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公开(公告)号：US5032507A
公开(公告)日：1991-07-16
申请号：US120470
申请日：1987-11-13
申请人： John Yu , Alice L. Yu , Joan Vaughan , Jean E. F. Rivier , Wylie W. Vale, Jr.
发明人： John Yu , Alice L. Yu , Joan Vaughan , Jean E. F. Rivier , Wylie W. Vale, Jr.
IPC分类号： A61K38/00 , A61K38/04 , A61K38/22 , A61P7/00 , C07K14/435 , C07K14/575
CPC分类号： A61K38/22 , Y10S435/81
摘要： A method for modulating the rate of erythropoiesis in human hematopoietic progenitor cells. FRP is found to be an efficacious potentiator of, and inhibin a suppressor of, erythropoietin-induced differentiation. FRP and inhibin are shown to be functional antagonists of each other, and thus represent an effective means for modulating erythropoiesis in a number of disease states which are directly caused by or associated with an abnormal rate of erythropoiesis.
摘要翻译： 调节人类造血祖细胞中红细胞生成速率的方法。 发现FRP是促红细胞生成素诱导分化的有效增效剂，抑制抑制素。 FRP和抑制素显示为彼此的功能性拮抗剂，因此代表了直接由异常红细胞生成速率引起或与之相关的许多疾病状态调节红细胞生成的有效手段。
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公开(公告)号：US4628043A
公开(公告)日：1986-12-09
申请号：US714687
申请日：1985-03-21
CPC分类号： C07K14/60 , A23K20/147 , A61K38/00 , Y10S930/12
摘要： Synthetic peptides are provided which are extremely potent in stimulating the release of pituitary GH in animals and which have the formula: H--R.sub.1 --Ala--Asp--Ala--Ile--Phe--Thr--R.sub.8 --Ser--R.sub.10 --Arg--R.sub.12 --R.sub.13 --Leu--R.sub.15 --Gln--Leu--R.sub.18 --Ala--Arg--Lys--Leu--Leu--R.sub.24 --R.sub.25 --Ile--R.sub.27 --R.sub.28 --Arg--Gln--Gln--Gly--Glu--R.sub.34 --Asn--Gln--Glu--R.sub.38 --R.sub.39 --R.sub.40 --Arg--R.sub.42 --R.sub.43 --Leu--Y wherein R.sub.1 is Tyr, Met, Leu, D--Tyr, D--His or His; R.sub.8 is Ser or Asn; R.sub.10 is Tyr or D--Tyr; R.sub.12 is Arg or Lys; R.sub.13 is Ile or Val; R.sub.15 is Gly or D--Ala; R.sub.18 is Tyr or Ser; R.sub.24 is His or Gln; R.sub.25 is Glu or Asp; R.sub.27 is Met, Ala, Nle, Ile, Leu or Val; R.sub.28 is Asn or Ser; R.sub.34 is Arg or Ser; R.sub.38 is Gln or Arg; R.sub.39 is Arg or Gly; R.sub.40 is Ser or Ala; R.sub.42 is Phe or Ala; R.sub.43 is Asn or Arg; and Y represents the carboxyl moiety of the amino acid residue at the C-terminus and is the radical --COOR,--CRO,--CONHNHR, --CON(R)(R') or --CH.sub.2 OR, with R and R' being lower alkyl, fluoro lower alkyl or hydrogen, or a fragment thereof extending from the N-terminus in a continuous sequence at least to the residue in position 29, which fragment is biologically active to cause the release of GH from the pituitary, or a nontoxic salt of such peptide or peptide fragment. The peptides are analogs of human GRF and contain at least two but less than all of the following residues: R.sub.8 is Asn, R.sub.12 is Lys, R.sub.13 is Val, R.sub.18 is Ser, R.sub.24 is Gln, R.sub.25 is Asp, R.sub.28 is Ser.
摘要翻译： 提供了合成肽，其在刺激动物中垂体GH的释放方面非常有效，其具有下式：H-R1-Ala-Asp-Ala-Ile-Phe-Thr-R8-Ser-R10-Arg-R12-R13 -Leu-R15-Gln-Leu-R1 8-Ala-Arg-Lys-Leu-Leu-R24-R25-Ile-R27-R28-Arg-Gln-Gln-Gly-Glu-R34-Asn-Gln-Glu- R38-R39-R40-Arg-R42-R43-Leu-Y，其中R1是Tyr，Met，Leu，D-Tyr，D-His或His; R8是Ser或Asn; R10是Tyr或D-Tyr; R12是Arg或Lys; R13是Ile或Val; R15是Gly或D-Ala; R18是Tyr或Ser; R24是His或Gln; R25是Glu或Asp; R27是Met，Ala，Nle，Ile，Leu或Val; R28为Asn或Ser; R34是Arg或Ser; R38是Gln或Arg; R39是Arg或Gly; R40是Ser或Ala; R42是Phe或Ala; R43是Asn或Arg; 并且Y代表C末端的氨基酸残基的羧基部分，并且是基团-COOR，-CRO，-CONHNHR，-CON（R）（R'）或-CH 2 OR，其中R和R'是低级烷基 ，氟低级烷基或氢，或其从N末端以连续序列至少延伸至位置29的残基的片段，该片段具有生物学活性以引起GH从垂体中释放，或无毒盐 这样的肽或肽片段。 肽是人GRF的类似物，并且含有至少两个但少于所有以下残基：R8是Asn，R12是Lys，R13是Val，R18是Ser，R24是Gln，R25是Asp，R28是Ser。
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公开(公告)号：US4595676A
公开(公告)日：1986-06-17
申请号：US488748
申请日：1983-04-26
CPC分类号： C07K14/60 , A23K20/147 , A61K38/00 , Y10S930/12
摘要： Rat hypothalamic GRF has been synthesized and has the formula: H-His-Ala-Asp-Ala-Ile-Phe-Thr-Ser-Ser-Tyr-Arg-Arg-Ile-Leu-Gly-Gln-Leu-Tyr-Ala-Arg-Lys-Leu-Leu-His-Glu-Ile-Met-Asn-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu-Gln-Arg-Ser-Arg-Phe-Asn-OH. The peptide is believed to be and is hereinafter referred to as rhGRF (for rat hypothalamic GH releasing factor). The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in animals and which have the formula: H-R.sub.1 -Ala-Asp-Ala-Ile-Phe-Thr-R.sub.8 -Ser-R.sub.10 -Arg-R.sub.12 -R.sub.13 -Leu-R.sub.15 -Gln-Leu-R.sub.18 -Ala-Arg-Lys-Leu-Leu-R.sub.24 -R.sub.25 -Ile-R.sub.27 -R.sub.28 -Arg-Gln-Gln-Gly-Glu-R.sub.34 -Asn-Gln-Glu-R.sub.38 -R.sub.39 -R.sub.40 -Arg-R.sub.42 -R.sub.43 -R.sub.44 -Y wherein R.sub.1 is Tyr, Met, D-Tyr, Leu, D-His or His; R.sub.8 is Ser or Asn; R.sub.10 is Tyr or D-Tyr; R.sub.12 is Arg or Lys; R.sub.13 is Ile or Val; R.sub.15 is Gly or D-Ala; R.sub.18 is Tyr or Ser; R.sub.24 is His or Gln; R.sub.25 is Glu or Asp; R.sub.27 is Met, Ala, Nle, Ile, Leu or Val; R.sub.28 is Asn or Ser; R.sub.34 is Arg or Ser; R.sub.38 is Gln or Arg; R.sub.39 is Arg or Gly; R.sub.40 is Ser or Ala; R.sub.42 is Phe or Ala; R.sub.43 is Asn or Arg; R.sub.44 is a natural amino acid or des-R.sub.44 ; and Y signifies the carboxyl moiety of the amino acid residue at the C-terminus and is the radical --COOR,--CRO,--CONHNHR,--CON(R)(R') or --CH.sub.2 OR, with R and R' being lower alkyl, fluoro lower alkyl or hydrogen.These peptides or biologically active fragments thereof, or analogs thereof having well-known substitutions and/or additions, as well as nontoxic salts of any of the foregoing, may be administered to animals, including humans, to stimulate the release of GH and may be used diagnostically.
摘要翻译： 已经合成了大鼠下丘脑GRF，具有下式：H-His-Ala-Asp-Ala-Ile-Phe-Thr-Ser-Ser-Tyr-Arg-Arg-Ile-Leu-Gly-Gln-Leu-Ala -Arg-Lys-Leu-Leu-His-Glu-Ile-Met-Asn-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu-Gln-Arg-Ser-Arg-Phe- 哦。 该肽被认为是并且在下文中被称为rhGRF（对于大鼠下丘脑GH释放因子）。 本发明提供了在动物中刺激垂体GH的释放非常有效的合成肽，其具有下式：H-R1-Ala-Asp-Ala-Ile-Phe-Thr-R8-Ser-R10-Arg-R12- R13-Leu-R15-Gln-Leu-R1 8-Ala-Arg-Lys-Leu-Leu-R24-R25-Ile-R27-R28-Arg-Gln-Gln-Gly-Glu-R34-Asn-Gln-Glu -R38-R39-R40-Arg-R42-R43-R44-Y，其中R1是Tyr，Met，D-Tyr，Leu，D-His或His; R8是Ser或Asn; R10是Tyr或D-Tyr; R12是Arg或Lys; R13是Ile或Val; R15是Gly或D-Ala; R18是Tyr或Ser; R24是His或Gln; R25是Glu或Asp; R27是Met，Ala，Nle，Ile，Leu或Val; R28为Asn或Ser; R34是Arg或Ser; R38是Gln或Arg; R39是Arg或Gly; R40是Ser或Ala; R42是Phe或Ala; R43是Asn或Arg; R44是天然氨基酸或des-R44; 并且Y表示C末端的氨基酸残基的羧基部分，并且是基团-COOR，-CRO，-CONHNHR，-CON（R）（R'）或-CH 2OR，其中R和R'为低级烷基 氟代低级烷基或氢。 这些具有众所周知的取代和/或添加的肽或其类似物或其类似物以及前述任何一种的无毒盐可以被给予动物，包括人，以刺激GH的释放，并且可以是 用于诊断。
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公开(公告)号：US4563352A
公开(公告)日：1986-01-07
申请号：US432663
申请日：1982-10-04
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 , A61K37/02
CPC分类号： C07K14/60 , A61K38/00 , Y10S530/845 , Y10S930/12
摘要： Human pancreatic GRF has been synthesized. The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in mammals and which have the formula: H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-R.sub.15 -Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-R.sub.40 -R.sub.41 -R.sub.42 -Y wherein R.sub.15 is Gly or D-Ala, R.sub.40 is Ala or des-R.sub.40, R.sub.41 is Phe or des-R.sub.41, R.sub.42 is des-R.sub.42 or 1 to 8 different amino acid residues selected from the group consisting of Gln, Gly, Ile, Leu, Lys, Pro, Thr and Val, and Y signifies the carboxyl moiety of the amino acid residue at the C-terminal and is the radical -COOR.sub.1,-CR.sub.1 O,-CONHNHR.sub.1,-CON(R.sub.1)(R.sub.2) or -CH.sub.2 OR.sub.1, with R.sub.1 and R.sub.2 being lower alkyl or hydrogen. These peptides or biologically active fragments thereof, or analogs thereof having well-known substitutions and/or additions, as well as nontoxic salts of any of the foregoing, may be administered therapeutically to animals, including humans, and may be used diagnostically.
摘要翻译： 人胰腺GRF已被合成。 本发明提供了非常有效刺激哺乳动物垂体GH释放的合成肽，其具有下式：H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys- Val-Leu-R15-Gln-Leu- Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu -Arg-Gly-R40-R41-R42-Y，其中R15是Gly或D-Ala，R40是Ala或des-R40，R41是Phe或des-R41，R42是des-R42或1到8个不同的氨基酸残基 选自Gln，Gly，Ile，Leu，Lys，Pro，Thr和Val组成的组，Y表示C-末端的氨基酸残基的羧基部分，是-COOR1，-CR1O，-CONHNHR1基团 ，-CON（R 1）（R 2）或-CH 2 OR 1，其中R 1和R 2为低级烷基或氢。 具有众所周知的取代和/或添加的这些肽或其类似物或其类似物以及前述任何一种的无毒盐可以治疗性地给予动物，包括人，并且可以在诊断上使用。
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公开(公告)号：US4489163A
公开(公告)日：1984-12-18
申请号：US484931
申请日：1983-04-14
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 , G01N1/00 , A61K37/00 , C07C103/52
CPC分类号： C07K14/57509 , A61K38/00
摘要： rCRF (rat Corticotropin Releasing Factor) has been isolated, characterized and found to 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-NH.sub.2. Analogs are disclosed that are at least as potent as rCRF, and rCRF or these analogs orpharmaceutically or veterinarily acceptable salts thereof, dispersed in a pharmaceutically or veterinarily acceptable liquid or solid carrier, can be administered to animals, 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.
摘要翻译： 已经分离了rCRF（大鼠促肾上腺皮质激素释放因子），其特征为：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-Ar g-Lys-Leu-Met- Ile-Ile-NH2。 公开了至少与rCRF一样有效的类似物，并且可将rCRF或其分散在药学上或兽医学上可接受的液体或固体载体中的这些类似物或其药学上或兽医学上可接受的盐施用于包括人在内的动物以达到显着升高 的ACTH，β-内啡肽，β-促性腺激素，其他产物的前乳糖皮质素基因和皮质酮水平和/或在较长时间内降低血压。 它们也可以用作兴奋剂来提升心情，改善记忆和学习以及诊断。 在类似物中，前三个N末端残基中的一个或多个可以被缺失或可被长达10个氨基酸的肽和/或被含有至多7个碳原子的酰化剂所取代。 还可以在整个链中进行许多其它取代。
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公开(公告)号：US5493006A
公开(公告)日：1996-02-20
申请号：US078558
申请日：1993-06-16
IPC分类号： A61K38/00 , C07K14/575 , C07K14/695
CPC分类号： C07K14/57509 , A61K38/00
摘要： Improved CRF peptide antagonists have the formula: ##STR1## wherein R.sub.20 is Cys or Glu; R.sub.23 is Cys, Lys or Orn; provided that when R.sub.20 is Cys, R.sub.23 is Cys and when R.sub.20 is Glu, R.sub.23 is Lys or Orn; or a nontoxic addition salt thereof. Specific CRF antagonists disclosed include (cyclo 20-23) [D-Phe.sup.12, Lys.sup.23, Nle.sup.21,38, ]rCRF(12-41); (cyclo 20-23) [D-Phe.sup.12, Orn.sup.23, Nle.sup.21,38 ]rCRF(12-41) and (cyclo 20-23) [D-Phe.sup.12, Cys.sup.20, Cys.sup.23, Nle.sup.21,38 ]rCRF(12-41).
摘要翻译： 改进的CRF肽拮抗剂具有下式：其中R 20是Cys或Glu; R23是Cys，Lys或Orn; 条件是当R 20为Cys时，R 23为Cys，当R 20为Glu时，R 23为Lys或Orn; 或其无毒的加成盐。 公开的具体CRF拮抗剂包括（环20-23）[D-Phe12，Lys23，Nle21,38] rCRF（12-41）; （环20-23）[D-Phe12，Orn23，Nle21,38] rCRF（12-41）和（环20-23）[D-Phe12，Cys20，Cys23，Nle21,38] rCRF（12-41）。
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公开(公告)号：US5296468A
公开(公告)日：1994-03-22
申请号：US6729
申请日：1993-01-21
申请人： Carl A. Hoeger , Jean E. F. Rivier , Paula G. Theobald , John S. Porter , Catherine L. Rivier , Wylie W. Vale, Jr.
发明人： Carl A. Hoeger , Jean E. F. Rivier , Paula G. Theobald , John S. Porter , Catherine L. Rivier , Wylie W. Vale, Jr.
IPC分类号： A61K38/00 , C07C279/24 , C07C279/28 , C07C313/30 , C07D249/14 , C07K7/02 , C07K7/23 , A61K37/38 , C07K7/06 , C07K7/20
CPC分类号： C07K7/02 , C07C279/24 , C07C279/28 , C07C313/30 , C07D249/14 , C07K7/23 , A61K38/00 , C07C2101/14 , Y10S514/80 , Y10S930/11
摘要： Peptides which include unnatural amino acids and which either inhibit or promote the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount of such peptides that are GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. The antagonists may be used to treat steroid-dependent tumors, such as prostatic and mammary tumors. The peptides are analogs of the decapeptide GnRH wherein there is at least one residue of an unnatural amino acid in the 3-, 5-, 6- and/or 8-positions. Such unnatural amino acids are useful in the synthesis of peptides and have the formula U.sup.* : ##STR1## where W is (CH.sub.2).sub.n or ##STR2## n is an integer from 1 to 6; and j=1, 2 or 3. Preferably, either Y is N--CN, X is NH and R.sub.2 is alkyl, modified alkyl, alkenyl, alkynyl, aryl or methyl pridyl or ##STR3## where R.sub.11 is H or acyl.
摘要翻译： 包括非天然氨基酸的肽，其通过垂体抑制或促进促性腺激素的分泌并抑制性腺释放类固醇。 施用有效量的这种肽作为GnRH拮抗剂可防止雌性哺乳动物卵的排卵和/或由性腺释放类固醇。 拮抗剂可用于治疗类固醇依赖性肿瘤，例如前列腺和乳腺肿瘤。 肽是十肽GnRH的类似物，其中在3-，5-，6-和/或8-位存在至少一个非天然氨基酸残基。 这样的非天然氨基酸可用于肽的合成，并具有其中W是（CH 2）n或（*化学结构*）n是1至6的整数的式U *：（*化学结构*）; 优选地，Y是N-CN，X是NH，R 2是烷基，改性烷基，链烯基，炔基，芳基或甲基酰基或（*化学结构*），其中R 11是H或酰基 。
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公开(公告)号：US5262519A
公开(公告)日：1993-11-16
申请号：US701414
申请日：1991-05-15
CPC分类号： C07K14/60
摘要： The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in animals, including humans and also resist enzymatic degradation in the body. Certain preferred peptides have the formula:(B)R.sub.1 -Ala-Asp-Ala-Ile-Phe-Thr-R.sub.8 -Ser-Tyr-Arg-Lys-Val-Leu-R.sub.15 -R.sub.16 - Leu-Ser-Ala-Arg-Lys-Leu-Leu-R.sub.24 -R.sub.25 -Ile-Nle-R.sub.28 -Arg-Y wherein R.sub.1 is Tyr, D-Tyr, Phe, D-Phe, His or D-His; B is H or N.sup..alpha. Me; R.sub.8 is Ala, Aib or Asn; R.sub.15 is Gly or Ala; R.sub.16 is Ala, Aib or Gln; R.sub.24 is Ala, Aib or Gln; R.sub.25 is Ala, Aib or Asp; R.sub.28 is Ser or Asn; Y is NHR with R being H or lower alkyl; provided that at least one of R.sub.8, R.sub.16, R.sub.24 and R.sub.25 is Ala or Aib.
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公开(公告)号：US5245009A
公开(公告)日：1993-09-14
申请号：US715752
申请日：1991-06-14
申请人： Wayne D. Kornreich , Jean-Francois Hernandez , Jean E. F. Rivier , Catherine L. Rivier , Wylie W. Vale, Jr.
发明人： Wayne D. Kornreich , Jean-Francois Hernandez , Jean E. F. Rivier , Catherine L. Rivier , Wylie W. Vale, Jr.
IPC分类号： A61K38/00 , C07K14/575
CPC分类号： C07K14/57509 , A61K38/00 , Y10S930/26
摘要： Disclosed are improved CRF peptide antagonists such as those having the formula: Y-D-Phe-R.sub.13 -Leu-Leu-Arg-R.sub.17 -R.sub.18 -Leu-R.sub.20 -Nle-R.sub.22 -R.sub.23 -R.sub.24 -R.sub.25 -R.sub.26 -Leu-R.sub.28 -R.sub.29 -Gln-R.sub.31 -R.sub.32 -R.sub.33 -R.sub.34 -Arg-R.sub.36 -R.sub.37 -Nle-R.sub.39 -R.sub.40 -R.sub.41 -NH.sub.2 wherein Y is Ac or hydrogen; R.sub.13 is His, Tyr or Glu; R.sub.17 is Cys, Glu, Asn or Lys; R.sub.18 is Val, Nle or Met; R.sub.20 is D-Cys, Glu, D-Glu, Aib or D-Ala; R.sub.22 is Ala, Aib, Thr, Asp or Glu; R.sub.23 is Arg, Orn, Har or Lys; R.sub.24 is Ala or Aib; R.sub.25 is Asp or Glu; R.sub.26 is Gln, Asn or Lys; R.sub.28 is Ala or Aib; R.sub.29 is Gln, Aib or Glu, R.sub.31 is Ala or Aib; R.sub.32 is His, Aib, Gly, Tyr or Ala; R.sub.33 is Ser, Aib, Asn, Leu, Thr or Ala; R.sub.34 is Asn or Aib; R.sub.36 is Lys, Orn, Arg, Har or Leu; R.sub.37 is Leu or Try; R.sub.39 is Glu, Aib or Asp; R.sub.40 is Ile, Aib, Thr, Glu, Ala, Val, Leu, Nle, Phe, Nva, Gly or Gln; and R.sub.41 is Ala, Ile, Gly, Val, Leu, Nle, Phe, Nva or Gln. Specific CRF antagonists disclosed include [D-Phe.sup.12, D-Ala.sup.20, Nle.sup.21,38,]-rCRF(12-41), [D-Phe.sup.12, Nle.sup.21,38, Aib.sup.33 ]-rCRF(12-41) and (c 17-20) [D-Phe.sup.12, Cys.sup.17, D-Cys.sup.20, Nle.sup.21,38 ]-rCRF(12-41).
摘要翻译： 公开了改进的CRF肽拮抗剂，例如具有下式的那些：肽，如YD-Phe-R13-Leu-Leu-Arg-R17-R18-Leu-R20-Nle-R22-R23-R24-R25-R26-Leu-R2 8- R29-Gln-R31-R32-R33-R34-Arg-R36-R37-Nle-R39-R40-R41-NH2，其中Y是Ac或氢; R13是His，Tyr或Glu; R17是Cys，Glu，Asn或Lys; R18为Val，Nle或Met; R20是D-Cys，Glu，D-Glu，Aib或D-Ala; R22是Ala，Aib，Thr，Asp或Glu; R23是Arg，Orn，Har或Lys; R24是Ala或Aib; R25为Asp或Glu; R26是Gln，Asn或Lys; R28是Ala或Aib; R29是Gln，Aib或Glu，R31是Ala或Aib; R32是His，Aib，Gly，Tyr或Ala; R33是Ser，Aib，Asn，Leu，Thr或Ala; R34是Asn或Aib; R36是Lys，Orn，Arg，Har或Leu; R37是Leu或Try; R39是Glu，Aib或Asp; R40是Ile，Aib，Thr，Glu，Ala，Val，Leu，Nle，Phe，Nva，Gly或Gln; R41是Ala，Ile，Gly，Val，Leu，Nle，Phe，Nva或Gln。 公开的具体的CRF拮抗剂包括[D-Phe12，D-Ala20，Nle21,38] -rCRF（12-41），[D-Phe12，Nle21,38，Aib33] -rCRF（12-41）和（c17- 20）[D-Phe12，Cys17，D-Cys20，Nle21,38] -rCRF（12-41）。
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公开(公告)号：US5235036A
公开(公告)日：1993-08-10
申请号：US709091
申请日：1991-05-31
IPC分类号： A61K38/00 , C07K14/575
CPC分类号： C07K14/57509 , A61K38/00 , Y10S930/26
摘要： Analogs of CRF, which are based upon hCRF, oCRF and alpha-helical CRF, are disclosed that can be administered to achieve a substantial elevation of ACTH, .beta.-endorphin, .beta.-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone levels. Analogs include those having the formula: Y-R.sub.1 -R.sub.2 -R.sub.3 -R.sub.4 -R.sub.5 -Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-R.sub.20 -R.sub.21 -R.sub.22 -R.sub.23 -R.sub.24 -R.sub.25 -Gln-Leu-Ala-Gln-Gln-Ala-R.sub.32 -Ser-Asn-Arg-Lys-Leu-R.sub.38 -R.sub.39 -Ile-R.sub.41 -NH.sub.2, wherein Y is an acyl group having 7 or fewer carbon atoms or hydrogen; R.sub.1 is Ser or desR.sub.1 ; R.sub.2 is Glu, Gln or desR.sub.2 ; R.sub.3 is Glu or desR.sub.3 ; R.sub.4 is Pro or desR.sub.4 ; R.sub.5 is Pro or desR.sub.5 ; R.sub.20 is Ala or Glu; R.sub.21 is Met or Nle; R.sub.22 is Ala or Thr; R.sub.23 is Arg or Lys; R.sub.24 is D-Ala or Ala; R.sub.25 is Glu or Asp; R.sub.32 is D-His or His; R.sub.38 is Met, Nle or Leu; R.sub.39 is Ala, Glu or Asp; R.sub.41 is Ile or Ala; provided however that at least one of R.sub.20 and R.sub.39 is Ala. One example is [Ala.sup.20 ]-oCRF. These analogs or their pharmaceutically acceptable salts, dispersed in an acceptable liquid or solid carrier, can be administered to humans.
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