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71. 发明专利

DE69128617D1 未知
公开(公告)号：DE69128617D1
公开(公告)日：1998-02-12
申请号：DE69128617
申请日：1991-02-05
申请人： SALK INST FOR BIOLOGICAL STUDI
发明人： RIVIER JEAN E F , RIVIER CATHERINE L , VALE WYLIE W JR , KOERBER STEVEN C , HAGLER ARNOLD T
IPC分类号： A61K38/24 , A61K38/00 , C07K1/04 , C07K1/113 , C07K7/23 , C07K14/575

72. 发明专利

AT96807T 未知
公开(公告)号：AT96807T
公开(公告)日：1993-11-15
申请号：AT84302558
申请日：1984-04-13
申请人： SALK INST FOR BIOLOGICAL STUDI
发明人： RIVIER JEAN E F , SPIESS JOACHIM , VALE WYLIE W JR
IPC分类号： C12N15/09 , A61K35/30 , A61K38/00 , A61K38/02 , A61K38/04 , A61K38/22 , A61P5/00 , A61P9/12 , C07K14/00 , C07K14/575 , C12N15/00 , C07K7/10 , A61K37/02
摘要： Rat Corticotropin Releasing Factor (rCRF) and the human counterpart thereof have the formula:… H-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-… Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-… Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-… Ser-Asn-Arg-Lys-Leu-Met-Glu-Ile-Ile-NH2.… Analogs are disclosed that are at least as potent. One which has been found to be particularly potent is:… H-Ser-Gln-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-… Phe-His-Leu-Leu-Arg-Glu-Met-Leu-Glu-Met-… Ala-Lys-Ala-Glu-Gln-Glu-Ala-Glu-Gln-Ala-… Ala-Leu-Asn-Arg-Leu-Leu-Leu-Glu-Glu-Ala-NH2.… These analogs or pharmaceutically or veterinarily acceptable salts thereof, dispersed in a pharmaceutically or veterinarily acceptable liquid or solid carrier, can be administered to mammals, including humans, to achieve a substantial elevation of ACTH, beta -endorphin, beta -lipotropin, other products of the pro-opiomelanocortin gene and corticosterone levels and/or a lowering of blood pressure over an extended period of time. They may also be used as stimulants to elevate mood and improve memory and learning, as well as diagnostically. … In the analogs, one or more of the first three N-terminal residues may be deleted or may be substituted by a peptide up to 10 amino acids long and/or by an acylating agent containing up to 7 carbon atoms. A number of other substitutions may also be made throughout the chain.

73. 发明专利

CA1312704C GRF ANALOGS VII 未知
公开(公告)号：CA1312704C
公开(公告)日：1993-01-12
申请号：CA567405
申请日：1988-05-20
申请人： SALK INST FOR BIOLOGICAL STUDI
发明人： RIVIER JEAN E F , VALE WYLIE W JR , RIVIER CATHERINE L
IPC分类号： A61K38/00 , A61K38/04 , A61K38/25 , A61P5/00 , A61P15/00 , A61P35/00 , A61P43/00 , C07K14/00 , C07K14/575 , C07K14/60 , C07K14/61 , C07K7/10 , A61K37/02
摘要： GRF ANALOGS VII The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in animals, including humans, which have resistance to enzymatic degradation in the body, and which have the sequence: R44 is a natural amino acid; Q1-Q4 are either H or CaMe, provided however that any or all of the residues between R30 and R44, inclusive, may be deleted, and provided also that at least one of Q1Q4 is CaMe and/or R8 is Lys or Arg and/or R21 is D-Lys or D-Arg. These peptides as well as their nontoxic salts may also be used diagnostically.

74. 发明专利

NO167866B 未知
公开(公告)号：NO167866B
公开(公告)日：1991-09-09
申请号：NO842148
申请日：1984-05-30
申请人： SALK INST FOR BIOLOGICAL STUDI
发明人： RIVIER JEAN E F , SPIESS JOACHIM , VALE WYLIE W JR
IPC分类号： A61K38/00 , A23K1/16 , A61K38/04 , A61K38/07 , A61K38/25 , C07C20060101 , C07K1/06 , C07K14/00 , C07K14/575 , C07K14/60 , C07K14/61 , C07K7/10
摘要： Two surprisingly active fragments of human pancreatic GRF have been synthesized, along with an analog which exhibits good biological activity. The synthetic peptides are extremely potent in stimulating the release of pituitary GH in humans and nonhuman animals and have the general formula:… H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-R15-Gln-Leu-Ser-Ala-Ar g-Lys-Leu-Leu-Gln-Asp-lle-Met-Ser-Arg-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-R40-Y wherein R15 is Gly or D-Ala, R40 is Ala or des-R40 and Y signifies the carboxyl moiety of the amino acid residue at the C-terminal and is the radical -COOR1, -CR1O, -CONHNHR1, -CON(R1)(R2) or -CH2OR1, with R1 and R2 being lower alkyl or hydrogen. The two fragments include the 29 or 32 N-terminal residues and are each amidated at the C-terminus. These peptides, as well as nontoxic salts thereof, may be administered therapeutically to animals, including humans.

75. 发明专利

CA1247605A CRF ANALOGS 未知
公开(公告)号：CA1247605A
公开(公告)日：1988-12-28
申请号：CA477389
申请日：1985-03-25
申请人： SALK INST FOR BIOLOGICAL STUDI
发明人： VALE WYLIE W JR , RIVIER JEAN E F
IPC分类号： A61K38/00 , C07K14/575 , C07K7/38
摘要： CRF ANALOGS Analogs of rCRF and oCRF are disclosed that can be administered to achieve a substantial elevation of ACTH, .beta.-endorphin, B-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone levels and/or a lowering of blood pressure over an extended period of time. One analog which has been found to be particularly potent is: . In the analogs, one or more of the first five N-terminal residues may be deleted or may be substituted by a peptide up to 10 amino acids long and/or by an acylating agent containing up to 7 carbon atoms. A number of other substitutions may also be made throughout the chain. These analogs or pharmaceutically or veterinarily acceptable salts thereof, dispersed in a pharmaceutically or veterinarily acceptable liquid or solid carrier, can be administered to mammals, including humans. These analogs may also be used as stimulants to elevate mood and improve memory and learning, as well as diagnostically.

76. 发明专利

CA1186302A LRF ANTAGONISTS 未知
公开(公告)号：CA1186302A
公开(公告)日：1985-04-30
申请号：CA375536
申请日：1981-04-15
申请人： SALK INST FOR BIOLOGICAL STUDI
发明人： VALE WYLIE W JR , RIVIER JEAN E F
IPC分类号： C07C103/52
摘要： LRF ANTAGONISTS Peptides which inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. The peptides have the structure: X-R1-R2-R3-Ser-Tyr-R4-R5-Arg-Pro-R6 wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R1 is dehydro Pro, dehydro D-Pro, Thz or D-Thz; R2 is D-Phe, D-His, D-Trp, Trp, Cl-D-Phe, dichloro-D-Phe, CF3-D-Phe, F-D-Phe, difluoro-D-Phe, AcNH-D-Phe, NO2-D-Phe, dinitro-D-Phe, Br-D-Phe, dibromo-D-Phe, CH3S-D-Phe, OCH3-D-Phe or CH3-D-Phe; R3 is D-Trp, Trp, D-Phe or D-His; R4 is Gly or a D-isomer amino acid; R5 is Leu or N.alpha.Me-Leu; and R6 is Gly-NH2 or NHCH2CH3.

77. 发明专利

NO842148L 未知
公开(公告)号：NO842148L
公开(公告)日：1984-05-30
申请号：NO842148
申请日：1984-05-30
申请人： SALK INST FOR BIOLOGICAL STUDI
发明人： RIVIER JEAN E F , SPIESS JOACHIM , VALE WYLIE W JR
IPC分类号： A61K38/00 , A23K1/16 , A61K38/04 , A61K38/07 , A61K38/25 , C07C20060101 , C07K1/06 , C07K14/00 , C07K14/575 , C07K14/60 , C07K14/61 , C07C
摘要： Two surprisingly active fragments of human pancreatic GRF have been synthesized, along with an analog which exhibits good biological activity. The synthetic peptides are extremely potent in stimulating the release of pituitary GH in humans and nonhuman animals and have the general formula:… H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-R15-Gln-Leu-Ser-Ala-Ar g-Lys-Leu-Leu-Gln-Asp-lle-Met-Ser-Arg-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-R40-Y wherein R15 is Gly or D-Ala, R40 is Ala or des-R40 and Y signifies the carboxyl moiety of the amino acid residue at the C-terminal and is the radical -COOR1, -CR1O, -CONHNHR1, -CON(R1)(R2) or -CH2OR1, with R1 and R2 being lower alkyl or hydrogen. The two fragments include the 29 or 32 N-terminal residues and are each amidated at the C-terminus. These peptides, as well as nontoxic salts thereof, may be administered therapeutically to animals, including humans.

78. 发明专利

NO842148A 未知
公开(公告)号：NO842148A
公开(公告)日：1984-05-30
申请号：NO842148
申请日：1984-05-30
申请人： SALK INST FOR BIOLOGICAL STUDI
发明人： RIVIER JEAN E F , SPIESS JOACHIM , VALE WYLIE W JR
IPC分类号： A61K38/00 , A23K1/16 , A61K38/04 , A61K38/07 , A61K38/25 , C07C20060101 , C07K1/06 , C07K14/00 , C07K14/575 , C07K14/60 , C07K14/61 , C07C
CPC分类号： C07K14/60 , A61K38/00 , Y10S530/845 , Y10S930/12

79. 发明专利

CS228924B2 METHOD OF PREPARING PEPTIDES INHIBITING THE RELEASE OF GONADOTROPINE FROM MAMMALIAN HYPOPHYSIS 未知
公开(公告)号：CS228924B2
公开(公告)日：1984-05-14
申请号：CS283282
申请日：1982-04-20
申请人： SALK INST FOR BIOLOGICAL STUDI
发明人： RIVIER JEAN E F , VALE WYLIE W JR
IPC分类号： C07K14/575 , A61K38/00 , A61K38/04 , A61P43/00 , C07C231/00 , C07K1/113 , C07K7/06 , C07K7/16 , C07K7/23 , C07C103/52
摘要： Peptides which inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. The peptides have the structure. X-R1-R2-R3-Ser-Tyr-R4-R5-Arg-Pro-R6 wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R1 is dehydro Pro or dehydro D-Pro; R2 is D-Phe, Cl-D-Phe, dichloro-D-Phe, CF3-D-Phe, F-D-Phe, difluoro-D-Phe, AcNH-D-Phe, NO2-D-Phe, dinitro-D-Phe, Br-D-Phe, dibromo-D-Phe, CH3-S-D-Phe, OCH3-D-Phe or CH3-D-Phe; R3 is D-Trp or B-D-NAL; R4 is a D-isomer amino acid and preferably B-D-NAL; R5 is Leu or N Me-Leu; and R6 is Gly-NH2 or NHCH2CH3; provided however that either R3 or R4 is B-D-NAL.

80. 发明专利

CA1154758A WATER-SOLUBLE PEPTIDES AFFECTING GONADAL FUNCTION 未知
公开(公告)号：CA1154758A
公开(公告)日：1983-10-04
申请号：CA352676
申请日：1980-05-26
申请人： SALK INST FOR BIOLOGICAL STUDI
发明人： RIVIER JEAN E F , VALE WYLIE W JR
IPC分类号： A61K38/04 , A61K38/00 , A61P5/00 , A61P15/00 , C07K7/23 , C07K14/575 , C07C103/52
摘要： WATER-SOLUBLE PEPTIDES AFFECTING GONADAL FUNCTION ¢im-Bzl D-His6!LRF and ¢D-His (im-Bzl), Pro9-NEt! LRF exhibit hydrophillicity comparable to that of LRF and act as superagonists exhibiting potencies, respectively, about 12 and more than 200 times that of LRF. The peptides or their nontoxic salts can be administered by intravenous, subcutaneous, sublingual, oral, intravaginal, intranasal or rectal routes. The peptides can be used to regulate fertility in male and female mammals, including human beings.

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