公开(公告)号：US4244947A

公开(公告)日：1981-01-13

申请号：US66258

申请日：1979-08-13

申请人： Nedumparampil A. Abraham ,  Francesco Bellini ,  Hans U. Immer ,  Marvin M. Kobric

发明人： Nedumparampil A. Abraham ,  Francesco Bellini ,  Hans U. Immer ,  Marvin M. Kobric

IPC分类号： A61K38/00 ,  C07K5/11 ,  C07K14/655 ,  A61K37/00 ,  C07C103/52

CPC分类号： C07K14/6555 ,  C07K5/1019 ,  A61K38/00 ,  Y10S514/806 ,  Y10S930/16

摘要： Peptides of formula I ##STR1## in which X is (CH.sub.2).sub.2, S--CH.sub.2 or CH.sub.2 --S or a therapeutically acceptable acid addition salt thereof are disclosed. The peptides of formula I are useful as agents for the treatment of acromegaly and the management of diabetes in a mammal. Compositions and methods for the preparation of the peptides of formula I are also disclosed.

摘要翻译： 公开了其中X是（CH 2）2，S-CH 2或CH 2 -S或其治疗上可接受的酸加成盐的式I的肽（I）。 式I的肽可用作治疗肢端肥大症和哺乳动物中糖尿病的治疗剂。 还公开了制备式I肽的组合物和方法。

公开(公告)号：US4216209A

公开(公告)日：1980-08-05

申请号：US21737

申请日：1979-03-19

申请人： Francesco Bellini ,  Hans U. Immer

发明人： Francesco Bellini ,  Hans U. Immer

IPC分类号： C07K5/06 ,  C07K5/078 ,  C07K5/097 ,  A61K37/00 ,  C07C103/52

CPC分类号： C07K5/06165 ,  C07K5/06069 ,  C07K5/0823 ,  Y10S530/80

摘要： Compounds of the formula HSCH.sub.2 CHR.sup.1 CO--Pro--R.sup.2 --R.sup.3 --OH in which R.sup.1 is hydrogen or lower alkyl, R.sup.2 is an amino acid residue exclusive of prolyl and R.sup.3 is an amino acid residue exclusive of glutamyl are useful for alleviating angiotensin related hypertension.

摘要翻译： R 1为氢或低级烷基的式HSCH2CHR1CO-Pro-R2-R3-OH的化合物，R2为不含脯氨酰基的氨基酸残基，R3为不含谷氨酰基的氨基酸残基，可用于缓解血管紧张素相关的高血压。

公开(公告)号：US4301066A

公开(公告)日：1981-11-17

申请号：US147884

申请日：1980-05-08

申请人： Francesco Bellini ,  Hans U. Immer

发明人： Francesco Bellini ,  Hans U. Immer

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

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

摘要： Herein is described a process for preparing the decapeptide Pry-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH.sub.2 ([D-Trp.sup.6 ]-LH-RH) by coupling Pyr-His-Trp-NHNH.sub.2 with H-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH.sub.2. [D-Trp.sup.6 ]-LH-RH had been established to be an efficient agent for causing release of lutenizing hormone and follicle-stimulating hormone in mammals.

摘要翻译： 本文描述了通过偶联Pyr-His-Trp（[D-Trp6] -LH-RH）制备十肽Pry-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH 2 -NHNH 2与H-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH 2。 [D-Trp6] -LH-RH已被确定为在哺乳动物中引起促黄体激素和促卵泡激素释放的有效药物。

公开(公告)号：US4159980A

公开(公告)日：1979-07-03

申请号：US456343

申请日：1974-03-29

申请人： Hans U. Immer ,  Verner R. Nelson ,  Manfred K. Gotz

发明人： Hans U. Immer ,  Verner R. Nelson ,  Manfred K. Gotz

IPC分类号： A61K38/00 ,  C07K5/097 ,  C07C103/52

CPC分类号： C07K5/0821 ,  A61K38/00 ,  Y10S514/80 ,  Y10S930/13

摘要： A process for preparing the LH- and FSH-releasing hormone of the formula Ih-- pyr-- His-- Trp-- Ser-- Tyr-- Gly-- Leu-- Arg-- Pro-- Gly-- NH.sub.2which comprises the following steps: Condensing N-(5-oxo-L-prolyl)-L-histidine hydrazide by means of the azide method with L-tryptophan benzyl ester and treating the resulting compound with hydrazine hydrate to obtain N-[N-(5-oxo-L-prolyl)-L-histidyl]-L-tryptophan hydrazide (II); treating N-[O-benzyl-N-carboxy-L-tyrosyl]glycine N-benzyl ester with ethyl chloroformate to obtain the corresponding mixed anhydride which is reacted with t-butyl carbazate to obtain the corresponding 2-carboxyhydrazide t-butyl ester which is hydrogenolyzed to N-L-tyrosylglycine 2-carboxyhydrazide t-butyl ester, and condensing the latter with N-carboxy-L-seryl N-benzyl ester 2,4-dinitrophenyl ester followed by hydrogenolysis of the reaction product to obtain N-(N-L-seryl-L-tyrosyl)glycine 2-carboxyhydrazide t-butyl ester (III); condensing N-carboxy-L-proline N-benzyl ester with glycine ethyl ester in the presence of dicyclohexylcarbodiimide, treating the resulting product with ammonia and then hydrogenolyzing, to obtain 2-[(L-prolyl)amino]acetamide, which is condensed with N-carboxy-N.sup.G -nitro-L-arginine N-t-butyl ester in the presence of dicyclohexylcarbodiimide and N-hydroxysuccinimide to obtain N-[N-(N-carboxy-N.sup.G -nitro-L-arginyl)-L-prolyl)]glycinamide N-t-butyl ester (IV); or alternatively condensing L-proline methyl ester with N-carboxy-N.sup.G -nitro-arginine N-t-butyl ester in the presence of dicyclohexylcarbodiimide, condensing the resulting product with glycine ethyl ester in the presence of dicyclohexylcarbodiimide, and treating the resulting product with ammonia to obtain the same compound IV as above; treating said compound IV with acid and then with N-carboxy-L-leucine N-benzyl ester 2,4,5-trichlorophenyl ester and hydrogenolyzing the resulting product in acetic acid, to obtain N-[N-[N-(N-L-leucyl)-L-arginyl]-L-prolyl]-glycinamide diacetate (V); condensing compound II with compound III by means of the azide method to obtain the hexapeptide N-[N-[N-[N-[N-(5-oxo-L-prolyl)-L-histidyl]-L-tryptophyl]-L-seryl]-L-tyrosyl]glycine 2-carboxyhydrazide t-butyl ester, or condensing N-[N-(5-oxo-L-prolyl)-L-histidyl]-L-tryptophan with compound III in the presence of dicyclohexylcarbodiimide to obtain the same hexapeptide as above, and deprotecting and converting the latter to its trifluoroacetate salt (VI); and condensing compound V with compound VI by means of the azide method, to obtain the decapeptide of formula I which is isolated as the diacetate salt and optionally converted to other pharmaceutically acceptable salts.

公开(公告)号：US4081530A

公开(公告)日：1978-03-28

申请号：US583947

申请日：1975-06-04

申请人： Hans U. Immer ,  Verner R. Nelson ,  Kazimir Sestanj

发明人： Hans U. Immer ,  Verner R. Nelson ,  Kazimir Sestanj

IPC分类号： A61K38/00 ,  C07K5/103 ,  C07K14/655 ,  A61K37/00 ,  C07C103/52

CPC分类号： C07K14/655 ,  C07K5/1008 ,  A61K38/00 ,  Y10S514/806 ,  Y10S930/16

摘要： Compounds of the formula 1 or 1a ##STR1## wherein R.sup.1 is H--, H--Gly or H--Leu and R.sup.2 is H or COOH and pharmaceutically acceptable salts thereof, are disclosed. The compounds of formulae 1 and 1a are useful for the management of diabetes and the treatment of acromegaly. Methods for their use are also disclosed.

摘要翻译： 式1或1a的化合物R1-Gly-Gly-Ala-Gly-（I）+ TRI-Gly-Gly-Ala-Gly-（Ia）+ tr其中R1是H，H -Gly或H-Leu，R2是H或COOH及其药学上可接受的盐。 式1和1a的化合物可用于治疗糖尿病和肢端肥大症的治疗。 还公开了它们的使用方法。

公开(公告)号：US4252795A

公开(公告)日：1981-02-24

申请号：US941532

申请日：1978-09-11

申请人： Amedeo Failli ,  Hans U. Immer ,  Manfred K. Gotz

发明人： Amedeo Failli ,  Hans U. Immer ,  Manfred K. Gotz

IPC分类号： C07K5/12 ,  C07K7/64 ,  A61K37/00 ,  C07C103/52

CPC分类号： C07K7/64 ,  C07K5/12 ,  Y10S930/19 ,  Y10S930/27

摘要： The N-substituted dimeric cyclopeptide derivatives of formula ##STR1## in which A is a peptide residue having one to four amino acid residues; R.sup.1 is lower alkyl, phenyl or pheny(lower) alkylene; R.sup.2 is lower alkyl, cyclo(lower)alkyl or lower alkoxycarbonyl(lower)alkylene; R.sup.3 is a neutral amino acid side chain and a method for the preparation of the compounds of formula I are disclosed. The compounds of formula I are useful for treating microbial infections. Pharmaceutical compositions also are disclosed.

摘要翻译： 式（I）的N-取代二聚环肽衍生物，其中A是具有1-4个氨基酸残基的肽残基; R1是低级烷基，苯基或苯基（低级）亚烷基; R2是低级烷基，环（低级）烷基或低级烷氧基羰基（低级）亚烷基; R3是中性氨基酸侧链，并且公开了制备式I化合物的方法。 式I化合物可用于治疗微生物感染。 也公开了药物组合物。

公开(公告)号：US4118380A

公开(公告)日：1978-10-03

申请号：US818500

申请日：1977-07-25

申请人： Hans U. Immer ,  Nedumparambil A. Abraham

发明人： Hans U. Immer ,  Nedumparambil A. Abraham

IPC分类号： A61K38/00 ,  C07K5/083 ,  C07K5/103 ,  C07K14/655 ,  C07C103/52

CPC分类号： C07K5/1005 ,  C07K14/655 ,  C07K5/0806 ,  A61K38/00 ,  Y10S930/16

摘要： Compounds of the formula 1 or 1a ##STR1##HSCH.sub.2 CH.sub.2 CO-A-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-NHCH.sub.2 CH.sub.2 SH (1a)in which A is Gly-Asn or Lys-Gly, or therapeutically acceptable salts thereof are disclosed. The compounds of formulae 1 and 1a are useful for the management of diabetes and the treatment of acromegaly in mammals. Compositions and methods for their use also are disclosed.

摘要翻译： 式1或1a的化合物（1）HSCH2CH2CO-A-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-NHCH2CH2SH（1a）其中A是Gly-Asn或Lys-Gly，或 公开了其治疗上可接受的盐。 式1和1a的化合物可用于治疗糖尿病和哺乳动物肢端肥大症的治疗。 其使用的组合物和方法也被公开。

公开(公告)号：US4018912A

公开(公告)日：1977-04-19

申请号：US599450

申请日：1975-07-28

申请人： Amedeo Failli ,  Hans U. Immer ,  Manfred Gotz

发明人： Amedeo Failli ,  Hans U. Immer ,  Manfred Gotz

IPC分类号： C07K5/08 ,  A61K38/00 ,  A61K38/06 ,  A61P25/00 ,  C07K1/02 ,  C07K1/113 ,  C07K5/097 ,  A61K37/00 ,  C07C103/52

CPC分类号： C07K5/0823 ,  Y02P20/55

摘要： The tripeptide derivatives of formula 1H--L--Pro--N(R.sup.1)CH(R.sup.2)CO--Y--R.sup.3 (1)in which R.sup.1 is hydrogen, lower alkyl or NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 each are lower alkyl, R.sup.2 is hydrogen or lower alkyl, R.sup.3 is amino, lower alkylamino, di(lower)alkylamino or amino(lower)alkylamino and Y is one of the amino acid residues Gly or D-Ala with the proviso that when R.sup.1 is NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 are as defined herein and R.sup.2 and Y are as defined herein, R.sup.3 is lower alkylamino, di(lower)alkylamino or amino(lower)alkylamino, and a method for their preparation are disclosed. The tripeptide derivatives of formula 1 possess central nervous system activity and methods for their use are given.

摘要翻译： 式1的HL-Pro-N（R1）CH（R2）CO-Y-R3（1）的三肽衍生物，其中R 1是氢，低级烷基或NR 4 R 5，其中R 4和R 5各自是低级烷基，R 2是氢或更低 烷基，R3是氨基，低级烷基氨基，二（低级）烷基氨基或氨基（低级）烷基氨基，Y是氨基酸残基Gly或D-Ala之一，条件是当R 1是NR 4 R 5时，其中R 4和R 5如本文所定义 并且R 2和Y如本文所定义，R 3是低级烷基氨基，二（低级）烷基氨基或氨基（低级）烷基氨基，并且公开了其制备方法。 式1的三肽衍生物具有中枢神经系统活性，并给出了其使用方法。

公开(公告)号：US4824937A

公开(公告)日：1989-04-25

申请号：US50208

申请日：1987-05-14

申请人： Romano Deghenghi ,  Hans U. Immer

发明人： Romano Deghenghi ,  Hans U. Immer

IPC分类号： C07K14/575 ,  A61K38/00 ,  A61P9/08 ,  A61P9/12 ,  C07K14/00 ,  C07K14/58 ,  C07K7/10

CPC分类号： C07K14/582 ,  A61K38/00

摘要： Synthetic natriuretic peptides (SNP) composed of 23 amino acid residues of which residues 2-23 have the natural L-configuration while the amino-terminal residue is derived from an unnatural amino acid having the D-configuration. The compounds possess diuretic, natriuretic, vasorelaxant, smooth muscle relaxant, hypotensive, and anti-hypertensive activities, and a process for their preparation is also disclosed, together with pharmaceutical preparations thereof and with their use in the practice of medicine. Salts of said synthetic natriuretic peptides with pharmaceutically acceptable acids are also disclosed.

摘要翻译： 由23个氨基酸残基组成的合成利钠肽（SNP），其中残基2-23具有天然的L-构型，而氨基末端残基源自具有D-构型的非天然氨基酸。 该化合物具有利尿，利尿钠，血管舒张，平滑肌松弛剂，降血压和抗高血压活性，并且还公开了其制备方法及其药物制剂及其在药物实践中的用途。 还公开了所述合成利钠肽与药学上可接受的酸的盐。

公开(公告)号：USRE30496E

公开(公告)日：1981-01-27

申请号：US15091

申请日：1979-02-26

申请人： Amedeo Failli ,  Hans U. Immer ,  Manfred K. Gotz

发明人： Amedeo Failli ,  Hans U. Immer ,  Manfred K. Gotz

IPC分类号： C07K5/097

CPC分类号： C07K5/0823

摘要： The tripeptide derivatives of formulaH--L--Pro--N(R.sup.1)CH(R.sup.2)CO--Y--R.sup.3 (1)in which R.sup.1 is hydrogen, lower alkyl or NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 each are lower alkyl, R.sup.2 is hydrogen or lower alkyl, R.sup.3 is amino, lower alkylamino, di(lower)alkylamino or amino(lower)alkylamino and Y is one of the amino acid residues Gly or D-Ala with the proviso that when R' is NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 are as defined herein and R.sup.2 and Y are as defined herein, R.sup.3 is lower alkylamino, di(lower)alkylamino or amino(lower)alkylamino, .Iadd.and with the further proviso that when R.sup.1 is hydrogen, R.sup.2 is hydrogen or lower alkyl and Y is Gly then R.sup.3 is amino(lower)alkylamino, .Iaddend.and a method for their preparation are disclosed. The tripeptide derivatives of formula 1 possess central nervous system activity and methods for their use are given.