公开(公告)号：US5003011A

公开(公告)日：1991-03-26

申请号：US421245

申请日：1989-10-13

申请人： David H. Coy ,  Jacques-Pierre Moreau

发明人： David H. Coy ,  Jacques-Pierre Moreau

IPC分类号： A61K38/00 ,  C07K7/06 ,  C07K7/23

CPC分类号： C07K7/06 ,  C07K7/23 ,  A61K38/00 ,  Y10S514/80 ,  Y10S514/885

摘要： A decapeptide of the formula:N-Ac-A.sup.1 -A.sup.2 -A.sup.3 -SER.sup.4 -A.sup.5 -A.sup.6 -A.sup.7 -A.sup.8 -A.sup.9 -A.sup.10,wherein each A.sup.1, A.sup.2, and A.sup.3, independently, is D-.beta.-Nal, D-p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, OH, or C.sub.1-3 alkyl); A.sup.5 is p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, OH, or C.sub.1-3 alkyl); A.sup.6 is D-Lys, D-Arg, .beta.-Nal, D-.beta.-Nal, D-Trp, D-p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, or C.sub.1-3 alkyl) or D-lys-.epsilon.-NH-R (where R is H, a branched or straight chain or cyclo C.sub.1 -C.sub.10 alkyl group, or an aryl group); A.sup.7 is p-X-Phe (where X is halogen, H, NH.sub.2, NO.sub.2, OH, C.sub.2 F.sub.5, or C.sub.1-3 alkyl), cyclohexyala, or Trp; A.sup.8 is Arg, Lys, or Lys-.epsilon.-NH-R (where R is H, a branched or straight chain or cyclo C.sub.1 -C.sub.10 alkyl group, or an aryl croup); A.sup.9 is Pro; and A.sup.10 is D-Ala-NH.sub.2, Gly-NH.sub.2, D-Ser, or D-Ser-NH.sub.2 ; provided that at least one of A.sup.2 or A.sup.3 must be D-Phe or D-Tyr; and further provided that one or both of A.sup.6 and A.sup.8 must be the following: A.sup.6 must be D-Lys-.epsilon.-NH-R (where R is H, a branched or straight chain or cyclo C.sub.1 -C.sub.10 alkyl group, or an aryl group); A.sup.8 must be Lys-.epsilon.-NH-R (where R is H, a branched or straight chain or cyclo C.sub.1 -C.sub.10 alkyl group, or an aryl group), or a pharmaceuticaly acceptable salt thereof.

摘要翻译： 具有下式的十肽：N-Ac-A1-A2-A3-SER4-A5-A6-A7-A8-A9-A10，其中每个A1，A2和A3独立地是D-β-Nal，DpX- Phe（其中X为卤素，H，NH 2，NO 2，OH或C 1-3烷基）; A5是p-X-Phe（其中X是卤素，H，NH 2，NO 2，OH或C 1-3烷基）; A6是D-Lys，D-Arg，β-Nal，D-β-Nal，D-Trp，DpX-Phe（其中X是卤素，H，NH 2，NO 2或C 1-3烷基）或D-lys- ε--NH-R（其中R是H，支链或直链或环C 1 -C 10烷基或芳基）; A7是p-X-Phe（其中X是卤素，H，NH2，NO2，OH，C2F5或C1-3烷基），环己烯或Trp; A8是Arg，Lys或Lys-ε--NH-R（其中R是H，支链或直链或环C1-C10烷基或芳基）。 A9是Pro A10为D-Ala-NH2，Gly-NH2，D-Ser或D-Ser-NH2; 条件是A2或A3中的至少一个必须是D-Phe或D-Tyr; 并且进一步规定A6和A8之一或两者必须为：A6必须为D-Lys-ε--NH-R（其中R为H，支链或直链或环C1-C10烷基或芳基 组）; A8必须是Lys-ε--NH-R（其中R是H，支链或直链或环C1-C10烷基或芳基）或其药学上可接受的盐。

公开(公告)号：US4871717A

公开(公告)日：1989-10-03

申请号：US1245

申请日：1987-01-07

申请人： David H. Coy ,  William A. Murphy

发明人： David H. Coy ,  William A. Murphy

IPC分类号： A61K38/00 ,  A61K38/04 ,  A61P1/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/08 ,  A61P25/04 ,  A61P35/00 ,  A61P39/02 ,  A61P43/00 ,  C07K7/06 ,  C07K14/575 ,  C07K14/655

CPC分类号： C07K14/6555 ,  A61K38/00 ,  Y10S930/16

摘要： Heptapeptide analogs of somatastatin which inhibit secretion of growth hormone.

摘要翻译： 抑制生长激素分泌的生长抑素的肽类似物。

公开(公告)号：US4431635A

公开(公告)日：1984-02-14

申请号：US341137

申请日：1982-01-20

申请人： David H. Coy ,  Andrew V. Shally

发明人： David H. Coy ,  Andrew V. Shally

IPC分类号： A61K38/00 ,  C07K7/23 ,  C07C103/52

CPC分类号： C07K7/23 ,  A61K38/00 ,  Y10S514/80 ,  Y10S930/13

摘要： Disclosed herein are peptide analogs of the luteinizing hormone releasing hormone (LH-RH) which are potent antagonists of LHRH. The analogs differ in structure from LH-RH by having different amino acid residues at positions 1, 2 and 6, and optionally at positions 3 and 10. Methods for preparing and using these analogs are described.

摘要翻译： 本文公开了作为LHRH的有效拮抗剂的黄体生成激素释放激素（LH-RH）的肽类似物。 类似物在结构上与LH-RH的不同之处在于在1,2和6位以及任选地在3和10位具有不同的氨基酸残基。描述了制备和使用这些类似物的方法。

公开(公告)号：US4328134A

公开(公告)日：1982-05-04

申请号：US147112

申请日：1980-05-06

申请人： Andrew V. Schally ,  David H. Coy

发明人： Andrew V. Schally ,  David H. Coy

IPC分类号： C07K5/08 ,  A61K38/00 ,  A61P1/00 ,  A61P25/00 ,  C07K5/097 ,  C08L37/00 ,  C07C103/52

CPC分类号： C07K5/0825

摘要： There are disclosed peptides of the formula A-B-C and pharmaceutically acceptable salts thereof, in which A is selected from the group consisting of L-pyroglutamyl, D-pyroglutamyl, and L-homo-pyroglutamyl; B is selected from the group consisting of L-histidyl, L-3'-methylhistidyl, D-histidyl, L-phenylalanyl, L-p-aminophenylalanyl, and L-.beta.-(pyrazolyl-1)alanyl; and C is selected from the group consisting of glycine and lower alkyl esters thereof, glycinamide and lower alkyl amides thereof, 2-amino-1-hydroxyethyl, D-alanine, L-.beta.-(2-thienyl)-alanine, and NHR.sup.1 in which R.sup.1 is lower alkyl, with the proviso that C may not be glycine or glycinamide when A is L-pyroglutamyl and B is L-histidyl.The compounds have anorexigenic properties, inhibit excessive gastric and pancreatic secretion, and cause activation in the CNS. Methods for their preparation and use are also disclosed.

摘要翻译： 公开了式A-B-C的肽及其药学上可接受的盐，其中A选自L-焦谷氨酰基，D-焦谷氨酰和L-高 - 焦谷氨酰; B选自L-组氨酰基，L-3'-甲基组氨酸，D-组氨酰基，L-苯丙氨酰基，L-对氨基苯丙氨酰和L-β-（吡唑基-1）丙氨酰基; 和C选自甘氨酸及其低级烷基酯，甘氨酰胺及其低级烷基酰胺，2-氨基-1-羟乙基，D-丙氨酸，L-β-（2-噻吩基） - 丙氨酸和NHR1 其中R1为低级烷基，条件是当A为L-焦谷氨酰基且B为L-组氨酰基时，C不为甘氨酸或甘氨酰胺。 这些化合物具有厌食性，抑制胃和胰腺分泌过多，并引起CNS中的活化。 还公开了其制备和使用方法。

公开(公告)号：US4317815A

公开(公告)日：1982-03-02

申请号：US155249

申请日：1980-06-02

申请人： David H. Coy ,  Andrew V. Schally

发明人： David H. Coy ,  Andrew V. Schally

IPC分类号： A61K38/00 ,  C07K7/23 ,  A61K37/00 ,  C07C103/52

CPC分类号： C07K7/23 ,  A61K38/00 ,  Y10S514/80 ,  Y10S930/13

摘要： Disclosed herein are peptide analogs of the luteinizing hormone releasing hormone (LH-RH) which are potent antagonist of LHRH. The analogs differ in structure from LH-RH by having different amino acid residues at positions 1, 2 and 6, and optionally at positions 3 and 10. Methods for preparing and using these analogs are described.

摘要翻译： 本文公开了作为LHRH的有效拮抗剂的黄体生成激素释放激素（LH-RH）的肽类似物。 类似物在结构上与LH-RH的不同之处在于在1,2和6位以及任选地在3和10位具有不同的氨基酸残基。描述了制备和使用这些类似物的方法。

公开(公告)号：US4312857A

公开(公告)日：1982-01-26

申请号：US807129

申请日：1977-06-16

申请人： David H. Coy ,  Abba J. Kastin

发明人： David H. Coy ,  Abba J. Kastin

IPC分类号： C07K14/675 ,  A61K37/00 ,  C07C103/52

CPC分类号： C07K14/6755 ,  Y10S514/809 ,  Y10S930/28

摘要： Novel hentriacontapeptides having the following amino acid sequence:H-Tyr-X-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu-Ywherein X is a chiral residue of a D-amino acid selected from the group consisting of D-alanine, D-leucine, D-isoleucine, D-valine, D-phenylalanine, D-tyrosine, D-tryptophan, D-serine, D-threonine, D-methionine, D-glutamic acid, D-glutamine, D-aspartic acid, D-asparagine, D-lysine, D-proline, D-histidine or D-arginine; Y is selected from the group consisting of hydroxy, amino, loweralkylamino, diloweralkylamino and lower alkoxy; and the pharmaceutically acceptable salts thereof; intermediates useful in making the novel compounds and pharmaceutical compositions and methods employing the novel compounds.

摘要翻译： 具有以下氨基酸序列的新型三钠肽：H-Tyr-X-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Ph e-Lys- Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu-Y其中X是D-氨基酸的手性残基，其选自D-丙氨酸，D-亮氨酸 ，D-异亮氨酸，D-缬氨酸，D-苯丙氨酸，D-酪氨酸，D-色氨酸，D-丝氨酸，D-苏氨酸，D-甲硫氨酸，D-谷氨酸，D-谷氨酰胺，D-天冬氨酸，D-天冬酰胺 D-赖氨酸，D-脯氨酸，D-组氨酸或D-精氨酸; Y选自羟基，氨基，低级烷基氨基，二低级烷基氨基和低级烷氧基; 及其药学上可接受的盐; 可用于制备新化合物的中间体和使用该新化合物的药物组合物和方法。

公开(公告)号：US4180501A

公开(公告)日：1979-12-25

申请号：US915981

申请日：1978-06-16

申请人： David H. Coy ,  Abba J. Kastin

发明人： David H. Coy ,  Abba J. Kastin

IPC分类号： A61K38/00 ,  C07K5/107 ,  C07K14/67 ,  C07K14/70 ,  C07C103/52 ,  A61K37/00

CPC分类号： C07K14/672 ,  C07K14/702 ,  C07K5/1016 ,  A61K38/00 ,  Y10S514/809 ,  Y10S930/12

摘要： Bis-(polypeptide) derivatives represented by the formulae: ##STR1## wherein: X is glycine or a chiral residue of a D-amino acid selected from the group consisting of D-alanine, D-leucine, D-isoleucine, D-valine, D-norvaline, D-phenylalanine, D-tyrosine, D-tryptophan, D-serine, D-threonine, D-methionine, D-glutamic acid, D-glutamine, D-aspartic acid, D-asparagine, D-lysine, D-proline, D-histidine and D-arginine; Y a residue of methionine or leucine and Z is selected from the group consisting of hydroxy, amino, loweralkylamine, diloweralkylamino and loweralkoxy; each R.sub.1 is hydrogen or fluorine and the pharmaceutically acceptable salts thereof; intermediates useful in making the novel pentapeptides and pharmaceutical compositions and methods employing them.

摘要翻译： 由下式表示的双（多肽）衍生物：其中：X是甘氨酸或D-氨基酸的手性残基，其选自D-丙氨酸，D D-亮氨酸，D-异亮氨酸，D-缬氨酸，D-正缬氨酸，D-苯丙氨酸，D-酪氨酸，D-色氨酸，D-丝氨酸，D-苏氨酸，D-甲硫氨酸，D-谷氨酸，D-谷氨酰胺， 天冬氨酸，D-天冬酰胺，D-赖氨酸，D-脯氨酸，D-组氨酸和D-精氨酸; Y是甲硫氨酸或亮氨酸的残基，Z选自羟基，氨基，低级烷基胺，二低级烷基氨基和低级烷氧基; 每个R 1是氢或氟及其药学上可接受的盐; 可用于制备新型五肽的中间体和使用它们的药物组合物和方法。

公开(公告)号：US4127539A

公开(公告)日：1978-11-28

申请号：US807214

申请日：1977-06-16

申请人： David H. Coy ,  Abba J. Kastin

发明人： David H. Coy ,  Abba J. Kastin

IPC分类号： A61K38/00 ,  C07K14/675 ,  C08L37/00 ,  A61K37/00 ,  C07C103/52

CPC分类号： C07K14/6755 ,  A61K38/00 ,  Y10S514/809 ,  Y10S930/12 ,  Y10S930/28

摘要： Novel hexacosapeptides having the following amino acid sequenceH-Tyr-X-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Ywherein: X is a chiral residue of a D-amino acid selected from the group consisting of D-alanine, D-leucine, D-isoleucine, D-valine, D-phenylalanine, D-tyrosine, D-tryptophan, D-serine, D-threonine, D-methionine, D-glutamic acid, D-glutamine, D-proline D-aspartic acid, D-asparagine, D-lysine, D-arginine and D-histadine; and Y is selected from the group consisting of hydroxy, amino, loweralkylamino, diloweralkylamino and lower alkoxy; and the pharmaceutically acceptable salts thereof; intermediates useful in making the novel compounds; and pharmaceutical compositions and methods employing the novel compounds.

摘要翻译： 具有以下氨基酸序列H-Tyr-X-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Ph e-Lys-Asn的新型六肽 -Ala-Ile-Ile-Lys-Asn-Ala-Y其中：X是D-氨基酸的手性残基，其选自D-丙氨酸，D-亮氨酸，D-异亮氨酸，D-缬氨酸，D D-苯丙氨酸，D-酪氨酸，D-色氨酸，D-丝氨酸，D-苏氨酸，D-甲硫氨酸，D-谷氨酸，D-谷氨酰胺，D-脯氨酸D-天冬氨酸，D-天冬酰胺，D-赖氨酸， 精氨酸和D-组氨酸; Y选自羟基，氨基，低级烷基氨基，二低级烷基氨基和低级烷氧基; 及其药学上可接受的盐; 用于制备新型化合物的中间体; 以及使用该新化合物的药物组合物和方法。

公开(公告)号：US4127534A

公开(公告)日：1978-11-28

申请号：US807208

申请日：1977-06-16

申请人： David H. Coy ,  Abba J. Kastin

发明人： David H. Coy ,  Abba J. Kastin

IPC分类号： C07K5/087 ,  C08L37/00 ,  A61K37/00 ,  C07C103/52

CPC分类号： C07K5/0812 ,  Y10S514/809

摘要： Novel tripeptides having the following amino acid sequenceH-Tyr-X-Gly-Ywherein: X is a chiral residue of a D-amino acid selected from the group consisting of D-alanine, D-leucine, D-isoleucine, D-valine, D-phenylalanine, D-tyrosine, D-tryptophan, D-serine, D-threonine, D-methionine, D-glutamic acid, D-glutamine, D-proline D-aspartic acid, D-asparagine, D-lysine, D-arginine and D-histidine; and Y is selected from the group consisting of hydroxy, amino, loweralkylamino, diloweralkylamino and lower alkoxy; and the pharmaceutically acceptable salts thereof; intermediates useful in making the novel compounds; and pharmaceutical compositions and methods employing the novel compounds.

摘要翻译： 具有以下氨基酸序列H-Tyr-X-Gly-Y的新型三肽，其中：X是D-氨基酸的手性残基，其选自D-丙氨酸，D-亮氨酸，D-异亮氨酸，D- 缬氨酸，D-苯丙氨酸，D-酪氨酸，D-色氨酸，D-丝氨酸，D-苏氨酸，D-甲硫氨酸，D-谷氨酸，D-谷氨酰胺，D-脯氨酸D-天冬氨酸，D-天冬酰胺，D-赖氨酸 ，D-精氨酸和D-组氨酸; Y选自羟基，氨基，低级烷基氨基，二低级烷基氨基和低级烷氧基; 及其药学上可接受的盐; 用于制备新型化合物的中间体; 以及使用该新化合物的药物组合物和方法。

公开(公告)号：US4127533A

公开(公告)日：1978-11-28

申请号：US807207

申请日：1977-06-16

申请人： David H. Coy ,  Abba J. Kastin

发明人： David H. Coy ,  Abba J. Kastin

IPC分类号： A61K38/00 ,  C07K14/67 ,  C08L37/00 ,  C07C103/52

CPC分类号： C07K14/672 ,  A61K38/00 ,  Y10S514/809 ,  Y10S930/12 ,  Y10S930/28

摘要： Novel octapeptides having the following amino acid sequence:H-Tyr-X-Gly-Phe-Met-Thr-Ser-Glu-Ywherein: X is a chiral residue of a D-amino acid selected from the group consisting of D-alanine, D-leucine, D-isoleucine, D-valine, D-phenylalanine, D-tyrosine, D-tryptophan, D-serine, D-threonine, D-methionine, D-glutamic acid, D-glutamine, D-proline D-aspartic acid, D-asparagine, D-lysine, D-arginine and D-histidine; and Y is selected from the group consisting of hydroxy, amino, loweralkylamino, diloweralkylamino and lower alkoxy; and the pharmaceutically acceptable salts thereof; intermediates useful in making the novel compounds; the pharmaceutical compositions and methods employing the novel compounds.

摘要翻译： 具有以下氨基酸序列的新型八肽：