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Nitrogen-containing cyclic compound and pharmaceutical composition containing the compoundRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai, Hetero Ring Is Six-membered Consisting Of Two Nitrogens And Four Carbon Atoms (e.g., Pyridazines, Etc.), 1,4-diazine As One Of The Cyclos, Piperazines (i.e., Fully Hydrogenated 1,4-diazines), Additional Hetero Ring Attached Directly Or Indirectly To The Piperazine Ring By Nonionic BondingNitrogen-containing cyclic compound and pharmaceutical composition containing the compound description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060084658, Nitrogen-containing cyclic compound and pharmaceutical composition containing the compound. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a Divisional of co-pending U.S. application Ser. No. 10/855,357 filed on May 28, 2004, which is a Divisional of U.S. application Ser. No. 10/169,837 filed Jul. 10, 2002, and for which priority is claimed under 35 U.S.C. .sctn. 120; U.S. application Ser. No. 10/169,837 is the National Phase of International Application No. PCT/JP01/00288 having an international filing date of Jan. 18, 2001, which claims priority of Application No. 2000-12176 filed in Japan on Jan. 20, 2000 under 35 U.S.C. .sctn. 119; the entire contents of all above are hereby incorporated by reference. TECHNICAL FIELD [0002] The present invention relates to a novel compound useful as a calcium antagonist, a salt thereof, a hydrate of them, a production process thereof, and a pharmaceutical composition thereof; and specifically relates to a neuron-selective calcium antagonist, in particular a novel compound having a P/Q-type calcium channel and/or an N-type calcium channel inhibiting activity, etc. PRIOR ART [0003] In Japan, the number of patients with cerebral apoplexy is about 1.4 million or more per year, and the medical expenses therefor are estimated to be about two billion yen. Cerebral apoplexy is the second cause of death next to malignant tumor and is the biggest cause for bedridden man often suffering from severe secondary diseases. A key to the treatment of cerebral apoplexy is to deal with the acute stage, and the treatment at the acute stage influences the life and function prognosis of the patient and significantly influences secondary diseases. [0004] For the purpose of improving blood stream, several drugs such as ozagrel sodium (thromboxane synthase inhibitor), argatroban (anti-thrombin agent) as an agent for treatment of chronic arterial occlusion, t-PA (alteplase: tissue plasminogen activator which should be used within 3 hours after the onset) as thrombolytic agent etc. are now approved of, or in off lavel use. However, the therapy according to a conventional medicine is the complicate procedures as described in (1) to (6), and cautious judgment by a specialist on the basis of enough knowledge and experience has been required. Namely, (1) in the case of thrombus-type cerebral infarction, respiratory control, blood pressure control and blood transfusion control are first conducted. (2) Blood gas and blood pressure are periodically measured. (3) At the acute stage, reactive high blood pressure is observed, but if complications in the heart and kidney are not observed, treatment for decreasing blood pressure is not conducted. (4) Then, in the early-acute stage case with no low absorption range observed in CT, the thrombus-lytic agent "urokinase" is used. (5) In the case where these agents are not applicable or in the case where 24 hours or more has elapsed after the onset, "ozagrel sodium" is administered. Or "argatroban" is administered. However, argatroban is not applicable to lacuna infarction. (6) To prevent the development of cerebral edema, "glycerin" or "mannitol" is administered at a suitable dosage. [0005] Further, the therapeutic effects of the drugs used heretofore are not satisfactory and further there is the danger that bleeding is often accompanied by their pharmacological effect. Accordingly, there is the problem that it is difficult for those except of skilled medical specialists to use these drugs. [0006] On the other hand, the following literatures describe that compounds having an inhibitory action on N type or P/Q type calcium channels can serve as an agent for inhibiting the death of neural cells or for protecting cerebral neural cells, an agent for treating or improving nervous diseases, an agent for treating or improving acute ischemic stroke, head trauma, death of neural cells, Alzheimer disease, cerebral circulatory metabolism disturbance, cerebral function disturbance or pain, an anti-spasm agent, an agent for treating or improving schizophrenia and an agent for preventing, treating or improving migraine, epilepsy, maniac-depressive psychosis, neural degenerative diseases (Parkinson disease, Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease), cerebral ischemia, epilepsy, head trauma, AIDS dementia complications, edema, anxiety disorder (generalized anxiety disorder) and diabetic neuropathy, and as an agent for preventing, treating or improving edema, anxiety disorder, schizophrenia, diabetic neuropathy and migraine. [0007] (1) Acute ischemia stroke: Annj. Rev. Physiol., 52 543-559, 1990. [0008] (2) Head trauma: SCRIP, No. 2203, 24, 1997. [0009] (3) Ischemia--death of cerebral neural cells: Advances in Pharmacology, 22, 271-297, 1991. [0010] (4) Alzheimer disease: Trends in Neuroscience, 16, 409, 1993. [0011] (5) Cerebral circulatory metabolism disturbance: Nichiyakurishi, 85, 323-328, 1985. [0012] (6) Cerebral function disturbance: Acta Neurol. Scand., 78:2, 14-200, 1998. [0013] (7) Analgesic: Drug of the Future, 23(2), 152-160, 1998. [0014] (8) Cerebral ischemia, migraine, epilepsy, maniac-depressive psychosis: Casopis Lekau Ceskych., 130(22-23), 625-630, 1991. [0015] (9) Neural degenerative diseases (Parkinson disease, Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease), cerebral ischemia, epilepsy, head trauma, and AIDS dementia complications: Revista de Neurologia., 24(134), 1199-1209, 1996. [0016] (10) Edema: Brain Research, 776, 140-145, 1997. [0017] (11) Anxiety disorder (generalized anxiety disorder), schizophrenia: Jyunkanseigyo (Circulation Control), 14 (2), 139-145, 1993. [0018] (12) Diabetic neuropathy: Shinkeinaika (Neurological Medicine), 50, 423-428, 1999. [0019] (13) Migraine: Neurology, 50(4), 1105-1110, 1998. DISCLOSURE OF THE INVENTION [0020] In light of this, the present inventors have intensively studied for investigating a preparation which has a superior effect of treatment and amelioration for cerebral acute ischemic stroke for which no useful preparation is not found and has high safety which does not cause bloodshed tendency, focusing on a neuron-selective, potential-dependent calcium channel antagonist which directly effects on neural cell and inhibits the progression of infarction nidus. As a result, the present inventors have succeeded in synthesizing a novel nitrogen-containing compound which is represented by the formula (I), a salt thereof and a hydrate thereof, and further surprisingly have found that these compounds, a salt thereof or a hydrate thereof have the superior suppression action of neural cell death and protective action of cerebral neuron based on the P/Q type or N-type calcium channel antagonism, that cell infarction property and toxicity are remarkably reduced in comparison with a conventional calcium antagonist and that the compound and the like are superior in safety, and have completed the present invention. [0021] In the formula, Ar is (1) a C.sub.6-14 aromatic hydrocarbon cyclic group which may be substituted, (2) a 5- to 14-membered aromatic heterocyclic group which may be substituted, (3) a C.sub.1-6 alkyl group substituted with a C.sub.6-14 aromatic hydrocarbon cyclic group which may be substituted or (4) a C.sub.1-6 alkyl group substituted with a 5- to 14-membered aromatic heterocyclic group which may be substituted; the ring A indicates a piperazine ring, homopiperazine ring, piperidine ring, homopiperidine ring, pyrrolidine ring or diazabicyclo[2,2,1]heptane ring which may be substituted, respectively; the ring B indicates (1) a C.sub.3-14 hydrocarbon ring which may be substituted or (2) a 5- to 14-membered heterocyclic ring which may be substituted; E indicates (1) a single bond, a group represented by the formula (2) --CO-- or (3) --CH(OH)--; X indicates (1) a single bond, (2) an oxygen atom, (3) a sulfur atom, (4) a C.sub.1-6 alkylene chain which may be substituted, a group represented by (5) the formula --NR.sup.2-- (wherein R.sup.2 indicates a hydrogen atom, or a C.sub.1-6 alkyl group, a C.sub.3-8 cycloalkyl group, a lower acyl group or a C.sub.1-6 alkylsulfonyl group which may be substituted), (6) --CO--, (7) --COO--, (8) --OOC--, (9) --CONR.sup.3-- (wherein R.sup.3indicates a hydrogen atom or a C.sub.1-6 alkyl group which may be substituted), (10) --NR.sup.4CO-- (wherein R.sup.4 indicates a hydrogen atom or a C.sub.1-6 alkyl group which may be substituted), (11) --SO--, (12) --SO.sub.2--, (13) --SONR.sup.5-- (wherein R.sup.5 indicates a hydrogen atom or a C.sub.1-6 alkyl group which may be substituted), (14) --NR.sup.6SO-- (wherein R.sup.6 indicates a hydrogen atom or a C.sub.1-6 alkyl group which may be substituted), (15) --SO.sub.2NR.sup.7-- (wherein R.sup.7 indicates a hydrogen atom or a C.sub.1-6 alkyl group which may be substituted), (16) --NR.sup.8SO.sub.2-- (wherein R.sup.8 indicates a hydrogen atom or a C.sub.1-6 alkyl group which may be substituted), (17) >C.dbd.N--OR.sup.9 (wherein R.sup.9 indicates a hydrogen atom or a C.sub.1-6 alkyl group which may be substituted), (18) --NR.sup.10--W.sup.3--O-- (wherein R.sup.10 indicates a hydrogen atom or a C.sub.1-6 alkyl group, a C.sub.3-8cycloalkyl group, a lower acyl group or a C.sub.1-6 alkylsulfonyl group which may be substituted; and W.sup.3 indicates a C.sub.1-6 alkylene group which may be substituted), (19) --NH--CO--NH--, (20) --NH--CS--NH--, (21) --C(.dbd.NR.sup.15)NR.sup.16-- (wherein R.sup.15 and R.sup.16 are the same as or different from each other and each indicates a hydrogen atom, nitrile group, a C.sub.1-6 alkyl group, a C.sub.2-6 alkenyl group, a C.sub.3-8 cycloalkyl group or a C.sub.3-8 cycloalkenyl group), (22) --NHC(.dbd.NH) --, (23) --O--CO--S--, (24) --S--CO--O--, (25) --OCOO--, (26) --NHCOO--, (27) --OCONH--, (28) --CO(CH.sub.2).sub.mO-- (wherein m indicates 0 or an integer of 1 to 6), (29) --CHOH-- or (30) --CHOH(CH.sub.2).sub.nO-- (wherein n indicates 0 or an integer of 1 to 6); R.sup.1 indicates (1) a hydrogen atom, (2) a halogen atom, (3) hydroxyl group, (4) a C.sub.1-6 alkyl group which may be substituted with one or more groups selected from hydroxyl group, a halogen atom and nitrile group, (5) a C.sub.2-6 alkenyl group which may be substituted with one or more groups selected from hydroxyl group, a halogen atom and nitrile group, (6) a C.sub.2-6 alkynyl group which may be substituted with one or more groups selected from hydroxyl group, a halogen atom and nitrile group, (7) a C.sub.3-8 cycloalkyl group which may be substituted with one or more groups selected from hydroxyl group, a halogen atom and nitrile group, (9) a C.sub.1-6 alkoxy-C.sub.1-6 alkyl group, (10) an amino-C.sub.1-6 alkyl group in which the nitrogen may be substituted, (11) a group represented by the formula --N(R.sup.11)R.sup.12-- (wherein R.sup.1 and R.sup.12 are the same as or different from each other and each indicates a hydrogen atom or a C.sub.1-6 alkyl group), (12) an aralkyl group, (13) morpholinyl group, (14) thiomorpholinyl group, (15) piperidyl group, (16) a pyrrolidinyl group or (17) a piperazinyl group; and D.sup.1, D.sup.2, W.sup.1 and W.sup.2 are the same as or different from each other and each indicates (1) a single bond or (2) a C.sub.1-6 alkylene chain which may be substituted, [0022] provided that, in the above definition, 1-[4-cyano-5-methyl-4-(2-cyano-5-thienyl)hexyl]-4-[2-(4-fluorophenoxy)eth- yl]piperazine; 1-[4-cyano-5-methyl-4-(2-cyano-5-thienyl)hexyl]-4-[2-(3-fluorophenoxy)eth- yl]piperazine; and 1-[4-cyano-5-methyl-4-(2-thienyl)hexyl]-4-[2-(3-fluorophenoxy)ethyl]piper- azine are excluded. [0023] Namely, the first aspect of the present invention is 1) a compound represented by the above formula (I), a salt thereof or a hydrate of them, and further, 2) in the above-mentioned 1), Ar may be a C.sub.6-14 aromatic hydrocarbon ring or 5- to 14-membered aromatic heterocyclic ring, which may be substituted, 3) in the above-mentioned 1), Ar may be a thiophene ring or benzene ring, which may be substituted, 4) in the above 1), Ar may be a C.sub.6-14 aromatic hydrocarbon ring or 5- to 14-membered aromatic heterocyclic ring, which may be substituted with any one or more groups selected from nitrile group and a halogen atom, 5) in the above-mentioned 1), Ar may be a thiophene ring or a benzene ring which may be substituted with any one or more groups selected from nitrile group and a halogen atom, respectively, 6) in the above-mentioned 1), the ring A may be piperazine ring, homopiperazine ring or piperidine ring, 7) in the above-mentioned 1), the ring A may be a piperazine ring, 8) in the above-mentioned 1), the ring A may be a piperazine ring, a homopiperazine ring or a piperidine ring which may be substituted with any one or more groups selected from hydroxyl group, a halogen atom, cyano group, a C.sub.1-6 alkyl group which may be substituted, a C.sub.2-6 alkenyl group which may be substituted, a C.sub.2-6 alkynyl group which may be substituted, a C.sub.1-6 alkoxy group which may be substituted, a C.sub.2-6 alkenyloxy group which may be substituted, a C.sub.1-6 alkylcarbonyl group which may be substituted, a C.sub.2-6 alkenylcarbonyl group which may be substituted, a C.sub.1-6 alkoxycarbonyl group which may be substituted and a C.sub.2-6 alkenyloxycarbonyl group which may be substituted, 9) in the above-mentioned 1), the ring B may be a C.sub.6-14 aromatic hydrocarbon ring or a 5- to 14-membered aromatic heterocyclic ring which may be substituted, respectively, 10) in the above-mentioned 1), the ring B may be a benzene, a thiophene, a pyridine, a 1,4-benzodioxane, an indole, a benzothiazole, a benzoxazole, a benzimidazole, a 2-keto-1-benzimidazole, a thiazole, an oxazole, an isoxazole, a 1,2,4-oxadiazole, an indanone, a benzofuran, a quinoline, a 1,2,3,4-tetrahydroquinoline, a naphthalene or a 1,2,3,4-tetrahydronaphthalene which may be substituted, respectively, 11) in the above-mentioned 1), the ring B may be a C.sub.6-14aromatic hydrocarbon ring or a 5- to 14-membered aromatic heterocyclic ring which may be substituted with any one or more groups selected from a halogen atom, nitrile group, a C.sub.1-6 alkyl group, a lower acyl group, a C.sub.1-6 alkylsulfonyl group and an aralkyl group, respectively, 12) in the above-mentioned 1), D.sup.1 and D.sup.2 may be the same as or different from each other and each may be (1) a single bond or (2) a C.sub.1-6 alkylene chain which may be substituted with any one or more groups selected from hydroxyl group, a halogen atom, nitrile group, a C.sub.1-6 alkyl group, a C.sub.2-6 alkenyl group and a C.sub.1-6 alkoxy group, 13) in the above-mentioned 1), E may be a single bond, 14) in the above-mentioned D.sup.1 and D.sup.2 may be a C.sub.1-6 alkylene chain; and E may be a single bond, 15) in the above-mentioned 1), the partial structure -D.sup.1-E-D - may be a C.sub.1-4 alkylene group, 16) in the above-mentioned 1), W.sup.1 and W.sup.2 may be the same as or different from each other and each may be (1) a single bond or (2) a C.sub.1-6 alkylene chain which may be substituted with any one or more groups selected from hydroxyl group, a halogen atom, nitrile group, a C.sub.1-6 alkyoxy group and a C.sub.2-6 alkenyloxy group, 17) in the above-mentioned 1), W.sup.1 may be (1) a single bond or (2) a C.sub.1-6 alkylene chain which may be substituted with any one or more groups selected from (i) nitrile group, (ii) a C.sub.1-6 alkyl group which may be substituted with any one or more groups selected from a C.sub.1-6 alkoxy group and a C.sub.2-6 alkenyloxy group and (iii) a C.sub.2-6 alkenyl group; and W.sup.2 may be a single bond, 18) in the above-mentioned 1), W.sup.1 and W.sup.2 may be the same as or different from each other and each may be a C.sub.1-6 alkylene chain substituted with any one or more groups selected from a C.sub.1-6 alkyl group and a C.sub.2-6 alkenyl group, and further the above-mentioned C.sub.1-6 alkyl group and/or C.sub.2-6 alkenyl group may be bound together to form a ring or the above-mentioned C.sub.1-6 alkyl group or C.sub.2-6 alkenyl group is bound to the ring B or X to form a ring, 19) in the above-mentioned 1), X may be (1) a single bond, (2) oxygen atom, a group represented by (3) the formula --NR.sup.2-- (wherein R.sup.2 indicates a hydrogen atom, or a C.sub.1-6 alkyl group, a C.sub.3-8 cycloalkyl group, a lower acyl group or a C.sub.1-6 alkylsulfonyl group which may be substituted), (4) --NR.sup.10--W.sup.3--O-- (wherein R.sup.10 indicates a hydrogen atom, or a C.sub.1-6 alkyl group, a C.sub.3-8 cycloalkyl group, a lower acyl group or a C.sub.1-6 alkylsulfonyl group which may be substituted; and W.sup.3 is a C.sub.1-6 alkylene group which may be substituted) or (5) --NH--SO.sub.2--, 20) in the above-mentioned 1), X may be (1) oxygen atom, a group represented by (2) the formula --NR.sup.2-- (wherein R.sup.2 indicates a hydrogen atom, or a C.sub.1-6 alkyl group, a C.sub.3-8 cycloalkyl group, a lower acyl group or a C.sub.1-6 alkylsulfonyl group which may be substituted) or (3) --NH--SO.sub.2--, 21) in the above-mentioned 1), the partial structure --W.sup.1--X--W.sup.2-- may be a C.sub.1-6 alkylene group which may be substituted, 22) in the above-mentioned 1), W.sup.1 may be a C.sub.1-6 alkylene chain which may be substituted; W.sup.2is a single bond; and X may be oxygen or a group represented by the formula --NR.sup.2-- (wherein R.sup.2 has the same meaning as the above-mentioned definition), 23) in the above-mentioned 22), the substituent of W.sup.1 may be any one or more groups selected from (1) nitrile group, (2) a C.sub.1-6 alkyl group which may be substituted with a C.sub.1-6 alkyoxy group or a C.sub.2-6 alkenyloxy group and (3) a C.sub.2-6 alkenyl group; and R.sup.2 may be a C.sub.1-6 alkyl group which may be substituted, 24) in the above-mentioned 1), R.sup.1 may be a C.sub.1-6 alkyl group, 25) in the above-mentioned 1), R.sup.1 may be methyl group, ethyl group, n-propyl group or isopropyl group, 26) the compound in the above-mentioned 1) may be a compound represented by the formula: in the formula, R.sup.1 has the same meaning as in the above definition; R.sup.13 and R.sup.14 are the same as or different from each other and each indicates (1) a hydrogen atom, (2) a halogen atom, (3) hydroxyl group, (4) mercapto group, (5) a C.sub.1-6 alkyl group which may be substituted with any one or more groups selected from hydroxyl group and a halogen atom, (6) a C.sub.1-6 alkoxy group which may be substituted with any one or more groups selected from hydroxyl group, a halogen atom and a C.sub.1-6 alkoxycarbonyl group, (7) a nitro group, (8) an amino group which may be substituted, (9) cyano group, (10) carboxyl group, (11) a C.sub.1-6 alkoxycarbonyl group, (12) a C.sub.1-6 thioalkoxy group, (13) a C.sub.1-6 alkylsulfonyl group, (14) a lower acyl group, (15) a C.sub.6-14 aromatic hydrocarbon cyclic group which may be substituted, (16) a 5- to 14-membered aromatic heterocyclic group which may be optionally substituted, (17) an aryloxy group or (18) an aralkyloxy group, or (19) R.sup.13s themselves or R.sup.14s themselves may be bound together to form (i) an aliphatic ring which may be substituted, (ii) a heterocyclic ring which may be substituted or (iii) an alkylenedioxy group; n indicates 0 or an integer of 1 to 3; p indicates an integer of 1 to 6; q indicates an integer of 1 to 6; and r indicates o or an integer of 1 to 5, [0024] provided that, in the above definition, 1-[4-cyano-5-methyl-4-(2-cyano-5-thienyl)hexyl]-4-[2-(4-fluorophenoxy)eth- yl]piperazine; 1-[4-cyano-5-methyl-4-(2-cyano-5-thienyl)hexyl]-4-[2-(3-fluorophenoxy)eth- yl]piperazine; and 1-[4-cyano-5-methyl-4-(2-thienyl)hexyl]-4-[2-(3-fluorophenoxy)ethyl]piper- azine are excluded and 27) the compound in the above-mentioned 1) may be a compound represented by the formula: in the formula, R.sup.1 and R.sup.2 have the same meanings as defined above; R.sup.13 and R.sup.14 are the same as or different from each other and each indicates (1) a hydrogen atom, (2) a halogen atom, (3) hydroxyl group, (4) mercapto group, (5) a C.sub.1-6 alkyl group which may be substituted with any one or more groups selected from hydroxyl group and a halogen atom, (6) a C.sub.1-6 alkoxy group which may be substituted with any one or more groups selected from hydroxyl group, a halogen atom and a C.sub.1-6 alkoxycarbonyl group, (7) nitro group, (8) an amino group which may be substituted, (9) cyano group, (10) carboxyl group, (11) a C.sub.1-6 alkoxycarbonyl group, (12) a C.sub.1-6 thioalkoxy group, (13) a C.sub.1-6 alkylsulfonyl group, (14) a lower acyl group, (15) a C.sub.6-14 aromatic hydrocarbon cyclic group which may be substituted, (16) a 5-to 14-membered aromatic heterocyclic group which may be substituted, (17) an aryloxy group or (18) an aralkyloxy group, or (19) R.sup.13s themselves or R.sup.14s themselves may be bound together to form (i) an aliphatic ring which may be substituted, (ii) a heterocyclic ring which may be substituted or (iii) an alkylenedioxy group; n indicates 0 or an integer of 1 to 3; p indicates an integer of 1 to 6; q indicates an integer of 1 to 6; r indicates 0 or an integer of 1 to 5, and 28) in the above-mentioned 1), the compound may be any one selected from [0025] 4-[(4-cyano-5-methyl-4-phenyl)hexyl]-N-(4-fluorophenyl)-N'-(2-methylpropy- l)-1(2H)-pyrazinecarboxyimidamide; [0026] 1-isopropyl-4-[4-(1-isobutyl-1H-benzo[d]imidazol-2-yl)piperazino]-1-pheny- lbutyl cyanide; [0027] 1-[4-cyano-5-methyl-4-(5-cyano-2-thienyl)hexyl]-4-[2-(3-cyanophenoxy)ethy- l]piperazine; [0028] 1-[4-cyano-5-methyl-4-(2-thienyl)hexyl]-4-[2-(3-cyanophenoxy)ethyl]pipera- zine; [0029] 1-[4-cyano-5-methyl-4-(5-cyano-2-thienyl)hexyl]-4-[3-(5-cyano-2-thienyl)p- ropyl]piperazine; [0030] 1-[4-cyano-5-methyl-4-(3-thienyl)hexyl]-4-[2-(3-cyanophenoxy)ethyl]pipera- zine; 1-{4-cyano-5-methyl-4-[4-(2-cyano)-thienyl]hexyl}-4-[2-(3-cyanopheno- xy)ethyl]piperazine; [0031] 1-[(4-cyano-5-methyl-4-phenyl)hexyl]-4-[(2-benzoxazolyl)amino]piperidine; [0032] 1-[4-cyano-4-(5-cyano-2-thienyl)-5-methylhexyl]-(3S)-3-[N-(2-cyan- oethyl)-N-benzylamino]pyrrolidine; [0033] 1-[4-cyano-4-(5-cyano-2-thienyl)-5-methylhexyl]-(3R)-3-[N-(2-cyanoethyl)-- N-benzylamino]pyrrolidine; [0034] 1-[(4-cyano-5-methyl-4-phenyl)hexyl]-4-(benzothiazolyl]piperazine; [0035] 1-[(4-cyano-5-methyl-4-phenyl)hexyl]-4-[2-(6-methoxy)benzothiazoly- l]piperazine; [0036] 1-[(4-cyano-5-methyl-4-phenyl)hexyl]-4-(2-benzoxazolyl]piperazine; [0037] 1-[(4-cyano-5-methyl-4-phenyl)hexyl]-4-(2-quinolinyl]piperazine; [0038] 4-[4-(1-methyl-1H-benzo[d]imidazol-2-yl)-1,4-diazepan-1-yl]-1-isop- ropyl-1-phenylbutyl cyanide; [0039] 4-[4-(1-ethyl-1H-benzo[d]imidazol-2-yl)-1,4-diazepan-1-yl]-1-isopropyl-1-- phenylbutyl cyanide; ethyl [0040] 4-(4-cyano-5-methyl-4-phenylhexyl)-1-[2-(4-fluorophenoxy)ethyl]-2-piperaz- inecarboxylate; [0041] 1-[(2-oxo-1,2-dihydro-3-quinolyl)methyl]-4-[(4-cyano-5-methyl-4-phenyl)he- xyl]piperidine; [0042] 4-[(4-cyano-5-methyl-4-phenyl)hexyl]-1-{[2-(methanesulfonylamino)phenyl]m- ethyl}piperazine; [0043] 4-[(4-cyano-5-methyl-4-phenyl)hexyl]-1-{[2-(methanesulfonylamino)phenyl]m- ethyl}piperidine; [0044] (S)-3-phenyl-2-amino-propanoic acid [0045] {1-[4-cyano-5-methyl-5-(2-thionyl)hexyl]piperazinyl}amide; [0046] 4-[4-(4-phenylpiperidinyl)piperidinyl]-1-isopropyl-1-phenylbutyl cyanide; [0047] 4-[4-(4-cyano-4-phenylpiperidinyl)piperidinyl]-1-isopropyl-1-phen- ylbutyl cyanide; and [0048] 4-[4-(4-benzylpiperidinyl)piperidinyl]-1-isopropyl-1-phenylbutyl cyanide. [0049] Further, the second characteristic of the present invention is 29) a pharmaceutical composition containing the compound represented by the formula: (in the formula, Ar is (1) a C.sub.6-14 aromatic hydrocarbon cyclic group which may be substituted, (2) a 5- to 14-membered aromatic heterocyclic group which may be substituted, (3) a C.sub.1-6 alkyl group substituted with a C.sub.6-14 aromatic hydrocarbon cyclic group which may be substituted or (4) a C.sub.1-6 alkyl group substituted with a 5- to 14-membered aromatic heterocyclic group which may be substituted; the ring A indicates a piperazine ring, a homopiperazine ring, a piperidine ring, a homopiperidine ring, a pyrrolidine ring, a diazabicyclo[2,2,1]heptane ring which may be substituted, respectively; the ring B indicates (1) a C.sub.3-14 hydrocarbon ring which may be substituted or (2) a 5- to 14-membered heterocyclic ring which may be substituted; E indicates (1) a single bond, a group represented by (2) the formula --CO-- or (3) --CH(OH)--; X indicates (1) a single bond, (2) oxygen atom, (3) sulfur atom, (4) a C.sub.1-6 alkylene chain which may be substituted, a group represented by (5) the formula --NR.sup.2-- (wherein R.sup.2 indicates a hydrogen atom, or a C.sub.1-6 alkyl group, a C.sub.3-8 cycloalkyl group, a lower acyl group or a C.sub.1-6 alkylsulfonyl group which may be substituted.), (6) --CO--, (7) --COO--, (8) --OOC--, (9) --CONR.sup.3-- (wherein R.sup.3 indicates a hydrogen atom or a C.sub.1-6 alkyl group which maybe substituted), (10) --NR.sup.4CO-- (wherein R.sup.4 indicates a hydrogen atom or a C.sub.1-6 alkyl group which may be substituted), (11) --SO--, (12) --SO.sub.2--, (13) --SONR.sup.5-- (wherein R.sup.5 indicates a hydrogen atom or a C.sub.1-6 alkyl group which may be substituted), (14) --NR.sup.6SO-- (wherein R.sup.6 indicates a hydrogen atom or a C.sub.1-6 alkyl group which may be substituted), (15) --SO.sub.2NR.sup.7-- (wherein R.sup.7 indicates a hydrogen atom or a C.sub.1-6 alkyl group which may be substituted), (16) --NR.sup.8SO.sub.2-- (wherein R.sup.8 indicates a hydrogen atom or a C.sub.1-6 alkyl group which may be substituted), (17) >C.dbd.N--OR.sup.9 (wherein R.sup.9 indicates a hydrogen atom or a C.sub.1-6 alkyl group which may be substituted), (18) --NR.sup.10--W.sup.3--O-- (wherein R.sup.10 indicates a hydrogen atom, or a C.sub.1-6 alkyl group, a C.sub.3-8 cycloalkyl group, a lower acyl group or a C.sub.1-6 alkylsulfonyl group which may be substituted; and W.sup.3 indicates a C.sub.1-6 alkylene group which may be substituted), (19) --NH--CO--NH--, (20) --NH--CS--NH--, (21) --C(.dbd.NR.sup.15)NR.sup.16-- (wherein R.sup.15 and R.sup.16 are the same as or different from each other and each indicates a hydrogen atom, nitrile group, a C.sub.1-6 alkyl group, a C.sub.2-6 alkenyl group, a C.sub.3-8 cycloalkyl group or a C.sub.3-8 cycloalkenyl group), (22) --NHC(.dbd.NH)--, (23) --O--CO--S--, (24) --S--CO--O--, (25) --OCOO--, (26) --NHCOO--, (27) --OCONH--, (28) --CO(CH.sub.2).sub.mO-- (wherein m indicates 0 or an integer of 1 to 6), (29) --CHOH-- or (30) --CHOH(CH.sub.2).sub.nO-- (wherein n indicates 0 or an integer of 1 to 6.); R.sup.1indicates (1) a hydrogen atom, (2) a halogen atom, (3) hydroxyl group, (4) a C.sub.1-6 alkyl group which may be substituted with one or more groups selected from hydroxyl group, a halogen atom and nitrile group, (5) a C.sub.2-6 alkenyl group which may be substituted with one or more groups selected from hydroxyl group, a halogen atom and nitrile group, (6) a C.sub.2-6 alkynyl group which may be substituted with one or more groups selected from hydroxyl group, a halogen atom and nitrile group, (7) a C.sub.3-8 cycloalkyl group which may be substituted with one or more groups selected from hydroxyl group, a halogen atom and nitrile group, (9) a C.sub.1-6 alkoxy-C.sub.1 6 alkyl group, (10) an amino-C.sub.1-6 alkyl group in which the nitrogen atom may be substituted, (11) a group represented by the formula --N(R.sup.11)R.sup.12-- (wherein R.sup.11 and R.sup.12 are the same as or different from each other and each indicates a hydrogen atom or a C.sub.1-6 alkyl group), (12) an aralkyl group, (13) morpholinyl group, (14) thiomorpholinyl group, (15) piperidyl group, (16) pyrrolidinyl group or (17) piperazinyl group; and D.sup.1, D.sup.2, W.sup.1 and W.sup.2are the same as or different from each other and each indicates (1) a single bond or (2) a C.sub.1-6 alkylene chain which may be substituted, [0050] provided that, in the above definition, 1-[4-cyano-5-methyl-4-(2-cyano-5-thienyl)hexyl]-4-[2-(4-fluorophenoxy)eth- yl]piperazine; 1-[4-cyano-5-methyl-4-(2-cyano-5-thienyl)hexyl]-4-[2-(3-fluorophenoxy)eth- yl]piperazine; and 1-[4-cyano-5-methyl-4-(2-thienyl)hexyl]-4-[2-(3-fluorophenoxy)ethyl]piper- azine are excluded), a salt thereof or a hydrate of them, and further, 30) the composition in the above-mentioned 29) may be a calcium antagonist, 31) the composition in the above-mentioned 29) may be a neuron-selective calcium antagonist, 32) the composition in the above-mentioned 29) may be a P/Q-type calcium channel and/or an N-type calcium channel inhibitor, 33) the composition in the above-mentioned 29) may be an agent for treating, preventing or improving a disease against which the inhibitory action of at least one of P/Q-type calcium channel and N-type calcium channel is efficacious, 34) the composition in the above-mentioned 29) may be an agent for inhibiting the death of neural cell or for protecting cerebral neural cells, 35) the composition in the above-mentioned 29) may be an agent for treating, preventing or improving neural disease, 36) the neural disease in the above-mentioned 35) may be acute ischemic stroke, cerebral apoplexy, cerebral infarction, head trauma, cerebral neural cell death, Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, Huntington disease, cerebral circulatory metabolism disturbance, cerebral function disturbance, pain, spasm, schizophrenia, migraine, epilepsy, manic-depression, neural degenerative diseases, cerebral ischemia, AIDS dementia complications, edema, anxiety disorder, diabetic neuropathy, cerebral vascular dementia and multiple sclerosis and 37) the composition in the above-mentioned 29) may be an analgesic. [0051] The present invention provides a method for preventing, treating or improving a disease against which a calcium antagonism is effective, a disease against which a neuron-selective calcium antagonism is effective or a disease against which a P/Q-type calcium channel inhibitory action and/or an N-type calcium channel inhibitory action is effective, by administering a pharmacologically effective amount of the compound represetend by the above formula (I), a salt thereof or a hydrate of them to a patient. [0052] The present invention provides a method for preventing, treating or improving neural disease or pain. [0053] Further, the present invention provides use of the compound represented by the above formula (I), a salt thereof or a hydrate of them for producing a calcium antagonist, a neuron-selective calcium antagonist, a P/Q-type calcium channel and/or an N-type calcium channel inhibitor, an agent for treating, preventing or improving a disease against which a P/Q-type calcium channel and/or an N-type calcium channel inhibitory action is efficacious, an agent for inhibiting the death of neural cells or for protecting cerebral neural cells. [0054] Additionally, the present invention provides use of the compound represented by the above formula (I), a salt thereof or a hydrate of them for producing an agent for treating, preventing or improving neural diseases or an analgesic. [0055] The neural disease is any one of disease selected from acute ischemic stroke, cerebral apoplexy, cerebral infarction, head trauma, cerebral neural cell death, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, cerebral circulation metabolic affection, cerebral dysfunction, pain, spasm, schizophrenia, migraine, epilepsy, manic-depression, neural degenerative diseases, cerebral ischemia, AIDS dementia complications, edema, anxiety disorder, diabetic neuropathy, cerebral vascular dementia and multiple sclerosis. [0056] The meanings of the symbols, terms and the like described in the specification of the present application are illustrated below, and the present invention is illustrated in detail. [0057] The structural formula of a compound happens to represent a fixed isomer for convenience in the specification of the present application, but the present invention includes all of geometrical isomers which occur in the structure of the compound, optical isomers based on an asymmetric carbon, stereo-isomers, the isomers of tautomers and the like, and a mixture of the isomer. The present invention is not limited to the indication of the formulae for convenience, and may be one of the isomers and a mixture thereof. Accordingly, in the compounds of the present invention, there may exist an optically active body and a racemic body which have an asymmetric carbon atom in the molecule, but they are not limited in the present invention, and both of them are included therein. Further, crystal polymorphism happens to exist, but is not similarly limited, and the crystal form may be either single or a mixture of crystal forms and may be a hydrate in addition to an anhydride. A so-called metabolite which occurs due to decomposition of the compounds according to the present invention in vivo is also included in the scope of claim for patent of the present invention. Continue reading about Nitrogen-containing cyclic compound and pharmaceutical composition containing the compound... Full patent description for Nitrogen-containing cyclic compound and pharmaceutical composition containing the compound Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Nitrogen-containing cyclic compound and pharmaceutical composition containing the compound patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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