Patents Assigned to Ono Pharmaceuticals Co., Ltd.
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Patent number: 5536736Abstract: We proposed a novel compound having an activity of PGI.sub.2 receptor agonist.A phenoxyacetic acid derivative of the formula ##STR1## A is --C(R.sup.1).dbd.N.about.OR.sup.2, --CH(R)NH--OR.sup.2, --COE, --SO.sub.2 E, --CH.sub.2 --NR.sup.3 --Y, --Z--NR.sup.3 --CONR.sup.4 R.sup.5, --CH.sub.2 --OR.sup.6, --CO.sub.2 R.sup.6, --CH.sub.2 --O.about.N.dbd.CR.sup.7 R.sup.8, --CH.sub.2 --O--NHCHR.sup.7 R.sup.8, substituted by imidazolyl(methyl), pyrazolylmethyl, oxazolyl(methyl), thioxazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolylmethyl;T is alkylene, alkenylene, etc.;D is --CO.sub.2 R.sup.10, --CONR.sup.11 R.sup.12 ;E is (substitution) amino, hydradino;Y is substituted (thio) carbonyl, substituted sulfonyl;Z is --CH.dbd.N--, --CH.sub.2 NR.sup.3 --;R.sup.1, R.sup.3, R.sup. -R.sup.13 is each H or alkyl, etc.;R.sup.2, R.sup.4 -R.sup.9 is each H, alkyl or alkyl substituted by phenyl or hetero ring, etc. and non-toxic salts thereof, non-toxic acid addition salts thereof, possess an agonistic on PGI.sub.Type: GrantFiled: August 19, 1994Date of Patent: July 16, 1996Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Nobuyuki Hamanaka, Kanji Takahashi, Hidekado Tokumoto
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Patent number: 5534536Abstract: Fused phenol compounds of the formula (I): ##STR1## (wherein R.sup.1 and R.sup.2 each, independently, is H, halogen, trifluoromethyl, cyano, (substituted) alkyl, alkoxy, cycloalkyl, COOH, COOR.sup.6 (in which R.sup.6 is C1-6 alkyl), alkenyl or R.sup.1 and R.sup.2, taken together, is --CH.dbd.CH--CH.dbd.CH--, when R.sup.1 and R.sup.2 are ortho to each other; A is alkylene, alkenylene, oxyalkylene or ##STR2## (in which m is 1-6); B is a monocyclic hetero ring containing a nitrogen atom; G is --OR.sup.3A or --NR.sup.3B R.sup.3C (in which R.sup.3A, R.sup.3B and R.sup.3C each, independently, is H, alkyl, acyl, or alkoxyalkyl); R.sup.4 and R.sup.5 each, independently, is H, alkyl, or R.sup.4, R.sup.5 together with the carbon atom to which they are attached represent C4-7 cycloalkyl; and n is 1-3; non-toxic salts thereof, non-toxic acid addition salts thereof, and hydrates thereof.The compounds of the formula (I) have inhibitory activities on TXA.sub.Type: GrantFiled: August 23, 1994Date of Patent: July 9, 1996Assignee: Ono Pharmaceuticals Co. Ltd.Inventors: Shuichi Ohuchida, Fumio Nambu, Masaaki Toda
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Patent number: 5525604Abstract: A 4-aminopyrimidine of the formula (I): ##STR1## wherein A is a bond, C1-4 alkylene or C1-4 oxyalkylene;Y is a bond, C1-4 alkylene, C1-4 alkyleneoxy, C1-4 alkoxyphenylene or phenyl(C1-4)alkylene;Z is a bond or vinylene;R1 is 4-15 membered heterocyclic ring containing one or two nitrogen atom;R2 is (i) 4-15 membered heterocyclic ring containing one or two nitrogen, one or two of oxygen or one sulfur atom,(ii) C4-15 carbocyclic ring,(iii) C1-4 alkoxy,(iv) hydroxy(C1-4 alkoxy) or(v) hydroxy;R3 is (i) 4-15 membered heterocyclic ring containing one or two nitrogen, one oxygen, one sulfur, or one nitrogen and one sulfur atom,(ii) C4-15 carbocyclic ring,(iii) formula:CH2.dbd.CH(X)--whereinX is halogen.(iv) hydrogen.l is 1 or 2.and some compounds are excluded.and acid addition salts thereof, salts thereof; have inhibitory effect on cGMP-PDE, or additionally on TXA2 synthetase.Type: GrantFiled: August 24, 1994Date of Patent: June 11, 1996Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Sung J. Lee, Yoshitaka Konishi, Orest T. Macina, Kigen Kondo, Dingwei T. Yu, Tamara A. Miskowski
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Patent number: 5525486Abstract: The present invention relates to (1) a process for constructing a cDNA library which has a selectivity for signal peptides, that makes it possible to efficiently find out an unknown and useful polypeptide and a high efficiency; and relates to (2) a novel polypeptide consisting of 89 amino acids (including a signal peptide) produced by a stroma cell line, which is useful as an agent for preventing or treating, for example, anemia, leukopenia or infections and the like, and DNAs encoding for said polypeptide.Type: GrantFiled: January 14, 1994Date of Patent: June 11, 1996Assignees: Tasuku Honjo, Ono Pharmaceutical Co., Ltd.Inventors: Tasuku Honjo, Kei Tashiro, Hideaki Tada
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Patent number: 5514713Abstract: Disclosed are amidinophenol derivatives of the formula (I) and acid-addition salts thereof (in which R.sup.1 and R.sup.2 are alkyl, alkoxy, acyl, halogen, nitro, benzoyl, COOR.sub.4 ; A is bond, alkylene, group of the formula (II); R.sup.3 is group of the formula (III), (IV)) ##STR1## Compounds of the formula (I) have inhibitory activities on phospholipase A.sub.2 and proteases (especially trypsin), and are useful for the prevention and/or the treatment of inflammatory diseases, allergic diseases, disseminated intravascular coagulation, pancreatitis, severity in pancreatitis and multiple organ failure.Type: GrantFiled: December 2, 1994Date of Patent: May 7, 1996Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Hisao Nakai, Koumei Kamiyasu, Masanori Kawamura
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Patent number: 5508450Abstract: Benzopyran derivatives which have an inhibitory effect on the Maillard reaction as well as an antioxidizing effect are described herein. These derivatives may be utilized in the treatment and/or prevention of diabetic complications such as, for example, coronary heart disease, peripheral circulatory insufficiency or failure, cerebrovascular hindrance, neurogenous diabetes, nephropathy, arteriosclerosis, arthrosclerosis, cataracts and retinopathy. Further, the derivatives may also be used in the treatment and/or prevention of diseases induced by aging and in the treatment and/or prevention of diseases caused by the formation of peroxidized fat.Type: GrantFiled: September 30, 1994Date of Patent: April 16, 1996Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Shuichi Ohuchida, Masaaki Toda, Tsumoru Miyamoto
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Patent number: 5506205Abstract: The present invention is related to a novel protein p140 polypeptide which is a key protein involved in the signal transmission system of insulin; method for preparation of it; DNA encoding the said polypeptide; vector comprising the DNA; host cells transformed with the vector; antibody against the polypeptide; pharmaceutical compositions containing the peptide or antibody; method for the prevention and/or treatment of diabetes, which is characterized by tyrosine phosphorylation of the said protein p140; agent for the prevention and/or treatment of diabetes, which is characterized by containing a compound which can tyrosine phosphorylate protein p140, as active ingredient and screening methods for the prevention and/or treatment agent.Tyrosine phosphorylation of protein p140 is an essential step in the induction of hypoglycemia by glucose uptake.Type: GrantFiled: November 23, 1994Date of Patent: April 9, 1996Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Hisao Tajima, Koichiro Kitagawa, Hiroyuki Ohno
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Patent number: 5494662Abstract: A stimulator for bone formation containing human interleukin 4 or an analogue thereof as an active ingredient. This stimulator is useful for the prevention and treatment of, for example, osteoporosis, osteogenesis imperfecta, injured bone and abnormality of dental and the improvement of metabolic abnormality of bone.Type: GrantFiled: April 21, 1993Date of Patent: February 27, 1996Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Ueno Kohji, Teruaki Katayama, Tsumoru Miyamoto
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Patent number: 5480998Abstract: An oxime derivative (I): ##STR1## that D ring and B bonding to D ring are (i)-(iv), wherein R.sup.1 is hydrogen, lower alkyl; R.sup.2 is hydrogen, alkyl, phenyl, cycloalkyl, monocyclic ring containing nitrogen, lower alkyl substituted by benzene ring or cycloalkyl, lower alkyl substituted by monocyclic ring containing nitrogen; R.sup.3 is alkyl, phenyl, cycloalkyl, monocyclic ring containing nitrogen, lower alkyl substituted by benzene ring or cycloalkyl, lower alkyl substituted by monocyclic ring containing nitrogen; e is 3-5, f is 1-3, p is 1-4, q is 1-2, r is 1-3; the position of the bond to D ring in (iii) and (iv) is a or b, and the ring in R.sup.2 and R.sup.3 may be substituted by lower alkyl, alkoxy, halogen, nitro, trihalomethyl; and salts thereof, possess an agonistic activity on PGl2 receptor, and therefore are useful for prevention and/or treatment of thrombosis, arteriosclerosis, ischemic heart diseases, gastric ulcer and hypertension.Type: GrantFiled: March 17, 1994Date of Patent: January 2, 1996Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Nobuyuki Hamanaka, Kanji Takahashi, Hidekado Tokumoto
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Patent number: 5470956Abstract: Polyclonal and monoclonal antibodies are obtained specific to mevalonic acid, having low cross-reactivity with mevalonic acid analogues, such as glutaric acid, 3-methylglutaric acid and 3-hydroxy-3-methylglutaric acid. The antibodies may be used for determination of mevalonic acid providing an immunoassay excellent in sensitivity, specificity and reproducibility.Type: GrantFiled: January 21, 1994Date of Patent: November 28, 1995Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Akio Hayashi, Makoto Hiramatsu, Nobuyuki Hamanaka
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Patent number: 5461045Abstract: A fused benzeneoxyacetic acid derivative of the formula: ##STR1## wherein ##STR2## is (i) ##STR3## (ii) ##STR4## (iii) ##STR5## or (iv) ##STR6## A is (i) ##STR7## or (ii) ##STR8## R.sup.1 is hydrogen or C.sub.1-4 alkyl; R.sup.2 is hydrogen, C.sub.1-6 alkyl or phenyl;R.sup.3 is(i) C.sub.1-15 alkyl,(ii) C.sub.1-8 alkyl substituted by one or two of benzene, C.sub.4-7 cycloalkane or 4-7 ring-membered monocyclic ring which contains one nitrogen atom or(iii) C.sub.10-15 condensed tricyclic ring;e is 3-5;f is 1-3;p is 0-4;q is 0-2;s is 0-3With the proviso that, ring(s) in R.sup.3 may be substituted by one to three of C.sub.1-4 alkyl, .sub.1-4 alkoxy, halogen atom, nitro or trihalomethyl. And, when D--B is the formula (iii) or (iv), --(CH2)p- or .dbd.CH--(CH2)s- is attached at the position of a or b on the ring.Type: GrantFiled: July 14, 1992Date of Patent: October 24, 1995Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Nobuyuki Hamanaka, Kanji Takahashi, Hidekado Tokumoto
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Patent number: 5459134Abstract: A novel (fused) benz(thio)amide of the general formula: ##STR1## or a non-toxic salt thereof, wherein R.sup.4 represents:(i) when B represents a closed ring, a group of the general formula: ##STR2## wherein U represents an oxygen atom or a sulfur atom; or (ii) when B represents a divalent group, a group of the general formula: ##STR3## wherein R.sup.5, R.sup.6, R.sup.7, R.sup.8, n, m, p and q are as defined in the specification, and exclusing certain compounds as defined in the specification, depending on whether A represents a single bond or a group. The compounds are useful for the prevention and/or treatment of diseases induced by leukotrienes, 5.alpha.-reductase, phospholipase and aldose reductase in mammals, especially human beings.Type: GrantFiled: October 21, 1994Date of Patent: October 17, 1995Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Masaaki Toda, Tsumoru Miyamoto, Yoshinobu Arai
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Patent number: 5457122Abstract: The phenylalkan(en)oic acids of the formula: ##STR1## as defined herein, possess an antagonistic activity on leukotriene B.sub.4.Type: GrantFiled: July 13, 1993Date of Patent: October 10, 1995Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Mitoshi Konno, Takahiko Nakae, Nobuyuki Hamanaka
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Patent number: 5446058Abstract: A novel (fused) benz(thio)amide of the general formula: ##STR1## or a non-toxic salt thereof, wherein A represents a single bond or a group as defined in the specification;B represents(i) a substituted or unsubstituted carbocyclic ring of 4 to 8 members being unreplaced or optionally having one, two or three carbon atom(s) replaced by oxygen, nitrogen and/or sulfur atom(s); or(ii) a divalent group of formula: ##STR2## T represents oxygen or sulfur; R.sup.1 represents a group of general formula: ##STR3## or (iv) a straight or branched alkyl, alkenyl or alkynyl group of from 1 to 20 carbon atom(s);R.sup.2 represents hydrogen or a straight or branched alkyl group of from 1 to 6 carbon atom(s);R.sup.' represents hydrogen, a halogen atom, a hydroxy group, a nitro group or a group --COOR.sup.7 ;R.sup.Type: GrantFiled: November 29, 1991Date of Patent: August 29, 1995Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Masaaki Toda, Tumoru Miyamoto, Yoshinobu Arai
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Patent number: 5439895Abstract: The compounds of the formula: ##STR1## wherein R.sup.1, Y, A, Z, CyB, R.sup.3, R.sup.4, n and m are described in the specification and claims.and acid addition salts thereof, salts thereof, and hydrates thereof; have inhibitory effect on cGMP-PDE, and additionally on TXA.sub.2 synthetase.Type: GrantFiled: November 19, 1993Date of Patent: August 8, 1995Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Sung J. Lee, Yoshitaka Konishi, Orest T. Macina, Kigen Kondo, Dingwei T. Yu
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Patent number: 5436233Abstract: The compounds of the formula: ##STR1## wherein R.sup.1, Y, A, R.sup.4, n, Z, CyB, R.sup.3, and m are defined in the specification.Type: GrantFiled: November 19, 1993Date of Patent: July 25, 1995Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Sung J. Lee, Yoshitaka Konishi, Orest T. Macina, Kigen Kondo, Dingwei T. Yu
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Patent number: 5432178Abstract: Amidinophenol derivatives of the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are (i) H, (ii) C1-4 alkyl, (iii) C1-4 alkoxy, (iv) C2-5 acyl, (v) halogen, (vi) NO.sub.2, (vii) benzoyl, (viii) COOR.sup.4 (in which R.sup.4 is C1-3 alkyl); A is bond, C1-4 alkylene, --C(R.sup.5).dbd.C(R.sup.6)-- (in which R.sup.5 and R.sup.6 are H or C1-4 alkyl; R.sup.3 is (i) CON(R.sup.7)(R.sup.8), (ii) CON(R.sup.9)--CH(R.sup.7)(R.sup.8) or (iii) ##STR2## in which ##STR3## is 4-7 membered, mono-cyclic hetero ring containing 1 or 2 N atom; R.sup.10 is H, C7-10 phenylalkyl or COOR.sup.13 (in which R.sup.13 is H, C1-4 alkyl or C7-10 phenylalkyl)); with the proviso that (i) both R.sup.7 and R.sup.8 do not represent hydrogen at the same time, and (ii) when at least one group in R.sup.7, R.sup.8 and R.sup.9 represents the group containing t-butyl ester, the other groups do not represent tile group containing carboxy; or an acid-addition salt thereof, have inhibitory activities on PLA.sub.Type: GrantFiled: September 16, 1993Date of Patent: July 11, 1995Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Hisao Nakai, Masanori Kawamura, Tsumoru Miyamoto
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Patent number: 5411974Abstract: Heterocyclic compounds of the general formula: ##STR1## wherein, Z represents methylene group or sulfur atom, R represents a general formula:G--E--D--B--A--.Type: GrantFiled: June 27, 1994Date of Patent: May 2, 1995Assignee: ONO Pharmaceutical Co., Ltd.Inventors: Masaaki Toda, Shuichi Ohuchida, Hiroyuki Ohno
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Patent number: 5403850Abstract: A derivative of general formula: ##STR1## wherein Y is --SO.sub.2 --or ##STR2## (i) R.sup.1 and R.sup.2, which may the same or different, each represent, (1) --H,(2) C1-16 alkyl or (3) the formula ##STR3## wherein X is single-bond, --SO.sub.2 --, C1-4 alkylene, C1-4 alkylene substituted by --COOH or ##STR4## is a pyridyl or pyrrolyl ring, n is 1.about.5, R.sup.4 is 1 --H or C1-8 alkyl, 2 C1-14 alkoxy 3 C1-6 alkylthio, 4 --OH, halogen, --NO.sub.2 or trihalomethyl, 5 the formula: --NR.sup.41 R.sup.42 wherein R.sup.41 and R.sup.42 each represents halogen or C1-4 alkyl, 6 tetrazole, 7 --SO.sub.3 H or --CH.sub.2 OH, 8 the formula:--SO.sub.2 NR.sup.41 R.sup.42 9 the formula: --Z.sup.41 --COOR.sup.43 wherein Z.sup.41 is single-bond C1-4 alkylene or C2-4 alkenylene, R.sup.43 is --H C1-4 alkyl or benzyl; or non-toxic salt or an acid addition salt thereof possess inhibitory activity on elastase, and therefore is useful for treating pulmonary emphysema, atherosclerosis and rheumatoid arthritis and the like.Type: GrantFiled: April 29, 1994Date of Patent: April 4, 1995Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Katsuhiro Imaki, Yoshinobu Arai, Tadao Okegawa
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Patent number: 5401760Abstract: Heterocyclic compounds of the general formula: ##STR1## R represents a general formula:G--E--D--B--A--G represents a carbocyclic or heterocyclic ring which is unsubstituted or substituted, L represents a group of general formula:--CO--COR.sup.2--CO--CH.sub.2 --COR.sup.2--CO--CF.sub.2 --COR.sup.2--CO--CO--NR.sup.5 R.sup.6or--CO--CH.sub.2 --CO--NR.sup.5 R.sup.6and non-toxic salt or hydrate thereof possess an inhibitory activity on propyl endopeptidase, and therefore usefull for prevention and/or treatment of amnesia.Type: GrantFiled: January 22, 1993Date of Patent: March 28, 1995Assignee: Ono Pharmaceutical Co., Ltd.Inventors: Masaaki Toda, Shuichi Ohuchida, Hiroyuki Ohno