 (1990); Kaneko, T. et al., Arzneim.-Forsch. / Drug Res. 39: 445-450 (1989). Inhibits glutamate release It was reported that certain of the above compounds also exhibit anticonvulsant activity. Malg ouris, C. J. et al. Neurosci., 9: 3720-3727 (1989); Miller et al., New Anticonvuls. ant Drugs, Meldrum, B.S. And Porter R.J. (eds), London: John Libbey, 16 5-177 (1986).   Calcium antagonists like nimodipine also act as cerebral vasodilators (Wong, M.C.W. and Haley, E.C.Jr., Stroke, 24: 31-36 (1989)), It also acts to block calcium entry into neurons (Scriabine, A ., Adv. Neurosurg. (1990)) has been reported. Yes in the outcome of the seizure Some improvement has been observed in clinical trials. Gelmers, H .; J. et al., N. Eng. J. Med ., 318: 208-207 (1988). Nimodipine has significant cardiovascular side effects , Appears to be less toxic than certain NMDA antagonists.   Antagonists of voltage-gated Na channels can be neuroprotective. Grah am, S. H., J. Chen, F. H. Sharp and R.M. P. Simon, J. Cereb. Blood Flow and Metab., 13: 88-97 (1993), Meldrum, B. S. et al. Brain Res., 593: 1-6 and Stys, P. K. , S. G. Waxman and B. R. Ransom , J. et al. Neurosci., 12: 430-439 (1992). In the case of a stroke, the blood supply from the clot Persistent hypoxia develops from the obstruction to the "core area". When hypoxia develops, Depletion of ATP prevents Na and K-ATPase from maintaining an ionic gradient Which causes the normal membrane potential of resting nerve cells to develop. Cell depolarized When the action potential ignition threshold is reached, the Na channel is activated. stys et al (Stys, PK, SG Waxman and BR Ransom, J. Neurosci., 12: 430-439. (1992)) recently expressed Na channel hyperactivity in central white matter anoxia. And Na channel blockers tetrodotoxin (TTX) and Saki The neuroprotective effect of cytoxin (STX) has been demonstrated in vitro.Summary of the invention   The present invention provides N, N'-diaryl substituted guanidines of formula I . (In the formula, R and R¹Are each independently hydrogen, 1 to about 20 carbon atoms. Substituted or unsubstituted alkyl having, also substituted with 2 to about 20 carbon atoms Or unsubstituted alkenyl, substituted or unsubstituted having 2 to about 20 carbon atoms. A substituted alkynyl, a substituted or unsubstituted alkene having from 1 to about 20 carbon atoms Xy, a substituted or unsubstituted aminoalkyl having 1 to about 20 carbon atoms, A substituted or unsubstituted alkylthio having 1 to about 20 carbon atoms, 1 to about 2 A substituted or unsubstituted alkylsulfinyl having 0 carbon atoms, 1 to about 2 A unit having 0 carbon atoms A substituted or unsubstituted alkylsulfonyl, a moiety having at least about 5 ring atoms Substituted or unsubstituted carbocyclic aryl, substituted with at least about 5 ring atoms Or an unsubstituted aralkyl, or 1 to 3 rings with 3 to 8 rings in each ring Substituted or unsubstituted heteroaromatic having a ring member and having 1 to 3 heteroatoms Or a heteroalicyclic group;   Ar is a substituted or unsubstituted carbocyclic alkenyl group having at least 5 carbon atoms. 1 to 3 reels and 1 to 3 rings, 3 to 8 ring members in each ring Selected from the group consisting of substituted or unsubstituted heteroaromatic groups containing heteroatoms Be done) And a pharmaceutically acceptable salt thereof.   Preferred compounds of formula I include those of formula IA. (In the formula, R and R¹Are each independently hydrogen, 1 to about 20 carbon atoms. Substituted or unsubstituted alkyl having, also substituted with 2 to about 20 carbon atoms Or unsubstituted alkenyl, substituted or unsubstituted having 2 to about 20 carbon atoms. A substituted alkynyl, a substituted or unsubstituted alkene having from 1 to about 20 carbon atoms Xy, a substituted or unsubstituted alkylthio having 1 to about 20 carbon atoms, 1 To substituted or unsubstituted aminoalkyl having from about 20 carbon atoms, 1 to about 2 A substituted or unsubstituted alkylsulfinyl having 0 carbon atoms, 1 to about 2 A substituted or unsubstituted alkylsulfonyl having 0 carbon atoms, at least A substituted or unsubstituted carbocyclic aryl having about 5 ring atoms, at least about A substituted or unsubstituted aralkyl having 5 ring atoms, or 1 to 3 rings Have Substituted or non-substituted having 3 to 8 ring members in each ring and having 1 to 3 heteroatoms. A substituted heteroaromatic or heteroalicyclic group;   Ar is a substituted or unsubstituted carbocyclic alkenyl group having at least 5 carbon atoms. 1 to 3 reels and 1 to 3 rings, 3 to 8 ring members in each ring Selected from the group consisting of substituted or unsubstituted heteroaromatic groups containing heteroatoms Be done) And a pharmaceutically acceptable salt thereof.   Another group of preferred compounds of the invention are compounds of formula IB (In the formula, R, R₁And Ar is the same as defined for formula IA). And a pharmaceutically acceptable salt thereof.   In another embodiment, preferred compounds of formula I are N- and / or N ' -Including guanidines having one or more ring substituents having an acenaphthyl substituent No. Particularly preferred compounds have the following formula IIA: (In the formula, R, R¹And Ar are the same as described above for Formula IA,   Each R²Are each independently halogen, hydroxyl, cyano, isocyanate Nitro, amide, azide, substituted or non-substituted having 1 to about 20 carbon atoms Substituted alkyl, substituted if having from 2 to about 20 carbon atoms Or unsubstituted alkenyl, substituted or unsubstituted having 2 to about 20 carbon atoms An alkynyl, a substituted or unsubstituted alkoxy having 1 to about 20 carbon atoms. Ci, substituted or unsubstituted alkylthio having 1 to about 20 carbon atoms, 1 A substituted or unsubstituted aminoalkyl having about 20 carbon atoms, 1 to about 20 A substituted or unsubstituted alkylsulfinyl having 1 carbon atom, 1 to about 20 A substituted or unsubstituted alkylsulfonyl having 1 carbon atom, or less Both are substituted or unsubstituted aralkyl having about 5 ring atoms; n is independently an integer of 1 to 9) And a pharmaceutically acceptable salt thereof.   Also preferred are guanidines having a substituted 3-acenaphthyl group, especially The following formula IIB: (In the formula, R, R¹And Ar are the same as described above for Formula IA,   Each R²Are each independently halogen, hydroxyl, cyano, isocyanate Nitro, amide, azide, substituted or non-substituted having 1 to about 20 carbon atoms Substituted alkyl, substituted or unsubstituted alkene having 2 to about 20 carbon atoms. Nyl, a substituted or unsubstituted alkynyl having 2 to about 20 carbon atoms, 1 A substituted or unsubstituted alkoxy having about 20 carbon atoms, 1 to about 20 Substituted or unsubstituted alkylthio having carbon atoms, 1 to about 20 carbon atoms A substituted or unsubstituted aminoalkyl having 1 to about 20 carbon atoms Replacement or non-replacement Rukylsulfinyl, a substituted or unsubstituted alkyl group having 1 to about 20 carbon atoms. Rucylsulfonyl, or substituted or non-substituted having at least about 5 ring atoms A replacement aralkyl; n is independently an integer of 1 to 9) And a pharmaceutically acceptable salt thereof.   Preferred compounds of formula IIA or IIB are those in which n is 1, 2 or 3 and more preferred Specifically, it includes a compound in which n is 1 or 2. A compound of formula IIA or IIB is Preferably, the position 3, 4, 5, 6, 7 and / or 8 of the acenaphthyl group is 1 R or more²Substituted by a group.   Preferred compounds of formula I, IA, IB, IIA or IIB are disubstituted guanidines. , Ie R and R¹Are each hydrogen, and in particular the groups Ar and / or A r¹Is a heterocyclic group or a substituted or unsubstituted carbocyclic aryl group, for example , Unsubstituted or substituted biphenyl, and mono-substituted phenyl, di-substituted phenyl And unsubstituted or substituted phenyl, including trisubstituted phenyl. As well The new ones are trisubstituted guanidines (ie R and R¹One is hydrogen) And tetrasubstituted guanidines (ie R and R¹Are all other than hydrogen) And in particular the groups Ar and / or Ar¹Is a heterocyclic group or substituted or non- Substituted carbocyclic aryl groups, such as unsubstituted and substituted biphenyls, and Unsubstituted and substituted including mono-substituted phenyl, di-substituted phenyl and tri-substituted phenyl It is a substitute phenyl.   The compounds of the present invention may exist as any of numerous tautomers. . All such tautomers are within the scope of the invention. That is, the formulas I, I A, IB, IIA and IIB include tautomers of the specified guanidines .   Preferred compounds of the invention release neurotransmitters, preferably glutamate. Modulate, especially inhibit. More preferably, the preferred substituted guanidines are ischemic Neurons from neuronal cells, especially mammalian cells such as human neuronal cells Modulates, especially inhibits the release of transmitters (eg glutamate).   Most of the particularly preferred guanidines of the above formula IA, IB, IIA or IIB are As discussed further below, the K-induced glutamate release assay and veratridine. It would be active in a guanine-induced glutamate release assay. These as above Particularly preferred compounds are 3-acenaphthyl or 5 on the first guanidine nitrogen. -Either substituted or unsubstituted on the acenaphthyl group and the second guanidine nitrogen And aryl groups, especially phenyl groups.   The N, N'-diaryl-substituted guanidines of the present invention can be used in certain neurotransmitter cis Stem from the modulation of the system and also either of the same or different class of neurotransmitters Can be interfered with by one or more substituted guanidines of the invention acting on It is useful in many therapeutic applications, including the treatment of possible diseases.   The present invention also relates to epilepsy, neurodegenerative conditions and / or hypoxia, hypoglycemia, brain Or spinal cord ischemia, brain or spinal cord injury, stroke, heart attack, drowning or monoxide For the treatment and / or prevention of neurological conditions such as neuronal cell death resulting from carbon poisoning Method. The compounds of the invention are also useful in Parkinson's disease, Huntington's disease, muscle. Atrophic lateral sclerosis, Alzheimer's disease, Down's syndrome, Korsakoff's disease, olive Species such as pontocerebellar atrophy, HIV-induced dementia and blindness or multiple infarct dementia It is useful for treating and / or preventing various neurodegenerative diseases. Embodiment of the present invention The compound is also Used to treat anxiety by administration to subjects susceptible to systemic anxiety disorder, for example May be. The compounds of the invention are also useful in treating epilepsy. Of the present invention Compounds cause global cerebrum that can follow heart attack, drowning and carbon monoxide poisoning It is particularly useful for treating ischemia. The treatment method (including prophylactic treatment) of the present invention is Generally, a therapeutically effective amount of one or more compounds of Formula I, IA, IB, IIA or IIB , Administration to animals including mammals, particularly humans.   The present invention also provides a pharmaceutical composition comprising one or more compounds of formula I and a suitable carrier. Offer.Detailed description of the invention   The compounds of the invention modulate, ie inhibit or enhance, the release of neurotransmitters Ability, or shortening the elapsed time of neurotransmitter action from neuronal tissue Has been found to preferably have the ability to prolong. Therefore, this compound Treats pathophysiological conditions resulting from excessive or inadequate release of neurotransmitters Have been found to be useful in prevention. The substituted guanidines of the present invention are Blocking nasal calcium and / or sodium channels Mediates inhibition of neurotransmitter release. Therefore, the present invention Cells, especially mammalian cells such as human neuronal cells, A method of blocking um and sodium channels comprising the formulas I, IA, Administering to a cell an effective amount of a compound of IB, IIA or IIB, especially such a Methods of administration to mammals in need of treatment are provided. Of neuronal cells Excessive release of endogenous neurotransmitters by such blockade of calcium channels The symptoms associated with can be treated.   In particular, it may inhibit the release of excitatory amino acids, such as glutamate. And can reduce disorders such as neuronal damage in stroke . Disorders such as depression are associated with the release of inhibitory neurotransmitters such as γ-aminobutyric acid. Can be reduced by inhibiting To be bound by theory Although undesired, administration of a compound of the invention results in excitatory neurotransmitters, such as Inhibiting the release of lutamate releases an inhibitory transmitter such as γ-aminobutyric acid. The onset or subsequent effects can be indirectly enhanced. Therefore, the present invention Compounds are known to be attenuated by more direct enhancement of inhibitory neurotransmission Disorders such as anxiety or insomnia can be treated.   The compound of the present invention was prepared according to the protocol disclosed in Example 64 below to about 10 At a concentration of 0 μM, at least about 50% of a neurotransmitter, eg glutamate Is considered an effective inhibitor of neurotransmitter release if it causes inhibition of You can More preferably, the compound is the compound disclosed in Example 64 below. According to the protocol, at a concentration of about 30 μM, neurotransmitters such as glutamic It causes at least about 50% inhibition of phosphate.   The compounds of the present invention include glutamate, dopamine, norepinephrine, glycine. , Including aspartate and serotonin, especially glutamate The release of the substance can be modulated.   In addition, the compound of the present invention is also effective in neurotransduction as demonstrated in Example 64 below. A typical PCP and sigma while at the same time being an effective modulator of release Relatively low for PCP and / or sigma receptors in receptor binding assay Shows a good affinity. This is because the compounds of the present invention are directed against PCP or sigma receptors. Has a distinctly different therapeutic mechanism compared to neuroprotective agents that show high affinity Suggests.   Suitable compounds of the invention, including compounds of formula I, IA, IB, IIA or IIB Halogen groups are F, Cl, Br and I. A preferred alkyl group is methyl , Ethyl, n-propyl, iso-propyl, n-butyl, tert-butyl, iso 1 to about 12, such as -butyl, sec-butyl, pentyl and hexyl groups, More preferably, those having 1 to about 6 carbon atoms are included. Preferred alkenyl And alkynyl groups are one or more unsaturated bonds, preferably 1 or 2 unsaturated bonds. 2 to about 12, more preferably 2 to about 6, and even more preferably 2 to about 3. Or a group having 4 carbon atoms. As used herein, "alkyl", “Alkenyl” and “alkynyl” each refer to both cyclic and acyclic Say. However, linear or branched acyclic groups are generally more preferred. Preferred alkoxy groups of the compounds of this invention contain one or more oxygen bonds and 1 to about 12 carbon atoms. , More preferably 1 to about 8 and even more preferably 1 to about 6 carbon atoms. Including groups that Preferred alkylthio groups have 1 or more thioether bonds and 1 To about 12, more preferably 1 to about 8, and still more preferably 1 to about 6 carbon sources. And a group having a child. Preferred aminoalkyl groups are one or more primary, secondary Primary and / or tertiary amino groups and 1 to about 12, more preferably 1 to about 8 More preferably 1 to about 6 and even more preferably 1 to 3 carbon atoms. Including groups that Secondary and tertiary amino groups are more commonly preferable. Preferred alkylsulfinyl groups are 1 or more, more typically 1 And a sulfinyl (SO) group of 1 to about 12, more preferably 1 to about 6, Preferably having 1 to 3 carbon atoms. Preferred alkylsulfonyl groups are One or more, more typically one sulfono (SO₂) Groups, 1 to about 12, and more Preferably 1 to about 6 carbons, more preferably 1 to 3 carbons With atoms. Suitable heteroaromatic or heteroaryl compounds of the invention And heteroalicyclic groups are 1-3 separate rings or fused rings and one or more N, A quinolyl containing an O or S atom and including, for example, 8-quinolinyl, 5- Indolinyl, including indolinyl, furyl, thienyl, pyrrolyl, thiazolin , Pyridyl, pyrimidinyl, pyridazinyl, oxazolyl and phthalimide Groups (all of which are independent rings, fused rings with further cyclic groups (eg benzene Fused to the zen ring, optionally substituted at one or more possible positions), Rabi substituted or unsubstituted tetrahydrofuranyl, tetrahydrofuranyl, Peridinyl, piperazinyl, morpholino, pyrrolidinyl, pyrazinyl, coumarini , Tetrahydroquinolinyl, tetrahydroisoquinolinyl, benzothiazolyl , Benzotriazolyl and benzimidazolyl. Carbocyclic aryl Preferred aryl groups included in the group are from about 5 to about 20 carbons, more preferably Phenyl, naphthyl, acenaphthyl, phenanthryl, anthracyl and full About 1 to 3 monocyclic or fused rings, such as the orene group, and 6 to about 18 carbon atoms And those having and.   The substituted moieties of the compounds of the invention may have one or more possible positions in one or more suitable positions. Groups such as halogens as F, Cl, Br or I; cyano; Sil; nitro; azide; carboxy; carbocyclic aryl; 1 to about 12 or 1 ~ An alkyl group, including an alkyl group having about 6 carbon atoms; one or more unsaturated bonds And alkenyl containing groups having 2 to about 12 or 2 to about 6 carbon atoms. And alkynyl groups; alkoxy groups, such as one or more oxygen bonds, and 1 to about 1 Groups having 2 or 1 to about 6 carbon atoms; alkylthio groups, eg 1 Having the above thioether bonds and 1 to about 12 or 1 to 6 carbon atoms Group; aminoalky Group, for example one or more N atoms and 1 to about 12 or 1 to about 6 carbon atoms A group having and an aminoalkylene aryl group, eg having one or more N atoms , Whose N atom is by one or more alkylenearyl groups such as benzyl and the like. A particularly preferred substituent of the phenyl or other aryl group that is substituted is dibenzyl Groups such as ruamino; alkylsulfinyl, eg one or more sulfines Groups having a nyl group and 1 to about 12 or 1 to about 6 carbon atoms; alkyls Rufonyl, such as one or more sulfono groups and 1 to about 12 or 1 to about 6 It may be substituted with a group having a carbon atom. Further preferred compounds Substituents are disclosed herein.   Particularly preferred substituents are preferably 1 to about 12 or 1 to about 6 carbon atoms. Carboxylic acyl having, ie acetyl, propanoyl, isopropano Noyl, butanoyl, sec-butanoyl, pentanoyl and hexanoyl groups Such alkanoyl groups are included. Equally preferred substituents are monocyclic and polycyclic. Aralkyl groups comprising separate and / or fused aryl groups, For example, the above aryl group is one or more C₁~ C₁₂, C₁~ C₆Or C₁~ C_FourA Substituted by alkyl groups, eg phenylethyl, phenylpropyl , Phenylbutyl, phenylpentyl and phenylhexyl groups and them Is a branched chain isomer of. Also, such as haloalkyl, especially trifluoromethyl Fluoroalkyl is preferred. Aroyl group is also a preferable substituent, For example, phenyl, naphthyl, acenaphthyl, phenanthryl and anthracyl. A carbonyl substituted by an aryl group; and a carbonyl substituted by one or more aryl groups Substituted carboxylic acyl groups such as diphenylacetoxy and fluor It is a rencarboxy group. Also, the aralkanoyl group Preferably, it includes a carbonyl substituted by an aralkyl group, as described above. You. Further, an aralkoxy group is also a preferable substituent, and phenyl, naphthyl, Alkoxy substituted by acenaphthyl, phenanthyl and anthracyl groups Including a Si group. Preferred substituted aryl groups are the aryl groups mentioned above, especially halo, It includes phenyl substituted by droxy, alkoxy, amino and the like.   Particularly preferred substituents of the compounds of the invention are halogen, hydroxy, CF_Three, C₁ ~ C₆Acyl, C₁~ C₆Alkyl, C₂~ C₆Alkenyl, C₂~ C₆Alkynyl, C₁~ C₆Alkoxy, C₆~ C₁₈Aryl, C₂~ C₆Dialkoxymethyl, shea No, C_Three~ C₆Cycloalkyl, C_Three~ C₆Heterocycloalkyl, C_Three~ C_FifteenZia Rualkylaminoalkyl, carboxy, C₂~ C₆Carboxylic acid, carboxamide, C₁~ C₆Haloalkyl, C₁~ C₆Haloalkylthio, allyl, C₇~ C₂₀Aral Kill, C fused to benzene ring_Three~ C₆Heterocycloalkyl ring, C₁~ C₆Archi Ruthio, arylthio, C₁~ C₆Haloalkoxy, amino, C₁~ C₆Alkyria Mino, C₂~ C_FifteenDialkylamino, carbamoyl, C₁~ C₆N-alkylcal Bamoyl, C₂~ C_FifteenN, N-dialkylcarbamoyl, nitro, C₂~ C_FifteenZia It includes ruquilsulfamoyl and the like.   Particularly preferred R and R of compounds of the invention¹The groups include hydrogen and substituted and non-substituted Included are substituted alkyls, especially methyl, ethyl, propyl and butyl. hydrogen And methyl and ethyl are particularly preferred R and R¹Group.   Preferred R of the compound of the present invention²The group may be halo, substituted or unsubstituted alkyl, Substituted or unsubstituted aminoalkyl, substituted or unsubstituted alkoxy Ci, substituted or unsubstituted alkylthio and substituted or unsubstituted alkylsulfur Including finyl. Preferred substituted alkyl R²The group is fluoromethyl or fluoro. Halo groups including fluoroalkyl such as ethyl, especially trifluoromethyl. It is a rukyll group.   Typically preferred Ar substituents for compounds of formula I, IA, IB, IIA or IIB are: , Substituted and unsubstituted carboxyl groups, especially substituted and unsubstituted phenyl groups You. Particularly preferred is a phenyl group having 1 to 5 ring substituents, 1 ring substituent, For example, a phenyl group having a substituent at the 3 or 4 position; a disubstituted phenyl group, For example, 2,3-substituted phenyl group, 2,4-substituted phenyl group, 2,5-substituted phenyl group Group, 2,6-substituted phenyl group, 3,4-substituted phenyl group and 3,5-substituted phenyl group. Phenyl group; trisubstituted phenyl group such as 2,3,4-substituted phenyl group, 2,3, 5-substituted phenyl group, 2,3,6-substituted phenyl group and 3,4,5-substituted phenyl group Nyl group; tetra-substituted phenyl group, for example, 2,3,4,5-substituted phenyl group, 2,3 , 4,6-substituted phenyl groups and 2,3,5,6-substituted phenyl groups. Preferred ring substituents for such substituted phenyl Ar groups are halogen; nitro; Alkyl having about 8 carbon atoms, eg methyl, ethyl, propyl, butyl Ru, pentyl, hexyl, etc .; alkoxy having 1 to about 8 carbon atoms, Eg methoxy, ethoxy, propoxy, butoxy etc .; alkylthio, eg Includes methylthio and ethylthio; haloalkyls such as trifluoromethyl Containing fluoroalkyl, chloroalkyl and bromoalkyl; fluoroar Haloalkoxy, including Coxy, such as trifluoromethoxy, and charcoal Includes cyclic aryl, especially substituted or unsubstituted phenyl.   Specifically preferred Ar and / or in formula I, IA, IB, IIA or IIB Or Ar¹The group is halophenyl, such as 2,5-dibromophenyl, 4- Lolophenyl, 2,3-dichlorophenyl, 3,4-dichlorophenyl, 2,3 , 4-trichlorophenyl, 3,4,5-trichlorophenyl, 2,3,4,5 -Tetrachlorophenyl, 2,3,5,6-tetrachlorophenyl, 3-iodo Fluorophenyl, bromophenyl and iodophe, including phenyl and the like Nyl; alkylphenyl, such as 2,3-dimethylphenyl, 3-isopropylamine Te including ruphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl Cyclohexyl groups including rt-butylphenyl and 4-cyclohexylphenyl , Sec-Butylphenyl, including 4-sec-butylphenyl, 3-adamanti Adamantylphenyl including ruphenyl and 4-adamantylphenyl Th; Haloalkyl phenyl including fluoro, bromo and chloroalkyl phenyl Such as trifluoromethylphenyl, especially 4-trifluoromethylphenyl. Alkoxy; for example, 4-methoxyphenyl, 3,4-dimethoxy Phenyl, 4-n-butoxyphenyl, etc .; Nitrophenyl, such as 3-nit Rophenyl, 4-nitrophenyl, etc .; substituted and unsubstituted biphenyls, even 2-biphenyl, 3-biphenyl, 4-biphenyl, etc .; 1 to about 10 carbons An aralkylphenyl having an atom and an aryl substituent of phenyl, preferably Substituted and unsubstituted aralkylphenyls, including (1'-methyl-2 ′ -Phenylethyl) phenyl (ie C₆H_Five-CH₂CH (CH_Three) C₆H_Five− ), For example 3- (1′-methyl-2′-phenylethyl) phenyl and 4- (1'-methyl-2'-phenylethyl) phenyl, phenethylphenyl Wachi C₆H_FiveCH₂CH₂C₆H_Five-), For example 3-phenethylphenyl and 4- Phenethylphenyl, etc .; substituted and non-substituted An alternative aralkylaminophenyl, such as (monophenyl C_1-6Alkylene) Minophenyl or (diphenyl) C_1-6Alkylene) aminophenyl, even For example, (N, N-dibenzylamino) phenyl, (N, N-diphenetyleneamino) Phenyl, N-methyl-N-benzylaminophenyl and the like; substituted and unsubstituted Substituted and unsubstituted alkyl groups including phenoxyphenyl and benzyloxyphenyl. Lyloxyphenyl and aralkyloxyphenyl, such as 4-benzyl Oxyphenyl, 3-benzyloxyphenyl, dibenzyloxyphenyl, For example, 3-dibenzyloxyphenyl and 4-dibenzyloxyphenyl, etc. Substituted and unsubstituted (alkyleneoxyaryl) phenyl, eg (C_{1- 6} Alkyleneoxyaryl) phenyl, especially substituted and unsubstituted (C_1-6Archi Renoxyphenyl) phenyl, eg, one or more C_1-6Alkyl, halo- Halo C_1-6Ring placement of alkyl, alkoxy, alkylthio or nitrobenzyl Substituted or unsubstituted benzyloxyphenyl having a substituent; substituted and non-substituted Substituted heterocycle-substituted phenyl, especially heteroaromatic ring-substituted phenyl, eg indole Phenyl substituted by phenyl, such as 3- (2'-indole) phenyl or And 4- (2'-indole) phenyl, substituted by benzothiazole Phenyl, for example 3- (2'-benzothiazole) phenyl, 4- (2-ben Zothiazole) phenyl, 3- (2′-benzothiazole-6′-methyl) phen Nyl, 4- (2-benzothiazole-6'-methyl) phenyl and 5-yne One or more indolinyl including furyl, furyl, thienyl, pyrrolyl, thiazo Ryl, pyridyl, pyrimidinyl, pyridazinyl, oxazolyl and phthalimi Group (all of which are independently fused to a further cyclic group (eg 1 or more Phenyl, which may be substituted at any available position), and One or more substituted or unsubstituted tetrahydrofuranyl, tetrahydrofuranyl, Piperidinyl, piperazinyl, morpholino, pyrrolidinyl group, pyrazinyl, bear Linyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, benzothiazo Included is phenyl substituted by ryl and benzimidazolyl. Scripture Formally, the preferred heteroaromatic-substituted phenyl substituents are at one or more ring positions, More typically, one or two phenyl ring positions independently contain one to three rings. A ring containing 3 to 8 ring members in each ring and 1 to 3 N, O or S atoms. Includes phenyl substituents substituted with teloaromatic groups.   Suitable Ar and / or Ar of formula I, IA, IB, IIA or IIB¹Motohama Was Substituted and unsubstituted naphthyl and 3-acenaphthyl and 5-acenaphth Substituted and unsubstituted acenaphthyl, including tyl, are included.   As a particularly preferred compound of the present invention, Includes the following compounds:   N- (5-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) gua Herring;   N- (5-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N -Methylguanidine;   N- (5-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N ′ -Methylguanidine;   N- (5-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N , N'-dimethylguanidine;   N, N'-bis (5-acenaphthyl) -N-methylguanidine;   N, N'-bis (5-acenaphthyl) -N, N'-dimethylguanidi N;   N- (5-acenaphthyl) -N '-(1-anthracenyl) guanidine;   N- (5-acenaphthyl) -N '-(1-anthracenyl) -N-methylgua Herring;   N- (5-acenaphthyl) -N '-(1-anthracenyl) -N'-methyl group Anidine;   N- (5-acenaphthyl) -N '-(1-anthracenyl) -N, N'-Jime Tilguanidine;   N- (5-acenaphthyl) -N '-(4-tert-butylphenyl) guanidine ;   N- (5-acenaphthyl) -N '-(4-tert-butylphenyl) -N-methyl Luguanidine;   N- (5-acenaphthyl) -N '-(4-tert-butylphenyl) -N'-me Tilguanidine;   N- (5-acenaphthyl) -N '-(4-tert-putylphenyl) -N, N ' -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(4-cyclohexylphenyl) guanidi N;   N- (5-acenaphthyl) -N '-(4-cyclohexylphenyl) -N-me Tilguanidine;   N- (5-acenaphthyl) -N '-(4-cyclohexylphenyl) -N'- Methylguanidine;   N- (5-acenaphthyl) -N '-(4-cyclohexylphenyl) -N, N ′ -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(4-sec-putylphenyl) guanidine ;   N- (5-acenaphthyl) -N '-(4-sec-butylphenyl) -N-methyl Luguanidine;   N- (5-acenaphthyl) -N '-(4-sec-butylphenyl) -N'-me Tilguanidine;   N- (5-acenaphthyl) -N '-(4-sec-butylphenyl) -N, N ' -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(4-methoxyphenyl) guanidine;   N- (5-acenaphthyl) -N '-(4-methoxyphenyl) -N-methyl group Anidine;   N- (5-acenaphthyl) -N '-(4-methoxyphenyl) -N'-methyl Guanidine;   N- (5-acenaphthyl) -N '-(4-methoxyphenyl) -N, N'-di Methylguanidine;   N- (5-acenaphthyl) -N '-(2 3-dichlorophenyl) guanidine ;   N- (5-acenaphthyl) -N '-(2 3-dichlorophenyl) -N-methyl Luguanidine;   N- (5-acenaphthyl) -N '-(2 3-dichlorophenyl) -N'-me Tilguanidine;   N- (5-acenaphthyl) -N '-(2 3-dichlorophenyl) -N, N ' -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(4-methoxy-2-naphthyl) g Anidine;   N- (5-acenaphthyl) -N '-(4-methoxy-2-naphthyl) -N-me Tilguanidine;   N- (5-acenaphthyl) -N '-(4-methoxy-2-naphthyl) -N'- Methylguanidine;   N- (5-acenaphthyl) -N '-(4-methoxy-2-naphthyl) -N, N ′ -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(3 4-dichlorophenyl) guanidine ;   N- (5-acenaphthyl) -N '-(3 4-dichlorophenyl) -N-methyl Luguanidine;   N- (5-acenaphthyl) -N '-(3 4-dichlorophenyl) -N'-me Tilguanidine;   N- (5-acenaphthyl) -N '-(3 4-dichlorophenyl) -N, N ' -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(4-chlorophenyl) guanidine;   N- (5-acenaphthyl) -N '-(4-chlorophenyl) -N-methylgua Herring;   N- (5-acenaphthyl) -N '-(4-chlorophenyl) -N'-methyl group Anidine;   N- (5-acenaphthyl) -N '-(4-chlorophenyl) -N, N'-Jime Tilguanidine;   N- (5-acenaphthyl) -N '-(2-naphthyl) guanidine;   N- (5-acenaphthyl) -N '-(2-naphthyl) -N-methylgua Nijin:   N- (5-acenaphthyl) -N '-(2-naphthyl) -N'-methylguanidi N;   N- (5-acenaphthyl) -N '-(2-naphthyl) -N, N'-dimethyl group Anidine;   N- (5-acenaphthyl) -N '-(6-quinolinyl) guanidine;   N- (5-acenaphthyl) -N '-(6-quinolinyl) -N-methylguanidi N;   N- (5-acenaphthyl) -N '-(6-quinolinyl) -N'-methylguani gin;   N- (5-acenaphthyl) -N '-(6-quinolinyl) -N, N'-dimethyl Guanidine;   N- (5-acenaphthyl) -N '-(4-nitrophenyl) guanidine;   N- (5-acenaphthyl) -N '-(4-nitrophenyl) -N-methylgua Herring;   N- (5-acenaphthyl) -N '-(4-nitrophenyl) -N'-methyl group Anidine;   N- (5-acenaphthyl) -N '-(4-nitrophenyl) -N, N'-Jime Tilguanidine;   N- (5-acenaphthyl) -N '-(3-biphenyl) guanidine;   N- (5-acenaphthyl) -N '-(3-biphenyl) -N-methylguanidi N;   N- (5-acenaphthyl) -N '-(3-biphenyl) -N'-methylguani gin;   N- (5-acenaphthyl) -N '-(3-biphenyl) -N, N'-dimethyl Guanidine;   N- (5-acenaphthyl) -N '-(2 3-dimethylphenyl) guanidine ;   N- (5-acenaphthyl) -N '-(2 3-dimethylphenyl) -N-methyl Luguanidine;   N- (5-acenaphthyl) -N '-(2 3-dimethylphenyl) -N'-me Tilguanidine;   N- (5-acenaphthyl) -N '-(2 3-dimethylphenyl) -N, N ' -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(2-biphenyl) guanidine;   N- (5-acenaphthyl) -N '-(2-biphenyl) -N-methylguanidi N;   N- (5-acenaphthyl) -N '-(2-biphenyl) -N'-methylguani gin;   N- (5-acenaphthyl) -N '-(2-biphenyl) -N, N'-dimethyl Guanidine;   N- (5-acenaphthyl) -N '-(2 5-dibromophenyl) guanidine ;   N- (5-acenaphthyl) -N '-(2 5-dibromophenyl) -N-methyl Luguanidine;   N- (5-acenaphthyl) -N '-(2 5-dibromophenyl) -N'-me Tilguanidine;   N- (5-acenaphthyl) -N '-(2 5-dibromophenyl) -N, N ' -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(3 4-dimethoxyphenyl) guanidi N;   N- (5-acenaphthyl) -N '-(3 4-dimethoxyphenyl) -N-me Tilguanidine;   N- (5-acenaphthyl) -N '-(3 4-dimethoxyphenyl) -N'- Methylguanidine;   N- (5-acenaphthyl) -N '-(3 4-dimethoxyphenyl) -N, N ′ -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(4-methoxy-1-naphthyl) -N-me Tilguanidine;   N- (5-acenaphthyl) -N '-(4-methoxy-1-naphthyl) -N'- Methylguanidine;   N- (5-acenaphthyl) -N '-(4-methoxy-1-naphthyl) -N, N ′ -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(4-chloro-1-naphthyl) guanidine ;   N- (5-acenaphthyl) -N '-(4-chloro-1-naphthyl) -N-methyl Luguanidine;   N- (5-acenaphthyl) -N '-(4-chloro-1-naphthyl) -N'-me Tilguanidine;   N- (5-acenaphthyl) -N '-(4-chloro-1-naphthyl) -N, N ' -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) gua Herring;   N- (5-acenaphthyl) -N '-(3 4, 5-trichloropheny ) -N-methylguanidine;   N- (5-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) -N ′ -Methylguanidine;   N- (5-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) -N , N'-dimethylguanidine;   N- (5-acenaphthyl) -N '-(4-biphenyl) guanidine;   N- (5-acenaphthyl) -N '-(4-biphenyl) -N-methylguanidi N;   N- (5-acenaphthyl) -N '-(4-biphenyl) -N'-methylguani gin;   N- (5-acenaphthyl) -N '-(4-biphenyl) -N, N'-dimethyl Guanidine;   N- (5-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl ) Guanidine;   N- (5-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl ) -N-Methylguanidine;   N- (5-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl ) -N'-methylguanidine;   N- (5-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl ) -N, N'-dimethylguanidine;   N- (5-acenaphthyl) -N '-(3-isopropylphenyl) guanidine ;   N- (5-acenaphthyl) -N '-(3-isopropylphenyl) -N-methyl Luguanidine;   N- (5-acenaphthyl) -N '-(3-isopropylphenyl)- N'-methylguanidine;   N- (5-acenaphthyl) -N '-(3-isopropylphenyl) -N, N ' -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(3-tert-butylphenyl) guanidine ;   N- (5-acenaphthyl) -N '-(3-tert-butylphenyl) -N-methyl Luguanidine;   N- (5-acenaphthyl) -N '-(3-tert-butylphenyl) -N'-me Tilguanidine;   N- (5-acenaphthyl) -N '-(3-tert-butylphenyl) -N, N ' -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl ) Guanidine;   N- (5-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl ) -N-Methylguanidine;   N- (5-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl ) -N'-methylguanidine;   N- (5-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl ) -N, N'-dimethylguanidine;   N- (5-acenaphthyl) -N '-(3-iodophenyl) guanidine;   N- (5-acenaphthyl) -N '-(3-iodophenyl) -N-methylgua Herring;   N- (5-acenaphthyl) -N '-(3-iodophenyl) -N'-methyl group Anidine;   N- (5-acenaphthyl) -N '-(3-iodophenyl) -N, N'-Jime Tilguanidine;   N- (5-acenaphthyl) -N '-(3-nitrophenyl) guanidine;   N- (5-acenaphthyl) -N '-(3-nitrophenyl) -N-methylgua Herring;   N- (5-acenaphthyl) -N '-(3-nitrophenyl) -N'-methyl group Anidine;   N- (5-acenaphthyl) -N '-(3-nitrophenyl) -N, N'-Jime Tilguanidine;   N- (5-acenaphthyl) -N '-(5-indolinyl) guanidine;   N- (5-acenaphthyl) -N '-(5-indolinyl) -N-methylguani gin;   N- (5-acenaphthyl) -N '-(5-indolinyl) -N'-methylgua Herring;   N- (5-acenaphthyl) -N '-(5-indolinyl) -N, N'-dimethy Luguanidine;   N- (5-acenaphthyl) -N '-(3-acenaphthyl) guanidine;   N- (5-acenaphthyl) -N '-(3-acenaphthyl) -N-methylguani gin;   N- (5-acenaphthyl) -N '-(3-acenaphthyl) -N'-methylgua Herring;   N- (5-acenaphthyl) -N '-(3-acenaphthyl) -N, N'- Dimethylguanidine;   N- (5-acenaphthyl) -N '-(2-fluorenyl) guanidine;   N- (5-acenaphthyl) -N '-(2-fluorenyl) -N-methylguani gin;   N- (5-acenaphthyl) -N '-(2-fluorenyl) -N'-methylgua Herring;   N- (5-acenaphthyl) -N '-(2-fluorenyl) -N, N'-dimethy Luguanidine;   N- (5-acenaphthyl) -N '-(4-n-butoxyphenyl) guanidine ;   N- (5-acenaphthyl) -N '-(4-n-butoxyphenyl) -N-methyl Luguanidine;   N- (5-acenaphthyl) -N '-(4-n-butoxyphenyl) -N'-me Tilguanidine;   N- (5-acenaphthyl) -N '-(4-n-butoxyphenyl) -N, N ' -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl ) Guanidine;   N- (5-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl ) -N-Methylguanidine;   N- (5-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl ) -N'-methylguanidine;   N- (5-acenaphthyl) -N '-(3- (2-methoxy) -dibenzofurani Le) -N, N'-dimethylguanidine;   N- (5-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl) g Anidine;   N- (5-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl)- N-methylguanidine;   N- (5-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl)- N'-methylguanidine;   N- (5-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl)- N, N'-dimethylguanidine;   N- (5-acenaphthyl) -N '-(4-trifluoromethylphenyl) gua Herring;   N- (5-acenaphthyl) -N '-(4-trifluoromethylphenyl) -N -Methylguanidine;   N- (5-acenaphthyl) -N '-(4-trifluoromethylphenyl) -N ′ -Methylguanidine;   N- (5-acenaphthyl) -N '-(4-trifluoromethylphenyl) -N , N'-dimethylguanidine;   N- (5-acenaphthyl) -N '-(4-methylthiophenyl) guanidine;   N- (5-acenaphthyl) -N '-(4-methylthiophenyl) -N-methyl Guanidine;   N- (5-acenaphthyl) -N '-(4-methylthiophenyl) -N'-methyl Luguanidine;   N- (5-acenaphthyl) -N '-(4-methylthiophenyl) -N, N'- Dimethylguanidine;   N- (5-acenaphthyl) -N '-(3-sec-butylphenyl) gua Herring;   N- (5-acenaphthyl) -N '-(3-sec-butylphenyl) -N-methyl Luguanidine;   N- (5-acenaphthyl) -N '-(3-sec-butylphenyl) -N'-me Tilguanidine;   N- (5-acenaphthyl) -N '-(3-sec-butylphenyl) -N, N ' -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) gua Herring;   N- (3-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N -Methylguanidine;   N- (3-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N ′ -Methylguanidine;   N- (3-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N , N'-dimethylguanidine;   N, N'-bis (3-acenaphthyl) -N-methylguanidine;   N, N'-bis (3-acenaphthyl) -N, N'-dimethylguanidine;   N- (3-acenaphthyl) -N '-(1-anthracenyl) guanidine;   N- (3-acenaphthyl) -N '-(1-anthracenyl) -N-methylgua Herring;   N- (3-acenaphthyl) -N '-(1-anthracenyl) -N'-methyl group Anidine;   N- (3-acenaphthyl) -N '-(1-anthracenyl) -N, N'-dimethylguanidine;   N- (3-acenaphthyl) -N '-(4-tert-butylphenyl) guanidine ;   N- (3-acenaphthyl) -N '-(4-tert-butylphenyl) -N-methyl Luguanidine;   N- (3-acenaphthyl) -N '-(4-tert-butylphenyl) -N'-me Tilguanidine;   N- (3-acenaphthyl) -N '-(4-tert-butylphenyl) -N, N ' -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(4-cyclohexylphenyl) guanidi N;   N- (3-acenaphthyl) -N '-(4-cyclohexylphenyl) -N-me Tilguanidine;   N- (3-acenaphthyl) -N '-(4-cyclohexylphenyl) -N'- Methylguanidine;   N- (3-acenaphthyl) -N '-(4-cyclohexylphenyl) -N, N ′ -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(4-sec-butylphenyl) guanidine ;   N- (3-acenaphthyl) -N '-(4-sec-putylphenyl) -N-methyl Luguanidine;   N- (3-acenaphthyl) -N '-(4-sec-butylphenyl) -N'-me Tilguanidine;   N- (3-acenaphthyl) -N '-(4-sec-butylphenyl) -N, N ' -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(4-methoxyphenyl) guanidine;   N- (3-acenaphthyl) -N '-(4-methoxyphenyl) -N-methyl group Anidine;   N- (3-acenaphthyl) -N '-(4-methoxyphenyl) -N'-methyl Guanidine;   N- (3-acenaphthyl) -N '-(4-methoxyphenyl) -N, N'-di Methylguanidine;   N- (3-acenaphthyl) -N '-(2 3-dichlorophenyl) guanidine ;   N- (3-acenaphthyl) -N '-(2 3-dichlorophenyl) -N-methyl Luguanidine;   N- (3-acenaphthyl) -N '-(2 3-dichlorophenyl) -N'-me Tilguanidine;   N- (3-acenaphthyl) -N '-(2 3-dichlorophenyl) -N, N ' -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(4-methoxy-2-naphthyl) guanidi N;   N- (3-acenaphthyl) -N '-(4-methoxy-2-naphthyl) -N-me Tilguanidine;   N- (3-acenaphthyl) -N '-(4-methoxy-2-naphthyl) -N'- Methylguanidine;   N- (3-acenaphthyl) -N '-(4-methoxy-2-naphthyl) -N, N ′ -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(3 4-dichlorophenyl) gua Herring;   N- (3-acenaphthyl) -N '-(3 4-dichlorophenyl) -N-methyl Luguanidine;   N- (3-acenaphthyl) -N '-(3 4-dichlorophenyl) -N'-me Tilguanidine;   N- (3-acenaphthyl) -N '-(3 4-dichlorophenyl) -N, N ' -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(4-chlorophenyl) guanidine;   N- (3-acenaphthyl) -N '-(4-chlorophenyl) -N-methylgua Herring;   N- (3-acenaphthyl) -N '-(4-chlorophenyl) -N'-methyl group Anidine;   N- (3-acenaphthyl) -N '-(4-chlorophenyl) -N, N'-Jime Tilguanidine;   N- (3-acenaphthyl) -N '-(2-naphthyl) guanidine;   N- (3-acenaphthyl) -N '-(2-naphthyl) -N-methylguanidine ;   N- (3-acenaphthyl) -N '-(2-naphthyl) -N'-methylguanidi N;   N- (3-acenaphthyl) -N '-(2-naphthyl) -N, N'-dimethyl group Anidine;   N- (3-acenaphthyl) -N '-(6-quinolinyl) guanidine;   N- (3-acenaphthyl) -N '-(6-quinolinyl) -N-methylguanidi N;   N- (3-acenaphthyl) -N '-(6-quinolinyl) -N'-methylguani gin;   N- (3-acenaphthyl) -N '-(6-quinolinyl) -N, N'-dimethyl Guanidine;   N- (3-acenaphthyl) -N '-(4-nitrophenyl) guanidine;   N- (3-acenaphthyl) -N '-(4-nitrophenyl) -N-methylgua Herring;   N- (3-acenaphthyl) -N '-(4-nitrophenyl) -N'-methyl group Anidine;   N- (3-acenaphthyl) -N '-(4-nitrophenyl) -N, N'-Jime Tilguanidine;   N- (3-acenaphthyl) -N '-(3-biphenyl) guanidine;   N- (3-acenaphthyl) -N '-(3-biphenyl) -N-methylguanidi N;   N- (3-acenaphthyl) -N '-(3-biphenyl) -N'-methylguani gin;   N- (3-acenaphthyl) -N '-(3-biphenyl) -N, N'-dimethyl Guanidine;   N- (3-acenaphthyl) -N '-(2 3-dimethylphenyl) guanidine ;   N- (3-acenaphthyl) -N '-(2 3-dimethylphenyl) -N-methyl Luguanidine;   N- (3-acenaphthyl) -N '-(2 3-dimethylphenyl) -N'-me Tilguanidine;   N- (3-acenaphthyl) -N '-(2 3-dimethylphenyl) -N, N ' -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(2-biphenyl) guanidine;   N- (3-acenaphthyl) -N '-(2-biphenyl) -N-methylguanidi N;   N- (3-acenaphthyl) -N '-(2-biphenyl) -N'-methylguani gin;   N- (3-acenaphthyl) -N '-(2-biphenyl) -N, N'-dimethyl Guanidine;   N- (3-acenaphthyl) -N '-(2 5-dibromophenyl) guanidine ;   N- (3-acenaphthyl) -N '-(2 5-dibromophenyl) -N-methyl Luguanidine;   N- (3-acenaphthyl) -N '-(2 5-dibromophenyl) -N'-me Tilguanidine;   N- (3-acenaphthyl) -N '-(2 5-dibromophenyl) -N, N ' -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(3 4-dimethoxyphenyl) guanidi N;   N- (3-acenaphthyl) -N '-(3 4-dimethoxyphenyl) -N-me Tilguanidine;   N- (3-acenaphthyl) -N '-(3 4-dimethoxyphenyl) -N'- Methylguanidine;   N- (3-acenaphthyl) -N '-(3 4-dimethoxyphenyl) -N, N ′ -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(4-methoxy-1-naphthyl) -N-me Tilguanidine;   N- (3-acenaphthyl) -N '-(4-methoxy-1-naphthyl) -N'- Methylguanidine;   N- (3-acenaphthyl) -N '-(4-methoxy-1-naphthyl) -N, N ′ -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(4-chloro-1-naphthyl) guanidine ;   N- (3-acenaphthyl) -N '-(4-chloro-1-naphthyl) -N-methyl Luguanidine;   N- (3-acenaphthyl) -N '-(4-chloro-1-naphthyl) -N'-me Tilguanidine;   N- (3-acenaphthyl) -N '-(4-chloro-1-naphthyl) -N, N ' -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) gua Herring;   N- (3-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) -N -Methylguanidine;   N- (3-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) -N ′ -Methylguanidine;   N- (3-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) -N , N'-dimethylguanidine;   N- (3-acenaphthyl) -N '-(4-biphenyl) guanidine;   N- (3-acenaphthyl) -N '-(4-biphenyl) -N-methylguanidi N;   N- (3-acenaphthyl) -N '-(4-biphenyl) -N'-methylguani gin;   N- (3-acenaphthyl) -N '-(4-biphenyl) -N, N'-dimethyl Guanidine;   N- (3-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl ) Guanidine;   N- (3-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl ) -N-Methylguanidine;   N- (3-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl ) -N'-methylguanidine;   N- (3-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl ) -N, N'-dimethylguanidine;   N- (3-acenaphthyl) -N '-(3-isopropylphenyl) guanidine ;   N- (3-acenaphthyl) -N '-(3-isopropylphenyl) -N-methyl Luguanidine;   N- (3-acenaphthyl) -N '-(3-isopropylphenyl) -N'-me Tilguanidine;   N- (3-acenaphthyl) -N '-(3-isopropylphenyl) -N, N ' -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(3-tert-butylphenyl) guanidine ;   N- (3-acenaphthyl) -N '-(3-tert-butylphenyl) -N-methyl Luguanidine;   N- (3-acenaphthyl) -N '-(3-tert-butylphenyl)- N'-methylguanidine;   N- (3-acenaphthyl) -N '-(3-tert-butylphenyl) -N, N ' -Dimethylguanidine;   N- (3-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl ) Guanidine;   N- (3-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl ) -N-Methylguanidine;   N- (3-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl ) -N'-methylguanidine;   N- (3-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl ) -N, N'dimethylguanidine;   N- (3-acenaphthyl) -N '-(3-iodophenyl) guanidine;   N- (3-acenaphthyl) -N '-(3-iodophenyl) -N-methylgua Herring;   N- (3-acenaphthyl) -N '-(3-iodophenyl) -N'-methyl group Anidine;   N- (3-acenaphthyl) -N '-(3-iodophenyl) -N, N'-Jime Tilguanidine;   N- (3-acenaphthyl) -N '-(3-nitrophenyl) guanidine;   N- (3-acenaphthyl) -N '-(3-nitrophenyl) -N-methylgua Herring;   N- (3-acenaphthyl) -N '-(3-nitrophenyl) -N'-methyl group Anidine;   N- (3-acenaphthyl) -N '-(3-nitrophenyl) -N, N'-Jime Tilguanidine;   N- (3-acenaphthyl) -N '-(5-indolinyl) guanidine;   N- (3-acenaphthyl) -N '-(5-indolinyl) -N-methylguani gin;   N- (3-acenaphthyl) -N '-(5-indolinyl) -N'-methylgua Herring;   N- (3-acenaphthyl) -N '-(5-indolinyl) -N, N'-dimethy Luguanidine;   N- (3-acenaphthyl) -N '-(2-fluorenyl) guanidine;   N- (3-acenaphthyl) -N '-(2-fluorenyl) -N-methylguani gin;   N- (3-acenaphthyl) -N '-(2-fluorenyl) -N'-methylgua Herring;   N- (3-acenaphthyl) -N '-(2-fluorenyl) -N, N'-dimethy Luguanidine;   N- (3-acenaphthyl) -N '-(4-n-butoxyphenyl) guanidine ;   N- (3-acenaphthyl) -N '-(4-n-butoxyphenyl) -N-methyl Luguanidine;   N- (3-acenaphthyl) -N '-(4-n-butoxyphenyl) -N'-me Tilguanidine;   N- (3-acenaphthyl) -N '-(4-n-butoxyphenyl)- N, N'-dimethylguanidine;   N- (3-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl ) Guanidine;   N- (3-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl ) -N-Methylguanidine;   N- (3-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl ) -N'-methylguanidine;   N- (3-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl ) -N, N'-dimethylguanidine;   N- (3-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl) g Anidine;   N- (3-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl)- N-methylguanidine;   N- (3-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl)- N'-methylguanidine;   N- (3-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl)- N, N'-dimethylguanidine;   N- (3-acenaphthyl) -N '-(4-trifluoromethylphenyl) gua Herring;   N- (3-acenaphthyl) -N '-(4-trifluoromethylphenyl) -N -Methylguanidine;   N- (3-acenaphthyl) -N '-(4-trifluoromethylphenyl) -N ′ -Methylguanidine;   N- (3-acenaphthyl) -N '-(4-trifluoromethylphenyl) -N , N'-dimethylguanidine;   N- (3-acenaphthyl) -N '-(4-methylthiophenyl) guanidine;   N- (3-acenaphthyl) -N '-(4-methylthiophenyl) -N-methyl Guanidine;   N- (3-acenaphthyl) -N '-(4-methylthiophenyl) -N'-methyl Luguanidine;   N- (3-acenaphthyl) -N '-(4-methylthiophenyl) -N, N'- Dimethylguanidine;   N- (3-acenaphthyl) -N '-(3-sec-butylphenyl) guanidine ;   N- (3-acenaphthyl) -N '-(3-sec-butylphenyl) -N-methyl Luguanidine;   N- (3-acenaphthyl) -N '-(3-sec-butylphenyl) -N'-me Tilguanidine;   N- (3-acenaphthyl) -N '-(3-sec-butylphenyl) -N, N ' -Dimethylguanidine;   N- (5-acenaphthyl) -N '-(4-benzyloxyphenyl) guanidi N;   N- (5-acenaphthyl) -N '-(3-benzyloxyphenyl) guanidi N;   N- (5-acenaphthyl) -N '-(3-sec-butylphenyl) guanidine ;   N- (5-acenaphthyl) -N '-(2-anthracenyl) guanidine;   N- (5-acenaphthyl) -N '-(3-phenethylphenyl) guani gin;   N- (5-acenaphthyl) -N '-(4-adamantylphenyl) guanidine ;   N- (5-acenaphthyl) -N '-(3-benzyloxyphenyl) -N'- Methylguanidine;   N- (5-acenaphthyl) -N '-(4-benzyloxyphenyl) -N'- Methylguanidine;   N- (5-acenaphthyl) -N '-(3-biphenyl) -N'-methylguani gin;   N- (5-acenaphthyl) -N '-(3- (1'-methyl-2'-phenylene Tyl) phenyl) guanidine;   N- (5-acenaphthyl) -N '-(3 4-tetralinylphenyl) guani gin;   N- (5-acenaphthyl) -N '-(7-benzyltetralinylphenyl) g Anidine;   N- (5-acenaphthyl) -N '-(3 4-dibenzyloxyphenyl) Anidine;   N- (5-acenaphthyl) -N '-(3- (1- (4-ethoxyphenyl) propyl) Ropil) phenyl) guanidine;   N- (5-acenaphthyl) -N '-(3- (N ", N "-dibenzylamino) Phenyl) guanidine;   N- (5-acenaphthyl) -N '-(3- (1'-benzylbutyl) phenyl ) Guanidine;   N- (5-acenaphthyl) -N '-(3- (4-tert-butylbenzoyloxy) Cimethyl) phenyl) guanidine;   N- (5-acenaphthyl) -N '-(2- (2-indolyl) phenyl) gua Herring;   N- (5-acenaphthyl) -N '-(3-bromophenyl) guanidine;   N- (5-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N , N'-dimethylguanidine;   N- (5-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N ′ -Methylguanidine;   N- (5-acenaphthyl) -N '-(4- (2'-benzothiazole-6'- Methyl) phenyl) guanidine;   N- (3-acenaphthyl) -N '-(4-benzoyloxyphenyl) guani gin;   N- (3-acenaphthyl) -N '-(3-benzoyloxyphenyl) guani gin;   N- (3-acenaphthyl) -N '-(3-sec-butylphenyl) guanidine ;   N- (3-acenaphthyl) -N '-(2-anthracenyl) guanidine;   N- (3-acenaphthyl) -N '-(3-phenethylphenyl) guaninno;   N- (3-acenaphthyl) -N '-(4-adamantylphenyl) guanidine ;   N- (3-acenaphthyl) -N '-(3-benzyloxyphenyl) -N'- Methylguanidine;   N- (3-acenaphthyl) -N '-(4-benzyloxyphenyl)- N'-methylguanidine;   N- (3-acenaphthyl) -N '-(3-biphenyl) -N'-methylguani gin;   N- (3-acenaphthyl) -N '-(3- (1'-methyl-2'-phenylene Tyl) phenyl) guanidine;   N- (3-acenaphthyl) -N '-(3 4-tetralinylphenyl) guani gin;   N- (3-acenaphthyl) -N '-(7-benzyltetralinylphenyl) g Anidine;   N- (3-acenaphthyl) -N '-(3- (1- (4-ethoxyphenyl) propyl) Ropil) phenyl) guanidine;   N- (3-acenaphthyl) -N '-(3- (N ", N "-dibenzylamino) Phenyl) guanidine;   N- (3-acenaphthyl) -N '-(3- (1'-benzylbutyl) phenyl ) Guanidine;   N- (3-acenaphthyl) -N '-(3- (4-tert-butylbenzoyloxy) Cimethyl) phenyl) guanidine;   N- (3-acenaphthyl) -N '-(2- (2-indolyl) phenyl) gua Herring;   N- (3-acenaphthyl) -N '-(3-bromophenyl) guanidine;   N- (3-acenaphthyl) -N '-(3 4-dibenzyloxyphenyl) Anidine;   N- (3-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N , N'-dimethylguanidine;   N- (3-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N ′ -Methylguanidine;   N- (3-acenaphthyl) -N '-(4- (2'-benzothiazole-6'- Methyl) phenyl) guanidine; And pharmacologically acceptable salts of these compounds.   Preferred further compounds are Having one or more ring substituents on the acenaphthyl group Including the above compound Especially, R as defined above for formulas IIA and IIB² It is a substituent.   Particularly preferred pharmaceutically acceptable salts of the above compounds are the same as those mentioned in Examples below. Compounds, and 3-acenaphthyl derivatives of these exemplified compounds, that is, A compound containing a 3-acenaphthyl group instead of the 5-acenaphthyl group is included. You.   The compounds of the present invention include amines, typically amine salts such as amine hydrochloride. It can be prepared by reacting with a randomly formed substituted cyanamide. You. S. R. Safer et al. Org. Chem., 13: 924 (1948); G. J. Durant et al. Med. Chem., 28: 1414 (1985); C. A. Maryanoff et al., J. Org. Chem., 51: 1882 (1986); M . P. Kavanaugh et al., Proc. Natl. Acad. Sci. USA, 85: 2844-2848 (1988); Web er et al., Proc. Natl. Acad. Sci. USA, 83: 8784-8788 (1986); W. J. Cressman Org. Syn. Coll., 3: 608-609 (1955); International application WO 91/12797 and PCT / US92 / 01. See 050.   More specifically, the synthesis of diaryl-substituted guanidines of the present invention is typically carried out by the reaction scheme- 1 (where Ar is as defined above) 3-acenaphthyl in a medium (eg, refluxing chlorobenzene or toluene) or Is a substituted acetamide such as 5-acenaphthyl cyanamide. This is done by condensing the salt of the arylamine with reel cyanamide. Shea Namides have the corresponding nitro-substituted aryls as shown in the reaction scheme below. And then processed with cyanogen bromide. Can be.   In step 1 of the above reaction scheme, 5- and 3-nitroacenaphthene are H₂Oh And under a suitable pressure such as 40 psi in a suitable solvent such as ethyl acetate. The amine obtained by reduction with Pd / C is separated, for example by recrystallization. Engineering In step 2, the desired aminoacenaphthene was prepared in a suitable solvent such as ethyl acetate. Treated with cyanogen bromide, N-acenaphthyl cyanamide and acenaphthyl amine The hydrobromide salt is obtained. Then, the cyanamide is treated with refluxing chlorobenzene or toluene. Reaction with a substituted arylamine salt in a suitable heated solvent such as ruene to give the final product Obtain a product.   The tri- and tetra-substituted guanidines of the present invention are as outlined in Scheme-2 above. May be manufactured. As shown in the formula, (preferably prepared as described above N-5-acenaphthyl-N-alkylcyanamide or N-3-acenaphth Aryl cyanamide, such as tyl-N-alkyl cyanamide, is treated with AlCl_Threecatalyst In the presence of a suitable solvent such as chlorobenzene (of tri-substituted guanidine Salts of arylamines (for synthesis), or of tetra-substituted guanidines (for synthesis) For treatment) with a salt of N-alkylarylamine. The product is Purify by conventional methods such as rotography.   In the above reaction formula, the reaction of unsubstituted acenaphthyl cyanamide is shown. The acenaphthyl cyanamide having one or more ring substituents is reacted with the above-mentioned reaction formula-1. By reacting with a salt of an arylamine by the same procedure as described in 2 and 2, To obtain compounds of the present invention having a substituted acenaphthyl moiety, including compounds of . Such substituted cyanamide reagents can be easily It can be manufactured. For example, nitrating a substituted acenaphthyl derivative ( For example, HNO_Three/ H₂SO_FourWith one or more additional ring substituents) Obtain 3-nitroacenaphthyl or 5-nitroacenaphthyl. M.D.Vareny et al. J. Med. Chem., 35: 671 (1992). 2 or more differences due to nitration If the product is formed, the reaction product is separated by recrystallization or chromatography. be able to. Thereafter, such substituted nitro derivatives are converted to amines by hydrogenation. This amine can then be converted to cyanogen bromide and Reaction with an arylamine gives compounds of formula IIA or IIB. This way Suitable substituted acenaphthyl derivatives that can be nitrated with and further reacted are, for example: Including those mentioned above. 3-fluoroacenaphthalene, 3-chloroacenaphthalene , 3-bromoacenaphthalene, 4-fluoroacenaphthalene, 4-chloroacena Haloacenaphthalene such as phthalene and 4-bromoacenaphthalene; 4-a Alkanoylacenaphthalene such as cetylacenaphthalene; 4-methoxyacetate Alkoxyacenaphthalenes such as naphthalene; acenaphthalenes, 3-acids; 5-acenaphthalene, ethanol; 5-acenaphthalene, methanol; 3- (1 -Alkenylacenaphthalene such as -methylpropenyl) acenaphthalene; 5- Asenaphthalene carboxyanilide etc.   The ring substituents on the acenaphthyl derivative can be linked to potential functionalities in the reaction (eg, nitro Suitable protection if it contains unsaturated carbon-carbon bonds which can be reduced during the hydrogenation of Groups can be used, but this protecting group is then known to those skilled in the synthetic art. Removed as is known.   In addition to nitration of substituted acenaphthyl derivatives, compounds of formula IIA or IIB are included. The compounds of the invention having a substituted acenaphthyl moiety are Can be prepared by any method. Specifically, an amine or amine precursor group and To prepare other acenaphthyl derivatives having one or more further ring substituents Is V. N. Komissarov, Zh. Org. Khim., 26 (5): 1106-10 (1990); Skulski et al. , Pol. J. Chem., 55 (9): 1809-24 (1981); F. Pozharskii, Isobret. Prom. O braztsy, Tovarnye Znaki, (3), 96-7 (1982); P. Li et al., US 78890736 (1978); N. S. Vorozhtsov, Zh. Org. Khim., 8 (2): 353-7 (1972); Wolinski et al., Rocz . Chem., 44 (9): 1721-31 (1970); A. P. Karishin et al., Zh. Obshch. Khim., 39 (9) : 2098-101 (1969); and V. V. Mezheritskii et al., Zh. Org. Khim., 27 (10): 2198- 204 (1991).   Compounds prepared in this way are converted, if necessary, to amines and then The substituted acenaphthyl moiety is reacted with CNBr and an arylamine as described above. A guanidine derivative having is obtained.   As mentioned above, the N, N′-diaryl-substituted guanidines of the present invention are unique Useful for many therapeutic applications, including treatment of diseases caused by degeneration of the transmitter system Thus, this disease can be treated with one or more substituted guanazines of the present invention. As mentioned above, the degeneration of neurotransmitter release can be associated with inhibition of neurotransmitter release, neurotransmission. Synergistic release of substances or time-dependent release of neurotransmitters from neuronal tissue Including either increase or decrease. Can be modulated by the compounds of the invention Neurotransmitters include glutamate, dopamine, norepinephrine, glycine, and Includes, but is not limited to, sparagate and serotonin. Skilled person Simply describes the method disclosed herein or in PCT / US92 / 01050. Used in conjunction with routine experimental methods, effective or particularly effective modulation of neurotransmitters. These compounds that are prepared products can be selected. For example, neuron death Compounds for the prevention of inflammation are associated with one or more variants of the rat middle cerebral artery occlusion model. And can be evaluated in vivo. Such models are usually used in strokes. In particular, it is considered to herald a neuroprotective effect. Ginsburg et al., Stroke, 20 : 1627-1642 (1989). Regarding the efficacy of major compounds, Evaluation can be performed using a 4-tube block model. Pulsinelli et al., Stroke: 19: 913-941 ( 1988) and PCT / US92 / 01050.   In particular, the present invention relates to neurological conditions such as epilepsy, neurodegenerative conditions and / or Is, for example, hypoxia, hypoglycemia, brain or spinal cord ischemia, brain or spinal cord injury, brain Treatment of nerve cell death due to stroke, heart attack, drowning, or carbon monoxide poisoning And / or provide a method for prevention. The heart is a typical candidate for treatment Patients with stroke, stroke, brain or spinal cord injury, severe ischemia is a potential complication Patients who have undergone surgery and those who have decompression sickness due to gas embolism in the bloodstream. Examples include patients like Iber.   The present invention also provides for administering a therapeutically effective amount of one or more compounds of the present invention. Thus, treating and / or treating various neurodegenerative diseases in subjects such as animals, especially humans. Provide a way to prevent. A typical God who can be treated and / or prevented Transgenerations include Parkinson's disease, Huntington's chorea, amyotrophic lateral sclerosis, and Zheimer's disease, Down syndrome, Korsakoff's disease, Olive pontine cerebellar atrophy, HIV- Includes induced dementia and blindness, or multi-infarct dementia. Dreyer et al., Science, 248: 3. As disclosed in 64-367 (1990), gp120 neurotoxicity is associated with NMDA receptor Ca explicitly mediated by excitatory amino acids bound at body sites²⁺Increased Associated with the bell. I don't want to be bound by theory again, , The present invention Compound prevents HIV-induced dementia by preventing the release of excess glutamate. And has utility in treating blindness.   As described above, the present invention provides treatment of Korsakoff's disease and chronic alcoholism-induced symptoms. In treatment, an effective amount of one or more compounds of the present invention is administered to a mammal, especially a human. There is provided a method of treating such a disease, which comprises administering to a subject. NMDA antagonist MK-801 (Merck Index, major thesis 3392, 11th edition, 1 989) was used to pretreat the animals in a rat model of Korsakoff's disease. , The degree of cell loss, hemorrhage and amino acid changes are significantly attenuated. P.J. Langlais Et al., Soc. Neurosci. See Abstr., 14: 774 (1988). Therefore, the book The compounds of the invention are associated with cell loss, hemorrhage and amino acids associated with Korsakoff's disease. Useful for change.   At least some of the compounds of the present invention were tested as described in Example 66 below. Shows that treatment of conditions treatable by blockade of voltage-activated sodium channels. It may be useful for treatment or prevention. Therefore, the present invention provides an effective amount of the present invention. Compounds, mammalian cells such as neuronal cells, especially human neuronal cells Of blocking effective voltage-sensitive sodium channels in Escherichia coli Methods are provided that include administering a compound, particularly to a mammal in need of such treatment. I do. Symptoms treatable by blockade of sodium channels include, for example, epilepsy. including. In addition, some compounds of the present invention impair presynaptic calcium channels. In addition, it will block sodium channels. Two of these potential effects are Particularly desirable for neuroprotective therapy.   NMDA Antagonists That Do Not Cross the Blood / Brain Barrier Have Certain Needs for Chemotherapy for Cancer Used to reduce adverse side effects such as nausea and vomiting (A. Fink-Jensen et al., Neurosci. Lett., 137 (2): 173). (1992)).   Similarly, Price, M.t. Et al., Soc. Neurosci. Abstr., 16: 377, abstr. 161.16 ( See also 1990). A compound of the invention, especially for example a pharmaceutically acceptable salt Compounds that are packed in the form of, and otherwise one or more polar functionalities ( Such as carboxy, amino, hydroxy, etc.) Certain compounds may have a relatively limited ability to cross the blood / brain barrier. Wear. Therefore, the compounds of the present invention, in particular the filled or not of the present invention, Thus, hydrophilic compounds of the present invention, which have limited blood-brain barrier permeability, are chemically Chemotherapy, especially cancer, that may be experienced by the mammal being treated, especially humans. It may be clinically useful in ameliorating the side effects associated with chemotherapy. Book The compounds of the invention will typically be administered to a subject in combination with a chemotherapy regimen. There will be.   The compounds of the invention may be used in therapy with other agents. For example For the treatment of stroke victims, one or more compounds of the invention may be added to streptokiners. Targeting interactions in blood coagulation such as ze, TPA and urokinase It may be suitably administered with a drug.   The compounds of the invention may be administered intranasally, orally or by injection, eg intramuscularly, intraperitoneally, subcutaneously. Alternatively, it can be given by intravenous infusion, or transdermal, intraocular or enteral administration. Optimal doses can be determined by conventional methods, including the assays of Examples 64-65 below. The guanidine of the present invention is produced by the method described in Examples below, for example, organic acid. Alternatively, a pharmaceutically acceptable salt of an inorganic acid (eg, hydrochloride, hydrobromide, sulfur Acid salt, hemisulfate, mesylate, gluconate, phosphate, nitrate, acetate, Urate, citrate, malein Acid, etc., and is suitably administered to the subject in protonated and water-soluble forms .   The compounds of the present invention may be administered alone or in combination with one or more therapeutic agents described above. It does not adversely react with the usual excipients, i.e. active compounds, and is not harmful to its receptor. Suitable for parenteral, enteral or intranasal application, a pharmaceutically acceptable organic or It can be used as a pharmaceutical composition by mixing with an inorganic carrier material. Preferred pharmaceutical Acceptable carriers include salt solutions, alcohols, vegetable oils, polyethylene glycols. , Gelatin, lactose, amylose, magnesium stearate, talc , Silicic acid, sticky paraffin, perfume oil, fatty acid monoglyceride and diglyceride , Petroleum ether fatty acid ester, hydroxymethyl cellulose, polyvinyl pyro Redon, but not limited to these. The drug can be sterilized, and If desired, auxiliary substances which do not deleteriously react with the active compounds, such as lubricants, preservatives, safety agents. Fixatives, humectants, emulsions, salts that affect osmotic pressure, buffers, colorants, seasonings and And / or can be mixed with fragrances and the like.   For parenteral application, solutions, preferably oily or aqueous solutions, may be suspensions, emulsions. Or, it is particularly suitable as well as an implant containing a suppository. Ampoules are convenient single It is a low dose.   For enteral administration, tablets with talc and / or carbohydrate carrier binders, Dragees or capsules are particularly suitable, the carrier preferably being lactose and And / or corn starch and / or potato starch are preferred . Syrups, elixirs, etc. can be used when using sweetening excipients. Wear. Sustained-release compositions include coatings in which the active ingredients can differentially disintegrate, such as Formulated to be protected by microencapsulation, multiple coatings, etc. Can be.   Intravenous or parenteral administration, eg subcutaneous, intraperitoneal or intramuscular administration, is usually preferable.   The actual preferred amount of active compound used in a given therapy will be utilized Specific compound, specific composition to be formulated, mode of application, specific site of administration, subject It should be understood that it varies depending on the weight, age, general health of the U.   The optimal dosing rate for a given dosing protocol should be based on the guidance criteria above. Can be readily ascertained by one skilled in the art using conventional dose-finding tests as described above. In general, one Suitable effective amounts of one or more compounds of general formula I, IA, IB, IIA or IIB are When using a more potent compound of general formula I, IA, IB, IIA or IIB for 0.5 to 50 mg / kg body weight of the receptor per day, preferably 1 / day It is in the range of 1 to 10 mg per 1 kg of body weight. The desired procedure is once a day, or a number 1 divided dose, for example 2 to 4 divided doses at appropriate intervals during the day, or Other suitable dosing regimens are suitably administered. Such divided doses are, for example, in units 0.25-25 mg of compound of general formula I, IA, IB, IIA or IIB per dose, Preferably it can be administered as a unit dose form containing 0.5-5 mg per unit dose You.   Conventional guanidines as described in US Pat. No. 1,411,713 Similarly, the guanidines of the present invention could be used as vulcanization accelerators.   All documents mentioned in this specification are herein incorporated by reference in their entirety. Included.   The present invention is further described by the following examples, which show Interpreted as limiting the understanding of the Should not be. General description   All percentages given in the examples below are weight unless otherwise indicated. The amount is%. All temperatures are given in degrees Celsius.   Melting points are measured in open capillaries on a Thomas-Hoover device. , Made no modifications. Thin layer chromatography is Merck Silica Gel 60F_{twenty five Four} (0.2 mm) or Baker-flex 1B2-F silica gel plate. Guanisi 254 nM UV light or bromocresol spray reagent (Sigma Chem ical Co.) and visualized on TLC as blue spots. Preparative TLC Is a silica gel (1,000 μm) glass that has been previously treated with Analtech GF. It was carried out on a backing board (20 × 20 cm). IR of all compounds,¹H and¹³C NM The R spectra were consistent with their defined structure. The NMR spectrum is Ge Chemistry recorded on neral Electric QE-300 or Varian Gemini 300 Transfer is performed by using a deuterated solvent (CHCl_Three, Δ7.26; CHD₂OD, δ3.30) The residual signal is shown in ppm (δ). Infrared spectrum is Nicolet 5DX On the B FT-IR or Perkin-Elmer model 1420 (unless otherwise indicated ) CHCl_ThreeI recorded inside. For all of the novel compounds, C, H and N Analysis was performed by either elemental analysis or accurate mass spectrometry. Accurate mass spectrometry The compound obtained was further analyzed by HPLC and / or 300 MHz NMR spectroscopy (¹H) Was analyzed for purity. Elemental analysis is also available from Desert Analytics (Tucson, Ariz.) Was performed using Galbraith Laboratories (Knoxville, TN). High resolution Quantitative spectra (HRMS) were recorded on a Finnegan MAT90. HPLC Using 0.1% TFA as mobile phase, water / acetonitrile (50: 50) with a C18 reverse layer column. BrCN is from Aldrich Chemical Co. Obtained from and used as is. All starting amines are obtained from commercial sources. Prior to use, purify using standard procedures or, if instructed, publish. It was prepared by the following procedure. Chlorobenzene is CaH₂Freshly distilled from Ald An anhydrous high-grade solvent (Sure Seal) supplied by rich was used. Ether (Et₂ O) and tetrahydrofuran before use in sodium / benzophenone ketone Reflux on chill and freshly distill under nitrogen or use anhydrous high-purity supplied by Aldrich. A grade solvent (Sure Seal) was used. All other solvents were reagent grade. Alkyl And arylcyanamide as described above and with BrCN in ether. Published methods by reaction with amines (eg PCT / US92 / 010 50). Example 1: N- (5-acenaphthyl) -N '-(2,3,4-trichlorophenyl) ) Synthesis of guanidine / HCl (method-A (Scheme 1))Step 1.5-acenaphthyl cyanamide   5-amino in a mixture of ether (100 ml) and ethyl acetate (25 ml). Acenaphthene (7.0 g, 41.4 mmol) was dissolved. To this solution, acetonite 5.2 ml of a 5M solution of cyanogen bromide in ril (25.6 mmol of cyanogen bromide) were added. Dissolution The liquid was stirred overnight and a gray precipitate gradually appeared. Solid (of 5-aminoacenaphthene The hydrobromide salt) was removed by filtration and the filtrate was concentrated in vacuo to give a semi-solid residue. A to residue Tell (60 ml) was added and the mixture was stirred overnight. Solid (more 5-amino (Senaphthene hydrobromide) was removed, the filtrate was concentrated to about 20 ml, and then warmed. Dilute with hexane (15 ml). If left at room temperature, off-white crystals will precipitate. Was. It is collected, washed with cyclohexane-ether (1: 1) and vacuum dried To give 1.5 g of pure product. mp 163-65 ° CStep 2. N- (5-acenaphthyl) -N '-(2,3,4-trichlorophenyl ) Guanidine / HCl Synthesis of   5-acenaphthyl cyanamide (0.194 g, 1 mmol) and 2,3,4-to Lichloroaniline hydrochloride (0.221 g, 0.95 mmol; 2,3,4-trichloro A mixture of roaniline and 1.0 N HCl-ether) was added to chlorobenzene. Heat to reflux in 5 ml Zen. All solids dissolve immediately after reaching the reflux temperature And a clear solution was obtained. After refluxing for a total of 2 hours, the mixture is cooled to 20 ° C. and at 24 hours Left for a while. The solid is collected by filtration, washed with excess methylene chloride and at 40 ° C. Vacuum dried to give the product (0.293 g, 68%) as an off-white solid. mp: 208-10 ℃;¹H NMR (CD_ThreeOD): δ7.70-7.58 (m, 3H, Ar-H), 7.48 (d, 2H, J = 7.5Hz, Ar -H), 3.47-3.41 (m, 4H, 2 x CH₂); HRMS: 389.0220 (calculated value: C₁₉H₁₄N_ThreeCl_ThreeAs 389 .0253); Analysis result (C₁₉H_FifteenN_ThreeCl_FourCalculated (as (427.15)): C, 53.42; H, 3.54; N, 9. 84; Cl, 33.2; Found: C, 53.25; H, 3.57; N, 9.67; Cl, 33.75. Example 2: N, N'-bis (5-acenaphthyl) -N-methylguanidine.HC Manufacturing method of 1 (method-B (formula 2))Step 1. Synthesis of N-methyl-N-5-acenaphthyl cyanamide   A suspension of sodium hydride (0.6g, 15.1mmol) in THF (8ml) was added. With stirring, 5-acenaphthyl cyanamide (1.5 g, 7) in THF (22 ml). . Solution (73 mmol) was added slowly at room temperature. After refluxing for 3 hours, the reaction mixture was stirred for 2 hours. Cool to 0 ° C., add methyl iodide (2.64 g, 18.6 mmol) and add 2 contents. Stirred at 0 ° C. After 16 hours, carefully add methanol (15 ml) then water. The reaction was quenched by. salt Extract with methylene chloride (3 x 30 ml), MgSO_FourDried on and solvent Was evaporated. The residue was purified by flash chromatography, a tan solid As a product (0.8 g, 50%) was obtained. TLC (CHCl_Three: CH_ThreeOH ； 10: 1): R_f= 0.72Step 2. N, N'-bis (5-acenaphthyl) -N-methylguanidine.HCl Synthesis of   N-5-acenaphthyl-N-methylcyanami in chlorobenzene (5.8 ml) While stirring a solution of sodium chloride (0.4 g, 1.92 mmol), aluminum chloride (0.9. 28 g, 2.11 mmol) was added at 145 ° C. 10 minutes later, 5-acenaphthenami Hydrochloride (0.39 g, 1.29 mmol, 5-acenaphthene and 1.0 M HCl) -Prepared from ether) was added and reflux continued. After 20 hours, evaporate the reaction mixture The product was purified by flash chromatography to give an amber white solid. This gave the title compound (0.41 g, 55%). mp: 236 ℃; TLC (CH₂Cl₂: CH_ThreeOH; 9: 1); R_f= 0.19;¹H NMR (CDCl_Three+ CD_ThreeOD): δ7.61-7.0 4 (m, 10H, Ar-H), 3.84-3.81 (m, 2H, CH₂) 、 3.43-3.27 (m, 9H, 3 × CH₂And CH_Three); HRM S: 377.1897 (calculated value: C₂₆H_{twenty three}N_ThreeAs 377.1892). Example 3: N, N'-bis (5-acenaphthyl) -N, N'-dimethylguanidi Synthesis of HCl / HCl (Method C (Scheme 2))Step 1. Synthesis of N-methyl-N-5-acenaphthyl cyanamide   Synthesized as described in Example 2, Method B, Step 1.Step 2. Synthesis of N-methyl-N-5-acenaphthylamine   5-acenaphthenamine (5.8 g, 3 in warmed formic acid (97%, 25 ml)) (4.3 mmol) was dissolved and refluxed. After 7 hours, the reaction mixture was cooled to 25 ° C., I left it in the refrigerator for 12 hours. The solid is filtered and Wash with cetonitrile, then air dry to obtain formamide (6.65 g), This was used in the next step without further purification.   A suspension of the above formamide (6.07 g, 30.4 mmol) in THF (100 ml) was added. While stirring the suspension, BH_Three-THF solution (50 ml) was added dropwise at ice bath temperature. Inside After stirring the contents at 25 ° C. for 18 hours, the reaction mixture was concentrated to a volume of about 35 ml, Ethyl (10 ml) was added at 10 ° C. The mixture is quenched with 3N HCl solution, then Basified with NaOH solution. Extract with methylene chloride (2 x 75 ml), dry (Na₂SO_Four), Evaporated to give a tan solid (5.45 g). Methanol The crystals were recrystallized from the above to give the title compound (2.85 g) as yellowish brown crystals. mp 102 ~ 03 ℃Step 3. N, N'-bis (5-acenaphthyl) -N, N'-dimethylguanidine ・ Synthesis of HCl   N-5-acenaphthyl-N-methylcyanamide (in chlorobenzene (7 ml) While stirring a solution of 0.3 g, 1.44 mmol, aluminum chloride (0.21 g , 1.58 mmol) was added at 145 ° C. After 10 minutes, 5-acenaphthene-N-meth Ruamine hydrochloride (0.29 g, 1.3 mmol, 5-acenaphthene-N-methylamido) And 1.0M HCl-ether) and reflux was continued. 4 hours After that, the reaction mixture was evaporated on a rotary evaporator and the product was flash chromatographed. Purify by chromatography and title compound (0.25g, 45%) as a yellow solid. As obtained. mp: 272 ℃; TLC (CH_ThreeCl_Three: CH_ThreeOH; 10: 1); R_f= 0.17;¹H NMR (CD_ThreeOD): δ7.18 (bs, 5H, A r-H), 6.78-6.73 (m, 5H, Ar-H), 3.47 (s, 6H, 2 × CH_Three), 3.24-3.19 (m, 4H, 2 x CH₂), 3 .04 (bs, 4H, 2 × CH₂); HRMS: 391.2051 (calculated: C₂₇H_{twenty five}N_ThreeAs 391.2048).Examples 4-63   By the methods set forth above, including methods AC of each of Examples 1-3, and The following compounds were prepared by using appropriately replaced reagents, These had the indicated physical properties. Example 4: N- (5-acenaphthyl) -N '-(1-anthracenyl) guanidi Mesylate   Synthesis: By Method A of Example 1. White solid; mp: 243-45 ° C;¹H NMR (CD_ThreeOD): δ8 .65-7.25 (m, 14H, Ar-H), 3.33-3.20 (m, 4H, 2 × CH₂), 2.25 (s, 3H, -CH_Three);result of analysis( C₂₈H_{twenty five}N_Three・ CH_ThreeSO_ThreeCalculated: C, 69.54; H, 5.21; N, 8.69; Found: C, 69.33; H, 5.23; N, 8.55. Example 5: N- (5-acenaphthyl) -N '-(4-tert-butylphenyl) g Anidine / HCl   Synthesis: By Method A of Example 1. White solid; TLC (CH₂Cl₂: CH_ThreeOH = 9: 1): R_f= 0.5;  ¹H NMR (CD_ThreeOD): δ 7.65-7.20 (m, 9H, Ar-H), 3.30 (m, 4H, 2 × CH₂), 1.22 (s, 9H, 3 × CH_Three); HRMS: 343.2043 (C_{twenty three}H_{twenty five}N_ThreeCalculated as 343.2048). Example 6: N- (5-acenaphthyl) -N '-(4-cyclohexylphenyl) Guanidine / HCl   Synthesis: 4-Cyclohexylphenyl cyanamide to 5-acenaphthyl-1-ami According to Method A of Example 1 except that the reaction was carried out with hydrochloric acid hydrochloride. White solid: mp: 232-34 ° C;¹H NMR (DMSO): δ7.8-8.2 (m, 13H, Ar-H), 3.4-3.3 (m, 5H, 2xCH₂And CH), 1.8-1.15 (m, 10H, 5 × CH₂); Analysis result (C_{twenty five}H₂₈ClN_ThreeCalculated (as (405.95)): C, 73.9 6; H, 6.95; N, 10.35; Cl, 8.73; Found: C, 73.91; H, 6.96; N, 10.12; Cl, 8.56. Example 7: N- (5-acenaphthyl) -N '-(4-sec-butylphenyl) g Anidine / HCl   Synthesis: By Method A of Example 1. White solid; TLC (CH₂Cl₂: CH_ThreeOH = 9: 1): R_f= 0.7; 1H NMR (CD_ThreeOD): δ 7.60-7.15 (m, 9H, Ar-H), 3.30 (m, 4H, 2 × CH₂) ， 2.52 (q , 1H, -CH), 1.50 (m, 2H, -CH₂) ， 1.11 (d, 3H, CH_Three) ， 0.71 (t, 3H, CH_Three); HRMS: 343.2051 (C_{twenty three}H_{twenty five}N_ThreeCalculated as 343.2049). Example 8: N- (5-acenaphthyl) -N '-(4-methoxyphenyl) guani Jin HBr   Synthesis: By Method A of Example 1. Fluffy creamy solid; mp: 187-200 ℃ ; TLC (CHCl_Three: CH_ThreeOH = 10: 1): R_f= 0.31;¹H NMR (CDCl_Three): δ7.45-7.10 (m, 7H, Ar-H), 6.80 (d, 2H, J: 8Hz, Ar-H), 3.68 (s, 3H, OCH_Three), 3.38-3.22 (m, 4H, 2 × CH₂); HRMS: 3 17.1509 (calculated value: C₂₀H₁₉N_Three317.1528 as O); analysis result (C₂₀H₂₀N_ThreeBrO (398.30) Calculated: C, 60.44; H, 5.08; N, 10.58; Found: C, 60.28; H, 5.14; N, 10.41. Example 9: N- (5-acenaphthyl) -N '-(2,3-dichlorophenyl) g Anidine / HCl   Synthesis: By Method A of Example 1. Yellowish white solid; mp: 124-30 ℃; TLC (C HCl_Three: CH_ThreeOH = 10: 1): R_f= 0.18;¹H NMR (CDCl_Three): δ7.59 (d, 1H, J = 8Hz, Ar-H), 7.47 (t , 1H, J = 8Hz, Ar-H), 7.36-7.14 (m, 6H, Ar-H), 3.40-3.25 (m, 4H 2 × CH₂); HRMS: 355. 0647 (C₁₉H_FifteenC₁₂N_ThreeCalculated as 355.0643). Example 10: N- (5-acenaphthyl) -N '-(4-methoxy-2-naphthyl) ) Guanidine   Synthesis: By Method A of Example 1. Pale yellow solid; mp: 191-92 ℃; TLC (CH₂Cl₂: CH_ThreeO H = 9: 1): R_f= 0.51;¹H NMR (CD_ThreeOD + CDCl_Three): δ8.17 (d, 1H, J = 8Hz, Ar-H), 7.73 (d, 1H , J = 8Hz, Ar-H), 7.66 (d, 1H, J = 8Hz, Ar-H), 7.57-7.26 (m, 7H, Ar-H), 7.09 (d, 1H, J = 8 Hz, Ar-H), 3.96 (s, 3H, OCH_Three), 3.43-3.35 (m, 4H, 2 x CH₂); HRMS: 367.1680 (C_{twenty four}H_{twenty one} ON_ThreeCalculated as 367.1685). Example 11: N- (5-acenaphthyl) -N '-(3,4-dichlorophenyl) Guanidine / HCl   Synthesis: By Method A of Example 1. White solid; mp:> 300 ℃; TLC (CHCl_Three: CH_ThreeOH: 10 : 1): R_f= 0.27;¹H NMR (CDCl_Three): δ7.55 (d, 1H, J = 8Hz, Ar-H), 7.48 (t, 1H, J = 8Hz, Ar-H ), 7.37 (d, 2H, J = 8Hz, Ar-H), 7.30 (t, 2H, J = 8Hz, Ar-H), 7.19 (d, 1H, J = 7Hz, Ar-H), 7.13 (bd, 1H, Ar-H), 3.66-3.30 (m, 4H, 2 × CH₂); HRMS: 355.0651 (C₁₉H_FifteenCl₂N_Threeage Calculated value is 355.0643). Example 12: N- (5-acenaphthyl) -N '-(4-chlorophenyl) guani Jin HBr   Synthesis: N-4-chlorophenyl cyanamide odor of 5-acenaphthyl-1-amine According to Method A of Example 1 except reacted with the hydrohalide salt. White solid; mp: 216-1 7 ° C;¹H NMR (CDCl_Three): δ7.65-7.23 (m, 9H, Ar-H), 3.42-3.35 (m, 4H, 2 × CH₂);¹³C N MR (CDCl_Three): 147.81, 146.47, 140.09, 133.35, 132.11, 131.98, 129.90, 129.40 , 127.48, 126.83, 126.70, 126.66, 124.65, 124.51, 120.52, 118.95, 30.49 ， 29.94; HRMS: 321.1039 (C₁₉H₁₆N_ThreeCalculated value as Cl 321.1033). Example 13: N- (5-acenaphthyl) -N '-(2-naphthyl) guanidine. HCl   Synthesis: By Method A of Example 1. Pale yellow solid; mp: 200 ℃; TLC (CHCl_Three: CH_ThreeOH = 10 : 1): R_f= 0.14;¹H NMR (CDCl_Three+ CD_ThreeOD): δ7.78-7.14 (m, 12H, Ar-H), 3.33-3.25 (m, 4 H, 2 x CH₂); HRMS: 337.1500 (C_{twenty three}H₁₉N_ThreeCalculated as 337.1579). Example 14: N- (5-acenaphthyl) -N '-(6-quinolinyl) guanidine ・ HCl   Synthesis: By Method A of Example 1. White solid; mp: 242-44 ℃; TLC (CHCl_Three: MeOH = 10: 1): R_f= 0.2;¹H NMR (DMSO): δ9.1-7.3 (m, 11H, Ar-H), 3.5-3.2 (m, 4H, 2 × CH₂). Example 15: N- (5-acenaphthyl) -N '-(4-nitrophenyl) guani Gin / HCl   Synthesis: By Method A of Example 1. Off-white solid; mp: 85-86 ℃;¹H NMR (CD_ThreeOD): δ 7.57-7.05 (m, 9H, Ar-H), 3.49-3.43 (m, 4H, 2 × CH₂); MS (C1): m / e 333 (M⁺¹: Free salt Group). Example 16: N- (5-acenaphthyl) -N '-(3-biphenyl) guanidine ・ HCl   Synthesis: By Method A of Example 1. White cream solid; mp: 128-36 ℃; TLC (CHC l_Three: CH_ThreeOH = 10: 1): R_f= 0.56;¹H NMR (CD_ThreeOD): δ 7.68-7.35 (m, 14H, Ar-H), 3.45-3.3 1 (m, 4H, 2 × CH₂); HRMS: 363.1726 (C_{twenty five}H_{twenty one}N_ThreeCalculated as 363.1735). Example 17: N- (5-acenaphthyl) -N '-(2,3-dimethylphenyl) Guanidine / HCl   Synthesis: By Method A of Example 1. Pale yellow solid; mp: 199-207 ℃; TLC (CHCl_Three: CH_ThreeO H = 10: 1): R_f= 0.38;¹H NMR (CD_ThreeOD): δ7.68-7.58 (m, 2H, Ar-H), 7.48 (d, 1H, J = 8Hz , Ar-H), 7.41-7.36 (m, 2H, Ar-H), 7.23-7.16 (m, 3H, Ar-H), 3.45-3.39 (m, 4H, 2 × C H₂), 2.34 (s, 3H, CH_Three), 2.28 (s, 3H, CH_Three); HRMS: 315.1717 (C_{twenty one}H_{twenty one}N_ThreeCalculated as 3 15.1735). Example 18: N- (5-acenaphthyl) -N '-(2-biphenyl) guanidine ・ HBr   Synthesis: By Method A of Example 1. White solid; mp: 141-43 ° C;¹H NMR (CD3OD): δ7 .56-7.05 (m, 14H, Ar-H), 3.43-3.31 (m, 4H, 2 × CH₂); MS (E1): m / e 364 (M⁺¹: Free salt ); HRMS: 363.1737 (C_{twenty five}H_{twenty one}N_ThreeCalculated as 363.1735). Example 19: N- (5-acenaphthyl) -N '-(2,5-dibromophenyl) Guanidine / HCl   Synthesis: By Method A of Example 1. Yellowish solid; mp: 194-96 ℃; TLC (CHCl_Three : CH_ThreeOH = 9: 1): R_f= 0.33;¹H NMR (CD_ThreeOD): δ7.74-7.34 (m, 8H, Ar-H), 3.50-3.42 (m , 4H, 2 × CH₂); HRMS: 442.9678 (C₁₉H_FifteenBr₂N_ThreeCalculated as 442.9633). Example 20: N- (acenaphthyl) -N '-(3,4-dimethoxyphenyl) g Anidine / HCl   Synthesis: By Method A of Example 1. Brown solid; mp: 152-55 ℃; TLC (CHCl_Three: CH_ThreeOH = 1 0: 1): R_f= 0.27;¹H NMR (CD_ThreeOD): δ7.70-7.58 (m, 2H, Ar-H), 7.47 (d, 1H, J = Hz, Ar-H ), 7.41-7.35 (m, 2H, Ar-H), 7.04-6.92 (m, 3H, Ar-H), 3.85 (s, 3H, CH_Three), 3.84 (s, 3H , CH_Three), 3.47-3.44 (m, 2H, 2 × CH_Three); HRMS: 347.1637 (C_{twenty one}H_{twenty one}O₂N_ThreeCalculated as 347.1 634). Example 21: N- (5-acenaphthyl) -N '-(4-methoxy-1-naphthyl) ) -N-Methylguanidine.HCl   Synthesis: By Method B of Example 2. Pale yellow solid; mp: 158-59 ℃; TLC (CHCl_Three: CH_ThreeOH = 10: 1): R_f= 0.25;¹H NMR (CD_ThreeOD): δ8.30-6.90 (m, 11H, Ar-H), 4.03 (s, 3H, OCH_Three) ， 3.64 (bs, 3H, N-CH_Three), 3.50-3.41 (m, 4H, 2 x CH₂); HRMS: 381.1850 (C_{twenty five}H_{twenty three}ON_ThreeWhen Then calculated value 381.1841). Example 22: N- (5-acenaphthyl) -N '-(4-methoxy-1-naphthyl) ) -N′-Methylguanidine · HCl   Synthesis: N-methyl-N- (4-methoxy-1-naphthyl) cyanamide 5-A By Method B of Example 2 except reacted with senaftyl-1-amine hydrochloride. White solid; mp: 195-97 ℃; TLC (CHCl_Three: CH_ThreeOH = 10: 1): R_f= 0.10;¹H NMR (CD_ThreeOD): δ8.37 (d, 1H, J = 8.4Hz, Ar-H), 7.95-7.28 (m, 9H, Ar-H), 7.05 (d, 1H, J = 8.3Hz, Ar-H), 4,07 (s, 3H, OCH_Three) ， 3.60 (bs, 3H, N-CH_Three), 3.47-3.31 (m, 4H, 2 x CH₂); HRMS: 381.1840 (C_{twenty five}H_{twenty three}ON_ThreeCalculated as 381.1841). Example 23: N- (5-acenaphthyl) -N '-(4-methoxy-1-naphthyl) ) -N, N'-Dimethylguanidine.HCl   Synthesis: By Method C of Example 3. White solid; mp: 210-12 ℃; TLC (CHCl_Three: CH_ThreeOH: 1 0: 1): R_f= 0.34;¹H NMR (CD_ThreeOD): δ7.95 (d, 1H, Ar-H), 7.38-6.65 (m, 10H, Ar-H), 3 .82 (s, 3H, OCH_Three), 3.48 (s, 3H, N-CH_Three) ， 3.42 (s, 3H, N-CH_Three), 3.25-3.18 (m, 2H, CH₂), 3.04-2.65 (m, 2H, CH₂); HRMS: 395.2005 (C₂₆H_{twenty five}ON_ThreeCalculated as 395.1998). Example 24: N- (5-acenaphthyl) -N '-(4-chloro-1-naphthyl) Guanidine / HCl   Synthesis: By Method A of Example 1. White solid; mp: 258-60 ° C;¹H NMR (CD_ThreeOD): δ8 .38-8.35 (m, 1H, Ar-H), 8.15-8.11 (m, 1H, Ar-H), 7.81-7.34 (m, 9H, Ar-H), 3.44-3. 41 (m, 4H, 2 × CH₂); MS (E1): m / e 372 (M⁺¹: Free base; analysis result (C_{twenty three}H₁₉Cl₂N_Three(408. 31)) Calculated: C, 57.65; H, 4.69; N, 10.29; Found: C, 67.58; H, 4.60; N, 10 .28; HPLC (CH in 0.1% TFA, CH_ThreeCN: H₂O = 50: 50): Purity 99.9%. Example 25: N- (5-acenaphthyl) -N '-(3,4,5-trichlorophene Nil) guanidine / HCl   Synthesis: By Method A of Example 1. White solid; mp: 234-36 ℃; TLC (CH₂Cl₂: CH_ThreeOH = 9: 1): R_f= 0.28;¹H NMR (CD_ThreeOD): δ 7.68-7.35 (m, 7H, Ar-H), 3.53-3.40 (m, 4H, 2 × C H₂); HRMS: 381.0251 (C₁₉H₁₄Cl_ThreeN_ThreeCalculated as 389.0253); HPLC (0.1% in TFA, CH_Three CN: H₂O = 50: 50): Purity 95.5%. Example 26: N- (5-acenaphthyl) -N '-(4-biphenyl) guanidine ・ CH_ThreeSO_ThreeH   Synthesis: By Method A of Example 1. White solid; mp: 196-98 ℃; TLC (CHCl_Three: CH_ThreeOH: 1 0: 1): R_f= 0.29;¹H NMR (CD_ThreeOD): δ7.75-7.36 (m, 14H, Ar-H), 3.45 (bs, 4H, 2 × CH₂) ， 2.69 (s, 3H, CH_Three); HRMS: 363.1737 (C_{twenty five}H_{twenty one}N_ThreeCalculated as 363.1735). Example 27: N- (5-acenaphthyl) -N '-(2,3,4,5-tetrachloro Rophenyl) guanidine / HCl   Synthesis: By Method A of Example 1. White solid: mp: 223-25 ℃; TLC (CH₂Cl₂: CH₂OH = 9: 1); R_f= 0.51;¹H NMR (CD_ThreeOD): δ7.74-7.33 (m, 6H, Ar-H), 3.47-3.40 (m, 4H, 2 × C H₂); Analysis result (C₁₉H₁₃Cl_FourN_ThreeCalculated (as (461.59)): C, 49.44; H, 3.06; N, 9.1; Found: C, 50.89; H, 3.15; N, 8.84; HRMS: 422.9875 (C₁₉H₁₃Cl_FourN_ThreeCalculated as 42 2.9864); HPLC (in 0.1% TFA, CH_ThreeCN: H₂O = 45: 55): Purity 95.5%. Example 28: N- (5-acenaphthyl) -N '-(3-isopropylphenyl) Guanidine / HCl   Synthesis: By Method A of Example 1. White solid; mp: 149-51 ℃; TLC (CHCl_Three: CH_ThreeOH = 1 0: 1); R_f= 0.28;¹HNMR (CD_ThreeOD): δ7.66-7.19 (m, 9H, Ar-H), 3.44 (bs, 4H, 2 × CH₂), 3.00-2.89 (m, 1H, -CH-), 1.26 (d, 6H, J = 7Hz, 2 × CH_Three); HRMS: 329.1873 (C_{twenty three}H_{twenty five}N_ThreeWhen Then calculated value 329.1892). Example 29: N- (5-acenaphthyl) -N '-(3-tert-butylphenyl) Guanidine / HCl   Synthesis: By Method A of Example 1. White solid; mp: 176-78 ℃; TLC (CHCl_Three: CH_ThreeOH = 1 0: 1): R_f= 0.26;¹H NMR (CD_ThreeOD): δ 7.68-7.28 (m, 9H, Ar-H), 3.45-3.44 (m, 4H, 2 × C H₂) ， 1.33 (s, 3H, CH_Three); HRMS: 343.2055 (C_{twenty two}H_{twenty three}N_ThreeAs Calculated value 343.2048). Example 30: N- (5-acenaphthyl) -N '-(2,3,5,6-tetrachloro Rophenyl) guanidine / CH_ThreeSO_ThreeH   Synthesis: By Method A of Example 1. White solid; mp: 248-50 ° C;¹H NMR (CD_ThreeOD): δ8 .12-7.33 (m, 6H, Ar-H), 3.44-3.40 (m, 4H, 2 × CH₂), 2.69 (s, 3H, CH_Three); MS (E1): m / e  426 (M⁺¹: Free base). Example 31: N- (5-acenaphthyl) -N '-(3-iodophenyl) guani Gin / HCl   Synthesis: By Method A of Example 1. White solid: mp: 203-04 ℃; TLC (CHCl_Three: CH_ThreeOH = 1 0: 1); R_f= 0.19;¹H NMR (CD_ThreeOD): δ7.76-7.58 (m, 4H, Ar-H), 7.47 (d, 1H, J = 7.33Hz, Ar-H), 7.42-7.34 (m, 3H, Ar-H), 7.22 (t, 1H, J = 8Hz, Ar-H), 3.45-3.44 (m, 4H, 2 × CH₂ ); HRMS: 413.0395 (C₁₉H₁₆IN_ThreeCalculated as 413.0389). Example 32: N- (5-acenaphthyl) -N '-(3-nitrophenyl) guani Gin / HCl   Synthesis: By Method A of Example 1. Yellow solid; mp: 244-48 ℃; TLC (CHCl_Three: CH_ThreeOH = 1 0: 1); R_f= 0.16;¹H NMR (CD_ThreeOD): δ8.25-8.16 (m, 2H, Ar-H), 7.80-7.58 (m, 4H, Ar-H ), 7.51 (d, 1H, J = 7.24Hz, Ar-H), 7.41 (d, 1H, J = 6.9Hz, Ar-H), 7.37 (d, 1H, J = 7.4Hz, Ar-H); HRMS: 332.1276 (C₁₉H₁₆N_FourO₂Calculated as 332.1273). Example 33: N- (5-acenaphthyl) -N '-(5-indolinyl) guanidi HCl   Synthesis: By Method A of Example 1. Yellowish white solid; mp: 147-48 ℃; TLC (CHCl_Three: CH_ThreeOH : 10: 1); R_f: 0.27;¹H NMR (CD_ThreeOD): δ7.65-7.57 (m, 2H, Ar-H), 7.46 (d, 1H, J = 7.3H z, Ar-H), 7.41-7.29 (m, 3H, Ar-H), 7.22 (bs, 1H, Ar-H), 7.12 (dd, 1H, J = 7.9 and 2.1Hz, Ar-H), 3.47-3.43 (m, 4H, 2 × CH₂), 2.92 (dd, 4H, J = 14.8 and 7.4Hz, 2 × Ar-CH₂), 2.10 (m, 2H, CH₂); HRMS: 327.1742 (C_{twenty two} H_{twenty one}N_ThreeCalculated as 327.1735). Example 34: N- (5-acenaphthyl) -N '-(3-acenaphthyl) guanidi CH_ThreeSO_ThreeH   Synthesis: By Method A of Example 1. White solid; mp: 245 ° C;¹H NMR (300MHz, CD_ThreeOD) : δ 7.69-7.73 (m, 2H, Ar-H), 7.60-7.65 (m, 2H, Ar-H), 7.49-7.53 (m, 2H, Ar-H), 7. 35-7.48 (m, 4H, Ar-H), 3.41-3.49 (m, 4H, 2 × CH₂), 2.68 (s, 3H, CH_Three); MS (E1): m / e 363 (M⁺: Free base); C_{twenty five}H_{twenty one}N_Three・ CH_ThreeSO_ThreeH / 2H₂Elemental analysis of O: Calculated: C, 61.62; H, 5.76; N, 8.28; S, 6.32; Found: C, 61.77; H, 5.43; N, 8.22; S, 5.47; HPLC (AcCN: H₂O = 1: 1): Purity 99.3%. Example 35: N- (5-acenaphthyl) -N '-(2-fluorenyl) guanidi HCl   Synthesis: By Method A of Example 1. Pale yellowish white solid; mp: 239-240 ℃;¹H NMR (300MH z, CD_ThreeOD): δ7.90-7.92 (d, 1H, J = 8Hz, Ar-H), 7.82-7.84 (d, 1H, J = 7Hz, Ar-H), 7.69 -7.72 (d, 1H, J = 8Hz, Ar-H), 7.62-7.64 (m, 3H, Ar-H), 7.48-7.51 (d, 1H, J = 7.5Hz, Ar- H), 7.29-7.41 (m, 5H, Ar-H), 3.95 (s, 2H, CH₂) 、 3.40-3.47 (m, 4H, 2-CH₂); MS (E1):  m / e 375 (M⁺: Free base); C₂₆H_{twenty one}N_Three・ HCl ・ O ・ 25H₂Elemental analysis of O: Calcd: C, 74.99;  H, 5.44; N, 10.08; Found: C, 75.25; H, 5.44; N, 10.14. Example 36: N- (5-acenaphthyl) -N '-(4-n-butoxyphenyl) Guanidine / HCl   Synthesis: By Method A of Example 1. Brownish solid; mp: 90 ° C;¹H NMR (300MHz , CD_ThreeOD): δ7.57-7.67 (m, 2H, Ar-H), 7.45-7.47 (d, 1H, J = 7.5Hz, Ar-H), 7.34-7.40 (m, 2Hm, Ar-H), 7.27-7.30 (m, 2H, Ar-H), 6.99-7.02 (m, 2H, Ar-H), 3.97-4.02 (t, 2H, OCH₂) 、 3.41-3.47 (m, 4H, 2-CH₂), 1.71-1.78 (dt, 2H, C H₂), 1.46-1.54 (m, 2H, CH₂) ， 0.95-1.00 (t, 3H, CH_Three); MS (E1): m / e359 (M⁺: Free salt Group); elemental analysis (C_{twenty three}H_{twenty five}N_ThreeO ・ HCl ・ O ・ 75H₂As O): Calculated: C, 67.47; H, 6.77; N, 10.26; Found: C, 67.66; H, 6.67; N, 10.26. Example 37: N- (5-acenaphthyl) -N '-(3- (2-methoxy) diben Zofuranyl) guanidine / HCl   Synthesis: By Method A of Example 1. White solid; mp: 230 ° C;¹H NMR (300MHz, CD_ThreeOD) : Δ8.06-8.09 (dd, 1H, J1 = 7.5Hz, J2 = 1.5Hz, Ar-H), 7.80 (s, 1H, Ar-H), 7.73-7.76 (d, 1H, J = 7.5Hz, Ar-H), 7.60-7.65 (m, 3H, Ar-H), 7.46-7.56 (m, 2H, Ar-H), 7.34-7. 40 (m, 3H, Ar-H), 4.10 (s, 3H, O-CH_Three), 3.40-3.43 (m, 4H, 2-CH₂); MS (E1): m / e 407 ( M⁺: Free base); Elemental analysis (C₂₆H_{twenty one}N_ThreeO₂・ HCl ・ O ・ 25H₂As O): Calculated: C, 69.64 H, 5.06; N, 9.36; Found: C, 69.68; H, 4.98; N, 9.40. Example 38: N- (5-acenaphthyl) -N '-(9-hydroxy-2-fluor Renyl) guanidine / HCl   Synthesis: By Method A of Example 1. White solid; mp: 265 ° C;¹H NMR (300MHz, CD_ThreeOD) : δ7.80-7.83 (d, 1H, J = 8Hz, Ar-H), 7.69-7.74 (t, 2H, Ar-H), 7.60-7.64 (m, 3H, Ar- H), 7.49-7.52 (d, 1H, J = 7.5Hz, Ar-H), 7.34-7.42 (m, 5H, Ar-H), 5.58 (s, 1H, -OH), 3.45 (brs, 4H, 2-CH₂); MS (E1): m / e 391 (M⁺: Free base); Elemental analysis (C₂₆H_{twenty one}N_ThreeO ・ HCl ・ O ・ 25H₂As O): Calculated: C, 72.22; H, 5.24; N, 9.7; Found: C, 72.35; H, 5.35; N, 9.58. Example 39: N- (5-acenaphthyl) -N '-(4-trifluoromethylphene Nil) guanidine / HCl   Synthesis: By Method A of Example 1. White solid; mp: 234-236 ℃; TLC (CH₂Cl₂: CH_ThreeOH = 9: 1): R_f= 0.4;¹H NMR (CDC_l3): 7.70-7.25 (m, 9H, Ar-H), 3.46 -3.38 (m, 4H, 2 × CH₂); MS (C1): m / e 356 (M⁺¹); Analysis result (C₂₀H₁₆N_ThreeF_Three・ HCl (391.82 ))): Calculated: C, 61.31; H, 4.37; N, 10.72; Found: C, 62.14; H, 4.34; N, 10 .80. Example 40: N- (5-acenaphthyl) -N '-(4-methylthiophenyl) g Anidine / HCl   Synthesis: By Method A of Example 1. White solid; mp: 168-170 ℃; TLC (CH₂Cl₂: CH_ThreeOH = 9: 1): R_f= 0.38;¹H NMR (CD_ThreeOD): 7.76-7.38 (m, 9H, Ar-H), 3.53-3.37 (m, 4H, 2 ×- CH₂), 2.57 (s, 3H, -SCH_Three); MS (C1): m / e 334 (M⁺¹); Analysis result (C₂₀H₁₉N_ThreeS-HCl (369. 91)): Calculated: C, 64.94; H, 5.45; N, 11.36; Found: C, 64.38; H, 5.73; N, 11.05. Example 41: N- (5-acenaphthyl) -N '-(4-benzyloxyphenyl) ) Guanidine / HCl Light green foam; mp: 117-127 ℃; TLC (CH₂Cl₂: CH_ThreeOH = 15: 1): R_f= 0.50;¹H NMR (C_D3OD) : 7.646-7.094 (m, 14H, Ar-H), 5.127 (s, 2H, CH₂), 3.454-3.449 (m, 4H, CH₂CH₂); Minutes Analysis result (C₂₆H_{twenty three}N_ThreeO.HCl (429.95)): Calculated: C, 72.63; H, 5.63; N, 9.77; actual Measured: C, 72.20; H, 5.70; N, 9.65. Example 42: N- (5-acenaphthyl) -N '-(3-benzyloxyphenyl) ) Guanidine / HCl Light green foam; mp: 94-98 ℃; TLC (CH₂Cl₂: CH_ThreeOH = 15: 1): R_f= 0.50;¹H NMR (CD_ThreeOD): 7.639-6.981 (m, 14H, Ar-H), 5.117 (s, 2H, CH₂) 、 3.451-3.344 (m, 4H, CH₂CH₂);analysis Result (C₂₆H_{twenty three}N_ThreeO ・ HCl ・ 0.5H₂As O (438.95)): Calculated: C, 71.07; H, 5.70; N, 9.57 Found: C, 71.44; H, 5.60; N, 9.83. Example 43: N- (5-acenaphthyl) -N '-(3-benzyloxyphenyl ) Guanidine mesylate Light green foam; mp: 90-98 ℃; TLC (AcOEt: CH_ThreeOH = 10: 1): R_f= 0.30;¹H NMR (CDCl_Three): 7.647-7.268 (m, 11H, Ar-H), 6.956-6.923 (m, 3H, Ar-H), 5.086 (s, 2H, CH₂ ) 、 3.458-3.410 (m, 4H, CH₂CH₂), 2.857 (s, 3H, CH_Three); Analysis result (C₂₇H₂₇N_ThreeO4S (489.59 ))): Calculated: C, 66.24; H, 5.56; N, 8.58; Found: C, 66.99; H, 5.35; N, 8.74 . Example 44: N- (5-acenaphthyl) -N '-(3-sec-butylphenyl) Guanidine mesylate White solid; mp: 136-138 ℃; TLC (CH₂Cl₂: MeOH = 15: 1): R_f= 0.31;¹H NMR (CD_ThreeOD): 7 .668-7.164 (m, 9H, Ar-H), 3.483-3.411 (m, 4H, CH₂CH₂) ， 2.655-2.627 (m, 1H, CH) ， 1 .656-1.589 (m, 2H, CH₂) 、 1.257-1.234 (d, 3H, J = 6.87Hz, CH_Three), 0.860-0.813 (m, 3H, C H_Three); Analysis result (C_{twenty three}H₂₆N_ThreeCl (379.93)): Calculated: C, 72.71; H, 6.90; N, 11.06;  Found: C, 72.73; H, 6.75; N, 11.12. Example 45: N- (5-acenaphthyl) -N '-(2-anthracenyl) guani Gin / HCl Green solid; mp: 260-262 ℃; TLC (CH₂Cl₂: MeOH = 15: 1): R_f= 0.31;¹H NMR (CD_ThreeOD): 8 .527-8.502 (d, 2H, J = 7.63Hz, Ar-H), 8.183-8.153 (d, 1H, J = 9.28Hz, Ar-H), 8.044 (s , br, 3H, Ar-H), 7.771-7.617 (m, 2H, Ar-H), 7.542-7.368 (m, 6H, Ar-H), 3.449-3.41 8 (m, 4H, CH₂CH₂); Analysis result (C₂₇H_{twenty two}N_ThreeCl (423.50)): Calculated: C, 76.50; H, 5.2 3; N, 9.91; Found: C, 76.33; H, 5.46; N, 9.70. Example 46: N- (5-acenaphthyl) -N '-(3-phenethylphenyl) g Anidine / HCl White solid; mp: 116-118 ℃; TLC (CH₂Cl₂: MeOH = 15: 1): R_f= 0.31;¹H NMR (CD_ThreeOD): 7 .645-7.156 (m, 14H, Ar-H), 4.233-4.161 (q, 1H, J = 7.14Hz, CH), 3.478-3.414 (m, 4H, CH₂CH₂), 1.650-1.626 (d, 3H, J = 7.20Hz, CH_Three); Analysis result (C₂₇H₂₆N_ThreeCl (427.98) ): Calculated: C, 75.77; H, 6.12; N, 9.82; measured Values: C, 75.63; H, 5.98; N, 9.69. Example 47: N- (5-acenaphthyl) -N '-(4-adamantylphenyl) Guanidine / HCl White solid; mp: 240 ℃; TLC (CH₂Cl₂: MeOH = 15: 1): R_f= 0.31;¹H NMR (CD_ThreeOD): 7.639 -7.289 (m, 9H, Ar-H), 3.443-3.403 (m, 4H, CH₂CH₂) ， 2.086-1.756 (m, 13H, CH's); min Analysis result (C₂₉H₃₂N_ThreeCl (458.08)): Calculated: C, 76.04; H, 7.04; N, 9.17; Found:  C, 75.97; H, 6.88; N, 9.06. Example 48: N- (5-acenaphthyl) -N '-(3-benzyloxyphenyl) ) -N′-Methylguanidine · HCl White solid; mp: 102-105 ℃; TLC (CH₂Cl₂: MeOH = 15: 1): R_f= 0.30;¹H NMR (CD_ThreeOD): 7 .605-7.134 (m, 14H, Ar-H), 5.149 (s, 2H, CH₂) ， 3.636 (s, 3H, CH_Three), 3.532-3.444 (m, 4H, CH₂CH₂); Analysis result (C₂₇H₂₆N_ThreeClO (443.98)): Calculated: C, 73.04; H, 5.98;  N, 9.46; Found: C, 72.98; H, 5.95; N, 9.42. Example 49: N- (5-acenaphthyl) -N '-(4-benzyloxyphenyl) ) -N′-Methylguanidine · HCl White solid; mp: 108-110 ℃; TLC (CH₂Cl₂: MeOH = 15: 1): R_f= 0.30;¹H NMR (CD_ThreeOD): 7 .605-7.134 (m, 14H, Ar-H), 5.149 (s, 2H, CH₂) ， 3.536 (s, 3H, CH_Three), 3.532-3.444 (m, 4H, CH₂CH₂); Analysis result (C₂₇H₂₆N_ThreeClO (443.98)): Calculated: C, 73.04; H, 5.98;  N, 9.46; Found: C, 72.93; H, 6.00; N, 9.919. Example 50: N- (5-acenaphthyl) -N '-(3-biphenyl) -N'-me Chillguanidine / HCl White solid; mp: 217 ℃; TLC (CH₂Cl₂: MeOH = 10: 1): R_f= 0.30;¹H NMR (CDCl_Three): 7.513 -7.022 (m, 14H, Ar-H), 3.668 (s, 3H, CH_Three) 、 3.322-3.203 (m, 4H, CH₂CH₂); Analysis result (C₂₆H_{twenty four}N_ThreeCl ・ 2H₂As O (449.98)): Calculated: C, 69.40; H, 6.27;  N, 9.34; Found: C, 69.25; H, 6.27; N, 9.48. Example 51: N- (5-acenaphthyl) -N '-(3- (1'-methyl-2'- Phenyl) ethyl) guanidine / HCl White solid; mp: 106-108 ℃; TLC (CH₂Cl₂: MeOH = 15: 1): R_f= 0.36;¹H NMR (CD_Three0D): 7 .698-7.070 (m, 14H, Ar-H), 3.467-3.312 (m, 4H, CH, CH₂CH₂) ， 3.105-3.033 (m, 1H, CH ) ， 2.928-2.810 (m, 2H, CH₂), 1.267-1.244 (d, 3H, J = 6.87Hz, CH_Three); Analysis result (C₂₈H₂₈ N_ThreeCl (442.00)): Calculated: C, 76.09; H, 6.39; N, 9.51; Found: C, 76.11; H, 6 .55; N, 9.38. Example 52: N- (5-acenaphthyl) -N '-(3,4-tetralinylphenyi Le) guanidine / HCl White solid; mp: 158-160 ℃; TLC (CH₂Cl₂: MeOH = 15: 1): R_f= 0.36;¹H NMR (CDCl_Three): 7 .631-6.985 (m, 8H, Ar-H), 3.484-3.373 (m, 4H, CH₂'s), 2.747 (m, 2H, CH₂) ， 1.793-1 .784 (m, 2H, CH₂); Analysis result (C_{twenty three}H_{twenty four}Cl (377.92)): Calculated: C, 73.10; H, 6.40 N, 11.12; Found: C, 72.88; H, 6.25; N, 11.03. Example 53: N- (5-acenaphthyl) -N '-(7-benzyltetralinyl) Guanidine / HCl White solid; mp: 161-162 ° C; TLC (AcOEt: MeOH = 10: 1): R_f= 0.44;¹1 H NMR; 7.647-7.1 18 (m, 13H, Ar-H); Analysis result (C₃₀H₃₀N_ThreeCl / 1 / 2H₂O (477.04)); Calculated: C, 75.4 7; H, 6.50; N, 8.81; Found: C, 75.23; H, 6.28; N, 8.820. Example 54: N- (5-acenaphthyl) -N '-(3,4-dibenzyloxyfuran Phenyl) guanidine mesylate White solid; mp: 185-187 ° C; TLC (AcOEt: MeOH = 10: 1): R_f= 0.44;¹1 H NMR; 7.647-7.118 (m, 13H, Ar-H); Analysis result (C₃₀H₃₀N_ThreeO_FiveS ・ H₂As O (613.73)); Calculated : C, 66.54; H, 5.75; N, 6.85; Found: C, 66.86; H, 5.36; N, 6.92. Example 55: N- (5-acenaphthyl) -N '-(3- (1- (4-ethoxyphenyl) Phenyl) propyl) phenyl) guanidine mesylate White solid; mp: 93-95 ° C .; TLC (AcOEt: MeOH = 10: 1): R_f= 0.049;¹1 H NMR; 7.636-7.57 5 (m, 2H, Ar-H), 7.416-7.128 (m, 11H, Ar-H), 6.922 (s, 1H, Ar-H), 6.871-6.842 (d, 2 H, J = 8.72Hz, Ar-H), 6.639-6.610 (d, 2H, J = 8.66Hz, Ar-H), 3.782-3.748 (q, 2H, J = 7. 40Hz, OCH₂) 、 3.498-3.417 (m, 4H, CH₂CH₂), 3.006-2.980 (m, 1H, CH), 2.848 (s, 3H, C) H_Three) ， 2.835-2.706 (m, 2H, CH₂) 、 1.317-1.193 (m, 6H, CH_Three, CH_Three); Analysis result (C₃₁H₃₅N_Three O_FourAs S (545.70)): Calculated: C, 68.23; H, 6.46; N, 7.70; Found: C, 68.30; H, 6. 44; N, 7.85. Example 56: N- (5-acenaphthyl) -N '-(3- (N ", N" -dibenzyl Luamino) phenyl) guanidine mesylate White solid; mp: 150-152 ° C; TLC (AcOEt: MeOH = 10: 1): R_f= 0.44;¹1 H NMR; 7.568-7.1 74 (m, 17H, Ar-H), 6.745-6.530 (m, 2H, Ar-H), 4.697 (s, 2H, CH₂) ， 3.497-3.413 (m, 4 H, CH₂CH₂) ， 2.825 (s, 3H, CH_Three); HRMS: 482.2446 (C₃₃H₃₀N_FourCalculated as 482.628). Example 57: N- (5-acenaphthyl) -N '-(3- (1'-benzylbutyl) ) Phenyl) guanidine mesylate White solid; mp: 90-92 ° C; TLC (AcOEt: MeOH = 10: 1): R_f= 0.48;¹H NMR (CDCl_Three): 7.65 5-7.558 (m, 2H, Ar-H), 7.411-7.269 (m, 5H, Ar-H), 7.169-6.800 (m, 7H, Ar-H), 3.49 2-3.414 (m, 4H, CH₂CH₂) ， 3.022-2.662 (m, 3H, CH₂, CH) 2.842 (s, 3H, CH_Three), 1.733-1. 695 (m, 2H, CH₂) 、 1.252-1.176 (m, 2H, CH₂), 0.895-0.847 (t, J = 7.28Hz, CH_Three); HRMS: 433.2516 (C₃₀H₃₁N_ThreeCalculated as 433.5962). Example 58: N- (5-acenaphthyl) -N '-(3- (4-tert-butylben Zoyloxymethyl) phenyl) guanidine mesylate White solid; mp: 113-115 ° C; TLC (AcOEt: MeOH = 10: 1): R_f= 0.39;¹H NMR (CDCl_Three): 7. 681-7.267 (m, 11H, Ar-H), 6.904-6.875 (d, 2H, J = 8.92Hz, Ar-H), 5.067 (s, 2H, CH₂) 、 3.498-3.434 (m, 4H, CH₂CH₂) ， 2.856 (s, 3H, CH_Three), 1.278 (s, 9H, tert-butyl); HRMS: 449.2452 (C₃₀H₃₁ON_ThreeCalculated as 449.5956). Example 59: N- (5-acenaphthyl) -N '-(2- (2-indolyl) phene Nil) guanidine / HCl mp: 174-176 ℃; TLC (SiO₂, CHCl_Three: MeOH = 10: 1): R_f= 0.32;¹H NMR (CD_ThreeOD); δppm 6 .86-7.83 (m, 14H, ARH) 、 3.30-3.40 (m, 4H, CH₂); MS (E1): m / e402.2 (M⁺: C₂₇H₂N_Four); Minutes Analysis result (C₂₇H_{twenty two}N_FourHCI): Calculated: C, 70.33; H, 5.58; N, 12.16; Found: C, 70. 01; H, 5.65; N, 11.56. Example 60: N- (5-acenaphthyl) -N '-(3-bromophenyl) guani Gin / HCl mp: 204-205 ℃; TLC (SiO₂, CHCl_Three: MeOH = 10: 1): R_f= 0.20;¹H NMR (CD_ThreeOD); δppm 7. 35-7.68 (m, ArH) 、 3.4-3.5 (m, 4H, CH₂); MS (E1): m / e 365.0 (M⁺: C₁₉H₁₆N.Br); analysis Result (C₁₉H₁₆N_ThreeBr.HCl): Calculated: C, 56.67; H, 4.25; N, 10.43; Found: C, 56. 49; H, 4.43; N, 10.18. Example 61: N- (5-acenaphthyl) -N '-(2,3,4-trichlorophene Nyl) -N, N'-dimethylguanidine.HCl TLC (SO₂, CHCl_Three: MeOH = 10: 1): R_f= 0.14;¹H NMR (CD_ThreeOD); δppm 6.72-7.44 (m, 7H, A rH) ， 3.5-3.6 (s, 6H, CH_Three) 、 3.4-3.5 (m, 4H, CH₂); MS (E1): m / e 418.0 (M⁺: C_{twenty one}H₁₈N_ThreeC l_Three); Analysis result (C_{twenty one}H₁₈N_Three(As Cl.HCl): Calculated: C, 55.41; H, 4.21; N, 9.23; Found : C, 55.26; H, 4.11; N, 9.03. Example 62: N- (5-acenaphthyl) -N '-(2,3,4-trichlorophene Nyl) -N'-methylguanidine.HCl mp: 229-231 ℃; TLC (SiO₂, CHCl_Three: MeOH = 10: 1): R_f= 0.19;¹H NMR (CD_ThreeOD); δppm 7. 54-7.70 (m, 4H, Ar-H), 7.33-7.40 (m, 3H, ArH); MS (E1): m / e 403.1 (M⁺: C₂₀H₁₆N_ThreeCl) Analysis result (C₂₀H₁₆N_ThreeCl ・ HCl): Calculated: C, 54.45; H, 3.88; N, 9.52; Found: C , 54.23; H, 4.01; N, 9.36. Example 63: N- (5-acenaphthyl) -N '-(4- (2'-benzothiazo) Lu-6'-methyl) phenyl) guanidine / HCl mp: 244.5-246 ℃; TLC (SiO₂, CHCl_Three: MeOH = 10: 1): R_f= 0.23;¹H NMR (CD_ThreeOD); δppm 8.15-8.17 (m, 2H, Ar-H), 7.36-7.91 (m, 10H, ArH), 3.40-3.50 (m, 4H, CH ₂), 2.50 (s, 1H, CH _Three); MS (E1): m / e 434.1 (M⁺: C₂₇H_{twenty two}N_FourS); Analysis result (C₂₇H_{twenty two}N_Four(As S.HCl): Calculated: C, 68.85; H, 4.92; N, 11.89; Found: C, 68.66; H, 4.91; N, 11.86. Example 64: Inhibition of glutamate release   The compounds were tested for inhibition of glutamate release. Shown in the data below Thus, the compounds according to the invention are blockers of glutamate release. Professional Tocol is described in PCT / US92 / 01050, specifically in Examples 8 to 9 thereof. It is listed. In summary, test compounds were first dissolved in methanol to give 20 mM Make a raw material solution. This solution is high K⁺Dilute with buffer and base buffer and The required concentration of compound was obtained as described in I, ie 10 μM or 3 μm . All solutions, including controls, were similar in concentration to methanol. Concentrated methanol The degree never exceeded the 0.3% (v / v) buffer. Synaptosome Compounds were exposed during the wash, before superthawing and throughout the entire superthawing protocol. Synaptosomes were exposed to test organic compounds prior to glutamate release. Full time Is It was 25 seconds or less.   The relative levels of glutamate release in the presence of the identified compounds of the invention were: Shown in Table I and Table 1A below. In these tables, the compounds tested are paired In the formulas below and the corresponding formulas, the substituents R, R described in the table¹And R² Identified by. The designation "NT" in the table indicates that the compound tested for a particular assay It means that it was not done.   Many of the compounds identified in Table I and Table 1A were tested in a glutamate release assay. Tested with veratridine caused by swelling and found similar results to inhibition of glutamate release. Was perceived. The veratridine protocol that triggers the glutamate release assay is Epilepsia, 27: 490-497 (1986). Example 65: Ca flow analysis   The compound is a glutamate-releasing Ca²⁺Dependent and independent components⁴⁵Ca intake A test was conducted to find out that it was involved in blocking the harvest. Calcium intake causes ischemia It is a step in a series of consequences that occur in neuronal cell death by. See Bassaclough and Leach, Current Patents Ltd., 2-27. Ca The flow analysis protocol is as follows and the results of the assay are shown in Table II below. . Preparation of rat brain synaptosomes by Hajos, Brain Res., 93: 485 (1975). did. Synaptosomes in low potassium "LK" buffer (containing 3 mM KCl) And suspended at 2 mg / ml. Add test compound in LK to synaptosomes to Incubation was carried out at room temperature for 5 minutes at a concentration of 10 μM. Then⁴⁵Ca intake, In either LK or high potassium (150 mM KCl) with buffer, It was measured by adding an isotope. 5 seconds later,⁴⁵Quench the flow of Ca Stop with 0.9 ml of solution (LK + 10 mM EGTA). Vacuum filter the solution and filter Was washed with 15 ml of quench buffer. Control the effect of the drug, control potassium-stimulation⁴⁵C a Inhibition (or block) of influx was expressed as%. This method includes Nachsen and Blau stein, J. The method disclosed in Physiol., 361: 251-268 (1985) was applied. Inspection The results of the determination are shown in Table II below. In Table II, the test compound is the corresponding Example No. And the substituents R, R identified in the formula¹And R² Are identified in Table II. Example 66: Sodium channel block assay   The ability of the compounds of the invention to block sodium channels in mammalian cells is described below. Is illustrated by the data summarized in Table III of According to the invention It is believed that at least some compounds control glutamate release in vivo. Blocking the succitoxin binding site on the voltage-activated Na channel However, the data is proof. The assay protocol is F. Gusvosky et al., Brain Resear. ch, 518: 101-106 (1990). The following solutions were prepared: 1) Raw material solution with the following composition (expressed as g / L):                Component              amount           30 mM KCl 2.23            8 mM MgSO_Four                 0.96          250 mM Hepes Tris 59.57 (pH 7.4 with Tris base)            1M choline chloride 139.60           18mM CaCl₂                 1.99   Raw material solution, ddH₂Made in O, filtered and stored at room temperature for 4-6 weeks. Hep The es raw material was refrigerated. 2) Toxin: ddH₂1 mM tetrodotoxy dissolved in 3.1 ml O (stored at 4 ° C) 1 mg. 3) Incubation buffer having the following composition (expressing the amount of component as ml):                         Component                amount                       5.4mM KCl 9.0                       0.8 mM MgSO_Four               5.0                      50mM Hepes 10.0                     130 mM choline chloride 6.5   ddH₂0.195 ml O and the above ingredients were added to the mixture, followed by 5.5 mM glucose. 0.049 g of course was added to obtain an incubation buffer. I Incubation buffer was prepared on the day of assay. 4) Washing buffer having the following composition (expressing the amount of components as ml):                        Component                 amount                     163 mM choline chloride 163                       0.8 mM MgSO_Four               100                       1.8 mM CaCl₂               100                       5.0mM Hepes 20   ddH₂O617 ml and the above components were added to the mixture to obtain a wash buffer.Synaptosome preparation   Synaptosomes were prepared as described in Example 8 of PCT / US92 / 05050. Was prepared. Prepared synaptosomes in 1 ml aliquots (5% DMSO) Frozen at -80 ° C. Thaw the preparation immediately before the assay, dilute and filter (on the membrane) So any potential to test a relatively lipophilic compound that can be absorbed from solution 10 to 15 μg protein / filter) to avoid biological problems A total of about 1,000 cpm was obtained.Test   The specimen was prepared as the following composition and had a final volume of 200λ:   [^ThreeH] Saxitoxin 50λ: 5.9 nM (Amersham TRK.877) raw material solution ([^Three [H] saxitoxin was stored according to Amersham's recommendations) at a dilution of about 1: 300. Buddha   Test compound 20λ (ddH due to low solubility₂(Dilution of [10x] in O)   Incubation buffer 80λ   Protein 50λ: 10 to 15 μg rat synaptosome   This mixture was incubated at 37 ° C for 30 minutes and then Whatman (Wh atmann) GF / C glass fiber filter and filter with 3 ml of wash buffer Wash twice and filter punch the vial into the vial as soon as the assay is complete. did. [^ThreeH] STX is very unstable and H₂O If evaporates,^ThreeMay lose H. Scintillation liquid (CytoScint ICN # 882465) 5 ml was added and samples were counted every 5 minutes. Non-specific binding is 10 Approximately 5% of the total binding at the [protein] as determined by μM TTX.   In Table III, the test compounds are R, R of the test compounds listed in Table III.¹Oh And R²And the substituents thereof are identified in relation to the formulas set forth below. Test compound The substance is present in the form of salt as shown in the table.   The invention has been described in detail, including its preferred embodiments. However, those skilled in the art , Changes and / or improvements relating to the present invention may be made in light of the present disclosure. , Nevertheless, within the scope and spirit of the invention as defined in the following claims. You will understand that there is.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁶ Identification code Internal reference number FI A61K 31/47 AAB 9454-4C A61K 31/47 AAB C07D 209/08 9159-4C C07D 209/08 209/14 9159 -4C 209/14 215/38 7019-4C 215/38 277/64 9283-4C 277/64 307/91 7822-4C 307/91 521/00 8415-4C 521/00 // C07C 211/61 9280-4H C07C 211/61 261/04 9451-4H 261/04 (81) Designated countries EP (AT, BE, CH, DE, DK, ES, FR, GB, GR, IE, IT, LU, MC, NL, PT , SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN, ML, MR, NE, SN, TD, TG), AP (KE, MW, SD, SZ), AM, AT, AU, BB, BG, BR, BY, CA, C H, CN, CZ, DE, DK, EE, ES, FI, GB, GE, HU, JP, KE, KG, KP, KR, KZ, LK, LR, LT, LU, LV, MD, MG, MN , MW, NL, NO, NZ, PL, PT, RO, RU, SD, SE, SI, SK, TJ, TT, UA, US, UZ, VN (72) Inventor Durant, Graham J. USA Massachusetts 02050, Marshfield, Captain Luther Little Way 55 (72) Inventor Hu, Rhine-Yen, USA Massachusetts 01730, Bedford, Old Stage Coach Road Number 16 (72) Inventor Goldin, Stanley M. USA, Massachusetts 02173, Lexington, Russell Road 10 (72) Inventor Lady N. Luxmaa Rica, Massachusetts 02148, Mardan, Grover Street 24, Apartment Number 4 (72) Inventor Fisher, James Bee United States, Massachusetts 02139, Cambridge, Cambridge Street 1524 (72) Inventor Katragadda, Shubbarao United States of America, Massachusetts 02178, Belmont, Hawthorne Street 65 (72) Inventor Nap, Andrew Gunnette United States, Massachusetts 01970, Salem, Warren Street 15 (72) Inventor Margoline, Lee David United States, Massachusetts 02178, Belmont, White Street 109

Claims (1)

[Claims] 1. formula (In the formula, R and R ¹ Are each independently hydrogen, substituted or unsubstituted alkyl having 1 to about 20 carbon atoms, substituted or unsubstituted alkenyl having 2 to about 20 carbon atoms, 2 to about 20 carbons. A substituted or unsubstituted alkynyl having atoms, a substituted or unsubstituted alkoxy having 1 to about 20 carbon atoms, a substituted or unsubstituted alkylthio having 1 to about 20 carbon atoms, 1 to about 20 A substituted or unsubstituted aminoalkyl having carbon atoms, a substituted or unsubstituted alkylsulfinyl having 1 to about 20 carbon atoms, a substituted or unsubstituted alkylsulfonyl having 1 to about 20 carbon atoms, Substituted or unsubstituted carbocyclic aryl having at least about 5 ring atoms, substituted or unsubstituted having at least about 5 ring atoms Or aralkyl, or a substituted or unsubstituted heteroaromatic or heteroalicyclic having 1 to 3 rings, 3 to 8 ring members in each ring, and 1 to 3 heteroatoms. Is a formulaic group; Ar has a substituted or unsubstituted carbocyclic aryl having at least 5 carbon atoms, and 1 to 3 rings, with 3 to 8 ring members in each ring. And is selected from the group consisting of a substituted or unsubstituted heteroaromatic group having 1 to 3 heteroatoms) and a pharmaceutically acceptable salt thereof. 2. formula (In the formula, R and R ¹ Are each independently hydrogen, substituted or unsubstituted alkyl having 1 to about 20 carbon atoms, substituted or unsubstituted alkenyl having 2 to about 20 carbon atoms, 2 to about 20 carbons. A substituted or unsubstituted alkynyl having atoms, a substituted or unsubstituted alkoxy having 1 to about 20 carbon atoms, a substituted or unsubstituted alkylthio having 1 to about 20 carbon atoms, 1 to about 20 A substituted or unsubstituted aminoalkyl having carbon atoms, a substituted or unsubstituted alkylsulfinyl having 1 to about 20 carbon atoms, a substituted or unsubstituted alkylsulfonyl having 1 to about 20 carbon atoms, Substituted or unsubstituted carbocyclic aryl having at least about 5 ring atoms, substituted or unsubstituted having at least about 5 ring atoms Or aralkyl, or a substituted or unsubstituted heteroaromatic or heteroalicyclic having 1 to 3 rings, 3 to 8 ring members in each ring, and 1 to 3 heteroatoms. Is a formulaic group; Ar has a substituted or unsubstituted carbocyclic aryl having at least 5 carbon atoms, and 1 to 3 rings, with 3 to 8 ring members in each ring. And is selected from the group consisting of a substituted or unsubstituted heteroaromatic group having 1 to 3 heteroatoms) and a pharmaceutically acceptable salt thereof. 3. Ar is independently at one or more positions halo, haloalkyl, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkoxy, nitro and The compound of claim 1 or 2 which is phenyl substituted with a group selected from substituted or unsubstituted carbocyclic aryl. 4. Ar is substituted with a substituted or unsubstituted aralkyl, a substituted or unsubstituted aralkylamino, a substituted or unsubstituted aryloxy, a substituted or unsubstituted alkyleneoxyaryl, or a substituted or unsubstituted heterocyclic group. The compound of claim 1 or 2 which is phenyl. 5. Ar is a substituted or unsubstituted anthracenyl, a substituted or unsubstituted indolinyl, a substituted or unsubstituted fluorenyl, a substituted or unsubstituted biphenyl, a substituted or unsubstituted dibenzofuranyl, or a substituted or unsubstituted tetralinyl. A compound of Item 1 or 2. 6. A compound according to claim 1 or 2 selected from the following groups and pharmacologically acceptable salts of these compounds. N- (5-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) guanidine; N- (5-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N, N'-dimethylguanidine; N, N'-bis (5-acenaphthyl) -N-methylguanidine; N, N'-bis (5-acenaphthyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(1-anthracenyl) guanidine; N- (5-acenaphthyl) -N '-(1-anthracenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(1-anthracenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(1-anthracenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(4-tert-butylphenyl) guanidine; N- (5-acenaphthyl) -N '-(4-tert-butylphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(4-tert-butylphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(4-tert-butylphenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(4-cyclohexylphenyl) guanidine; N- (5-acenaphthyl) -N '-(4-cyclohexylphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(4-cyclohexylphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(4-cyclohexylphenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(4-sec-butylphenyl) guanidine; N- (5-acenaphthyl) -N '-(4-sec-butylphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(4-sec-butylphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(4-sec-butylphenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(4-methoxyphenyl) guanidine; N- (5-acenaphthyl) -N '-(4-methoxyphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(4-methoxyphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(4-methoxyphenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(2 3-dichlorophenyl) guanidine; N- (5-acenaphthyl) -N '-(2 3-dichlorophenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(2 3-dichlorophenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(2 3-dichlorophenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(4-methoxy-2-naphthyl) guanidine; N- (5-acenaphthyl) -N '-(4-methoxy-2-naphthyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(4-methoxy-2-naphthyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(4-methoxy-2-naphthyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(3 4-dichlorophenyl) guanidine; N- (5-acenaphthyl) -N '-(3 4-dichlorophenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(3 4-dichlorophenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(3 4-dichlorophenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(4-chlorophenyl) guanidine; N- (5-acenaphthyl) -N '-(4-chlorophenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(4-chlorophenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(4-chlorophenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(2-naphthyl) guanidine; N- (5-acenaphthyl) -N '-(2-naphthyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(2-naphthyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(2-naphthyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(6-quinolinyl) guanidine; N- (5-acenaphthyl) -N '-(6-quinolinyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(6-quinolinyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(6-quinolinyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(4-nitrophenyl) guanidine; N- (5-acenaphthyl) -N '-(4-nitrophenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(4-nitrophenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(4-nitrophenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(3-biphenyl) guanidine; N- (5-acenaphthyl) -N '-(3-biphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(3-biphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(3-biphenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(2 3-dimethylphenyl) guanidine; N- (5-acenaphthyl) -N '-(2 3-dimethylphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(2 3-dimethylphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(2 3-dimethylphenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(2-biphenyl) guanidine; N- (5-acenaphthyl) -N '-(2-biphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(2-biphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(2-biphenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(2 5-dibromophenyl) guanidine; N- (5-acenaphthyl) -N '-(2 5-dibromophenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(2 5-dibromophenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(2 5-dibromophenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(3 4-dimethoxyphenyl) guanidine; N- (5-acenaphthyl) -N '-(3 4-dimethoxyphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(3 4-dimethoxyphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(3 4-dimethoxyphenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(4-methoxy-1-naphthyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(4-methoxy-1-naphthyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(4-methoxy-1-naphthyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(4-chloro-1-naphthyl) guanidine; N- (5-acenaphthyl) -N '-(4-chloro-1-naphthyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(4-chloro-1-naphthyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(4-chloro-1-naphthyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) guanidine; N- (5-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(4-biphenyl) guanidine; N- (5-acenaphthyl) -N '-(4-biphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(4-biphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(4-biphenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl) guanidine; N- (5-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(3-isopropylphenyl) guanidine; N- (5-acenaphthyl) -N '-(3-isopropylphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(3-isopropylphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(3-isopropylphenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(3-tert-butylphenyl) guanidine; N- (5-acenaphthyl) -N '-(3-tert-butylphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(3-tert-butylphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(3-tert-butylphenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl) guanidine; N- (5-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(3-iodophenyl) guanidine; N- (5-acenaphthyl) -N '-(3-iodophenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(3-iodophenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(3-iodophenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(3-nitrophenyl) guanidine; N- (5-acenaphthyl) -N '-(3-nitrophenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(3-nitrophenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(3-nitrophenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(5-indolinyl) guanidine; N- (5-acenaphthyl) -N '-(5-indolinyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(5-indolinyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(5-indolinyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(3-acenaphthyl) guanidine; N- (5-acenaphthyl) -N '-(3-acenaphthyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(3-acenaphthyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(3-acenaphthyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(2-fluorenyl) guanidine; N- (5-acenaphthyl) -N '-(2-fluorenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(2-fluorenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(2-fluorenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(4-n-butoxyphenyl) guanidine; N- (5-acenaphthyl) -N '-(4-n-butoxyphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(4-n-butoxyphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(4-n-butoxyphenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl) guanidine; N- (5-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(3- (2-methoxy) -dibenzofuranyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl) guanidine; N- (5-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(4-trifluoromethylphenyl) guanidine; N- (5-acenaphthyl) -N '-(4-trifluoromethylphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(4-trifluoromethylphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(4-trifluoromethylphenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(4-methylthiophenyl) guanidine; N- (5-acenaphthyl) -N '-(4-methylthiophenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(4-methylthiophenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(4-methylthiophenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '(3-sec-butylphenyl) guanidine; N- (5-acenaphthyl) -N '-(3-sec-butylphenyl) -N-methylguanidine; N- (5-acenaphthyl) -N '-(3-sec-butylphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N '-(3-sec-butylphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) guanidine; N- (3-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(2 Three 4-trichlorophenyl) -N, N'-dimethylguanidine; N, N'-bis (3-acenaphthyl) -N-methylguanidine; N, N'-bis (3-acenaphthyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(1-anthracenyl) guanidine; N- (3-acenaphthyl) -N '-(1-anthracenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(1-anthracenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(1-anthracenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(4-tert-butylphenyl) guanidine; N- (3-acenaphthyl) -N '-(4-tert-butylphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(4-tert-butylphenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(4-tert-butylphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(4-cyclohexylphenyl) guanidine; N- (3-acenaphthyl) -N '-(4-cyclohexylphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(4-cyclohexylphenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '(4-cyclohexylphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(4-sec-butylphenyl) guanidine; N- (3-acenaphthyl) -N '-(4-sec-butylphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(4-sec-butylphenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(4-sec-butylphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(4-methoxyphenyl) guanidine; N- (3-acenaphthyl) -N '-(4-methoxyphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(4-methoxyphenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(4-methoxyphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(2 3-dichlorophenyl) guanidine; N- (3-acenaphthyl) -N '-(2 3-dichlorophenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(2 3-dichlorophenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(2 3-dichlorophenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(4-methoxy-2-naphthyl) guanidine; N- (3-acenaphthyl) -N '-(4-methoxy-2-naphthyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(4-methoxy-2-naphthyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(4-methoxy-2-naphthyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(3 4-dichlorophenyl) guanidine; N- (3-acenaphthyl) -N '-(3 4-dichlorophenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(3 4-dichlorophenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(3 4-dichlorophenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(4-chlorophenyl) guanidine; N- (3-acenaphthyl) -N '-(4-chlorophenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(4-chlorophenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(4-chlorophenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(2-naphthyl) guanidine; N- (3-acenaphthyl) -N '-(2-naphthyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(2-naphthyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(2-naphthyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(6-quinolinyl) guanidine; N- (3-acenaphthyl) -N '-(6-quinolinyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(6-quinolinyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(6-quinolinyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(4-nitrophenyl) guanidine; N- (3-acenaphthyl) -N '-(4-nitrophenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(4-nitrophenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(4-nitrophenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(3-biphenyl) guanidine; N- (3-acenaphthyl) -N '-(3-biphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(3-biphenyl) -N'methylguanidine; N- (3-acenaphthyl) -N '-(3-biphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(2 3-dimethylphenyl) guanidine; N- (3-acenaphthyl) -N '-(2 3-dimethylphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(2 3-dimethylphenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(2 3-dimethylphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(2-biphenyl) guanidine; N- (3-acenaphthyl) -N '-(2-biphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(2-biphenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(2-biphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(2 5-dibromophenyl) guanidine; N- (3-acenaphthyl) -N '-(2 5-dibromophenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(2 5-dibromophenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(2 5-dibromophenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(3 4-dimethoxyphenyl) guanidine; N- (3-acenaphthyl) -N '-(3 4-dimethoxyphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(3 4-dimethoxyphenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(3 4-dimethoxyphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(4-methoxy-1-naphthyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(4-methoxy-1-naphthyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(4-methoxy-1-naphthyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(4-chloro-1-naphthyl) guanidine; N- (3-acenaphthyl) -N '-(4-chloro-1-naphthyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(4-chloro-1-naphthyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(4-chloro-1-naphthyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) guanidine; N- (3-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(3 4, 5-trichlorophenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(4-biphenyl) guanidine; N- (3-acenaphthyl) -N '-(4-biphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(4-biphenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(4-biphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl) guanidine; N- (3-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(2 Three 4, 5-tetrachlorophenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(3-isopropylphenyl) guanidine; N- (3-acenaphthyl) -N '-(3-isopropylphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(3-isopropylphenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(3-isopropylphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(3-tert-butylphenyl) guanidine; N- (3-acenaphthyl) -N '-(3-tert-butylphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(3-tert-butylphenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(3-tert-butylphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl) guanidine; N- (3-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(2 Three 5, 6-tetrachlorophenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(3-iodophenyl) guanidine; N- (3-acenaphthyl) -N '-(3-iodophenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(3-iodophenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(3-iodophenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(3-nitrophenyl) guanidine; N- (3-acenaphthyl) -N '-(3-nitrophenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(3-nitrophenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(3-nitrophenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(5-indolinyl) guanidine; N- (3-acenaphthyl) -N '-(5-indolinyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(5-indolinyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(5-indolinyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(2-fluorenyl) guanidine; N- (3-acenaphthyl) -N '-(2-fluorenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(2-fluorenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(2-fluorenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(4-n-butoxyphenyl) guanidine; N- (3-acenaphthyl) -N '-(4-n-butoxyphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(4-n-butoxyphenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(4-n-butoxyphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl) guanidine; N- (3-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(3- (2-methoxy) dibenzofuranyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl) guanidine; N- (3-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(9-hydroxy-2-fluorenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(4-trifluoromethylphenyl) guanidine; N- (3-acenaphthyl) -N '-(4-trifluoromethylphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(4-trifluoromethylphenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(4-trifluoromethylphenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(4-methylthiophenyl) guanidine; N- (3-acenaphthyl) -N '-(4-methylthiophenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(4-methylthiophenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N '-(4-methylthiophenyl) -N, N'-dimethylguanidine; N- (3-acenaphthyl) -N '-(3-sec-butylphenyl) guanidine; N- (3-acenaphthyl) -N '-(3-sec-butylphenyl) -N-methylguanidine; N- (3-acenaphthyl) -N '-(3-sec-butylphenyl) -N'-methylguanidine; And N- (3-acenaphthyl) -N '-(3-sec-butylphenyl) -N, N'-dimethylguanidine. 7. A compound according to claim 1 or 2 selected from the following groups and pharmacologically acceptable salts of these compounds. N- (5-acenaphthyl) -N '-(4-benzyloxyphenyl) guanidine; N- (5-acenaphthyl) -N'-(3-benzyloxyphenyl) guanidine; N- (5-acenaphthyl) -N ' -(3-sec-butylphenyl) guanidine; N- (5-acenaphthyl) -N '-(2-anthracenyl) guanidine; N- (5-acenaphthyl) -N'-(3-phenethylphenyl) guanidine; N- (5-acenaphthyl) -N '-(4-adamantylphenyl) guanidine; N- (5-acenaphthyl) -N'-(3-benzyloxyphenyl) -N'-methylguanidine; N- (5-acenaphthyl)- N '-(4-benzyloxyphenyl) -N'-methylguanidine; N- (5-acenaphthyl) -N'-(3-biphenyl) -N'- Methylguanidine; N- (5-acenaphthyl) -N '-(3- (1'-methyl-2'-phenylethyl) phenyl) guanidine; N- (5-acenaphthyl) -N'-(3,4-tetra Linylphenyl) guanidine; N- (5-acenaphthyl) -N '-(7-benzyltetralinylphenyl) guanidine; N- (5-acenaphthyl) -N'-(3- (1- (4-ethoxyphenyl) ) Propyl) phenyl) guanidine; N- (5-acenaphthyl) -N '-(3- (N ", N" -dibenzylamino) phenyl) guanidine; N- (5-acenaphthyl) -N'-(3- (1'-benzylbutyl) phenyl) guanidine; N- (5-acenaphthyl) -N'-3- (4-tert-butylbenzoyloxymethyl) phenyl) guanidine; N- (5-acene Futyl) -N '-(2- (2-indolyl) phenyl) guanidine; N- (5-acenaphthyl) -N'-(3-bromophenyl) guanidine; N- (5-acenaphthyl) -N '-(2 , 3,4-Trichlorophenyl) -N, N'-dimethylguanidine; N- (5-acenaphthyl) -N '-(2,3,4-trichlorophenyl) -N'-methylguanidine; N- (5- Acenaphthyl) -N '-(3,4-dibenzyloxyphenyl) guanidine; N- (5-acenaphthyl) -N'-(4- (2'-benzothiazole-6'-methyl) phenyl) guanidine; N- (3-acenaphthyl) -N '-(4-benzoyloxyphenyl) guanidine; N- (3-acenaphthyl) -N'-(3-benzoyloxyphenyl) guanidine; N- (3 Acenaphthyl) -N '-(3-sec-butylphenyl) guanidine; N- (3-acenaphthyl) -N'-(2-anthracenyl) guanidine; N- (3-acenaphthyl) -N '-(3-phenethylphenyl ) Guanidine; N- (3-acenaphthyl) -N '-(4-adamantylphenyl) guanidine; N- (3-acenaphthyl) -N'-(3-benzyloxyphenyl) -N'-methylguanidine; N- ( 3-acenaphthyl) -N '-(4-benzyloxyphenyl) -N'-methylguanidine; N- (3-acenaphthyl) -N'-(3-biphenyl) -N'-methylguanidine; N- (3- Acenaphthyl) -N '-(3- (1'-methyl-2'-phenylethyl) phenyl) guanidine; N- (3-acenaphthyl) -N'-(3,4 Tetralinylphenyl) guanidine; N- (3-acenaphthyl) -N '-(7-benzyltetralinylphenyl) guanidine; N- (3-acenaphthyl) -N'-(3- (1- (4-ethoxy) Phenyl) propyl) phenyl) guanidine; N- (3-acenaphthyl) -N '-(3- (N ", N" -dibenzylamino) phenyl) guanidine; N- (3-acenaphthyl) -N'-(3 -(1'-benzylbutyl) phenyl) guanidine; N- (3-acenaphthyl) -N '-(3- (4-tert-butylbenzoyloxymethyl) phenyl) guanidine; N- (3-acenaphthyl) -N' -(2- (2-Indolyl) phenyl) guanidine; N- (3-acenaphthyl) -N '-(3-bromophenyl) guanidine; N- (3-acenaphthyl)- N '-(3,4-dibenzyloxyphenyl) guanidine; N- (3-acenaphthyl) -N'-(2,3,4-trichlorophenyl) -N, N'-dimethylguanidine; N- (3- Acenaphthyl) -N '-(2,3,4-trichlorophenyl) -N'-methylguanidine; and N- (3-acenaphthyl) -N'-(4- (2'-benzothiazole-6'-methyl). Phenyl) guanidine. 8. formula (In the formula, R and R ¹ Are each independently hydrogen, substituted or unsubstituted alkyl having 1 to about 20 carbon atoms, substituted or unsubstituted alkenyl having 2 to about 20 carbon atoms, 2 to about 20 carbons. A substituted or unsubstituted alkynyl having atoms, a substituted or unsubstituted alkoxy having 1 to about 20 carbon atoms, a substituted or unsubstituted alkylthio having 1 to about 20 carbon atoms, 1 to about 20 A substituted or unsubstituted aminoalkyl having carbon atoms, a substituted or unsubstituted alkylsulfinyl having 1 to about 20 carbon atoms, a substituted or unsubstituted alkylsulfonyl having 1 to about 20 carbon atoms, Substituted or unsubstituted carbocyclic aryl having at least about 5 ring atoms, substituted or unsubstituted having at least about 5 ring atoms Or aralkyl, or a substituted or unsubstituted heteroaromatic or heteroalicyclic having 1 to 3 rings, 3 to 8 ring members in each ring, and 1 to 3 heteroatoms. Is a formula group; R ² Are each independently halogen, hydroxyl, cyano, isocyanato, nitro, amino, azido, substituted or unsubstituted alkyl having 1 to about 20 carbon atoms, substituted or unsubstituted having 2 to about 20 carbon atoms, or Unsubstituted alkenyl, substituted or unsubstituted alkynyl having 2 to about 20 carbon atoms, substituted or unsubstituted alkoxy having 1 to about 20 carbon atoms, substituted having 1 to about 20 carbon atoms Or unsubstituted alkylthio, substituted or unsubstituted alkylsulfinyl having 1 to about 20 carbon atoms, substituted or unsubstituted alkylsulfonyl having 1 to about 20 carbon atoms, 1 to about 20 carbon atoms A substituted or unsubstituted aminoalkyl having, or a substituted or unsubstituted having at least about 5 ring atoms. N is 1, 2, 3, 4, 5, 6, 7, 8 or 9; Ar is a substituted or unsubstituted carbocyclic aryl having at least 5 carbon atoms, and 1 To 3 rings, having 3 to 8 ring members in each ring, and selected from the group consisting of substituted or unsubstituted heteroaromatic groups having 1 to 3 heteroatoms) Or a pharmacologically acceptable salt thereof. 9. formula (In the formula, R and R ¹ Are each independently hydrogen, substituted or unsubstituted alkyl having 1 to about 20 carbon atoms, substituted or unsubstituted alkenyl having 2 to about 20 carbon atoms, 2 to about 20 carbons. A substituted or unsubstituted alkynyl having atoms, a substituted or unsubstituted alkoxy having 1 to about 20 carbon atoms, a substituted or unsubstituted alkylthio having 1 to about 20 carbon atoms, 1 to about 20 A substituted or unsubstituted aminoalkyl having carbon atoms, a substituted or unsubstituted alkylsulfinyl having 1 to about 20 carbon atoms, a substituted or unsubstituted alkylsulfonyl having 1 to about 20 carbon atoms, at least about Substituted or unsubstituted carbocyclic aryl having 5 ring atoms, substituted or unsubstituted having at least about 5 ring atoms Aralkyl, or substituted or unsubstituted heteroaromatic or heteroalicyclic having 1 to 3 rings, having 3 to 8 ring members in each ring, and having 1 to 3 heteroatoms Is a group; R ² Are each independently halogen, hydroxyl, cyano, isocyanato, nitro, amido, azido, substituted or unsubstituted alkyl having 1 to about 20 carbon atoms, substituted or unsubstituted having 2 to about 20 carbon atoms, or Unsubstituted alkenyl, substituted or unsubstituted alkynyl having 2 to about 20 carbon atoms, substituted or unsubstituted alkoxy having 1 to about 20 carbon atoms, substituted having 1 to about 20 carbon atoms Or unsubstituted alkylthio, substituted or unsubstituted alkylsulfinyl having 1 to about 20 carbon atoms, substituted or unsubstituted alkylsulfonyl having 1 to about 20 carbon atoms, 1 to about 20 carbon atoms A substituted or unsubstituted aminoalkyl having, or a substituted or unsubstituted having at least about 5 ring atoms Aralkyl; n is 1, 2, 3, 4, 5, 6, 7, 8 or 9; Ar is a substituted or unsubstituted carbocyclic aryl having at least 5 carbon atoms; Selected from the group consisting of substituted or unsubstituted heteroaromatic groups having 3 rings, having 3 to 8 ring members in each ring, and 1 to 3 heteroatoms). The compound shown or a pharmaceutically acceptable salt thereof. 10. A method of treating or preventing a disorder of the nervous system in which the pathophysiology of the disorder involves excessive release of neurotransmitters from neuronal cells, which exhibits the symptoms of the disorder, or to mammals susceptible to the disorder, A method of administering an effective amount of a compound of claim 1, 2, 8 or 9. 11. Disorders are 1) nausea resulting from chemotherapy, 2) epilepsy, 3) convulsions, 4) carbon monoxide poisoning, 5) cyanide poisoning, 6) toxic brain damage caused by tetrodotoxin or seafood poison, 7) amnesia. , 8) Migraine or ocular onchocerciasis, or 9) Hypoxia, hypoglycemia, cerebral or spinal cord ischemia, cerebral or spinal cord injury, stroke, heart attack, or nerve cell death resulting from drowning. Item 10. The method according to Item 10. 12. A method of treating or preventing nerve cell death, which comprises administering an effective amount of the compound of claim 1, 2, 8 or 9 to a subject who exhibits symptoms of nerve cell death or is susceptible to nerve cell death. . 13. A method of modulating the release of excess endogenous neurotransmitter from a subject, the method comprising administering to the subject an effective amount of a compound of claim 1, 2, 8 or 9. 14． A method of blocking voltage-sensitive calcium channels in mammalian neuronal cells, the method comprising administering to the cells an effective amount of a compound of claim 1, 2, 8 or 9. 15. A method of blocking voltage-sensitive sodium channels in mammalian neuronal cells, the method comprising administering to the cells an effective amount of a compound of claim 1, 2, 8 or 9. 16. A pharmaceutical composition comprising a therapeutically effective amount of one or more compounds of claims 1, 2, 8 or 9 and a pharmaceutically acceptable carrier.