公开(公告)号：US07026281B1

公开(公告)日：2006-04-11

申请号：US09547215

申请日：2000-04-11

申请人： Andrew V. Schally ,  Jozsef Varga ,  Marta Zarandi

发明人： Andrew V. Schally ,  Jozsef Varga ,  Marta Zarandi

IPC分类号： A61K38/00

CPC分类号： C07K14/60 ,  A61K38/00

摘要： There is provided a novel series of synthetic analogs of hGH-RH(1–29)NH2. These analogs inhibit the activity of endogenous hGH-RH, and therefore prevent the release of growth hormone. The stronger inhibitory potencies of the new analogs, as compared to previously described ones, results from replacement of various amino acids.

摘要翻译： 提供了一系列hGH-RH（1-29）NH 2的合成类似物。 这些类似物抑制内源性hGH-RH的活性，从而阻止生长激素的释放。 与之前描述的相比，新类似物的更强的抑制效力来自各种氨基酸的置换。

公开(公告)号：US08691942B2

公开(公告)日：2014-04-08

申请号：US12890626

申请日：2010-09-25

申请人： Andrew V. Schally ,  Marta Zarandi ,  Jozsef L. Varga ,  Ren Zhi Cai

发明人： Andrew V. Schally ,  Marta Zarandi ,  Jozsef L. Varga ,  Ren Zhi Cai

IPC分类号： C07K14/60 ,  A61K38/25

CPC分类号： A61K38/25 ,  A61K38/00 ,  C07K14/60 ,  C07K14/645

摘要： There is provided a novel series of synthetic analogs of hGH-RH(1-29)NH2 (SEQ ID NO: 1) and hGH-RH(1-30)NH2. Of particular interest are those carrying PhAc, N-Me-Aib, Dca, Ac-Ada, Fer, Ac-Amc, Me-NH-Sub, PhAc-Ada, Ac-Ada-D-Phe, Ac-Ada-Phe, Dca-Ada, Dca-Amc, Nac-Ada, Ada-Ada, or CH3—(CH2)10—CO-Ada, at the N-Terminus and β-Ala, Amc, Apa, Ada, AE2A, AE4P, ε-Lys(α-NH2), Agm, Lys(Oct) or Ahx, at the C-terminus. These analogs inhibit the release of growth hormone from the pituitary in mammals as well as inhibit the proliferation of human cancers, and inhibit the hyperplastic and benign proliferative disorders of various organs, through a direct effect on the cancerous and non-malignant cells. The stronger inhibitory potencies of the new analogs, as compared to previously described ones, result from replacement of various amino acids.

摘要翻译： 提供了一系列hGH-RH（1-29）NH2（SEQ ID NO：1）和hGH-RH（1-30）NH2的合成类似物。 特别感兴趣的是携带PhAc，N-Me-Aib，Dca，Ac-Ada，Fer，Ac-Amc，Me-NH-Sub，PhAc-Ada，Ac-Ada-D-Phe，Ac-Ada-Phe， Dca-Ada，Dca-Amc，Nac-Ada，Ada-Ada或CH 3 - （CH 2）10-CO-Ada，在N-Terminus和-Ab，-Ala，Amc，Apa，Ada，AE2A，AE4P， ; -Lys（α-NH2），Agm，Lys（Oct）或Ahx。 这些类似物通过对癌和非恶性细胞的直接作用，抑制哺乳动物垂体中生长激素的释放以及抑制人类癌症的增殖，并抑制各种器官的增生和良性增生性疾病。 与之前描述的相比，新类似物的更强的抑制效力是由于各种氨基酸的替换而产生的。

公开(公告)号：US20100092539A1

公开(公告)日：2010-04-15

申请号：US12562096

申请日：2009-09-17

申请人： Andrew Schally ,  Jozsef Varga ,  Marta Zarandi ,  Ren Zhi Cai ,  Norman L. Block

发明人： Andrew Schally ,  Jozsef Varga ,  Marta Zarandi ,  Ren Zhi Cai ,  Norman L. Block

IPC分类号： A61F2/00 ,  C07K14/00 ,  A61K38/16 ,  A61P35/04

CPC分类号： C07K14/60 ,  A61K38/00

摘要： Novel fluorinated synthetic analogs of hGH-RH(1-30)NH2 that inhibit the release of growth hormone from the pituitary in mammals as well as inhibit the proliferation of human cancers through a direct effect on the cancer cells, and to therapeutic compositions containing these novel peptides and their use.

摘要翻译： hGH-RH（1-30）NH2的新型氟化合成类似物，其抑制哺乳动物垂体中生长激素的释放，并且通过对癌细胞的直接作用抑制人类癌症的增殖，以及含有这些的治疗组合物 新型肽及其用途。

公开(公告)号：US20070042950A1

公开(公告)日：2007-02-22

申请号：US10566776

申请日：2004-07-26

申请人： Andrew Schally ,  Jozsef Varga ,  Marta Zarandi ,  Ren Cai

发明人： Andrew Schally ,  Jozsef Varga ,  Marta Zarandi ,  Ren Cai

IPC分类号： A61K38/16 ,  C07K14/47

CPC分类号： C07K14/60 ,  A61K38/00

摘要： There is provided a novel series of synthetic antagonistic analogs of hGH-RH(1-29)NH2. These analogs inhibit the activity of endogenous hGH-RH on the pituitary GH-RH receptors, and therefore prevent the release of growth hormone. The analogs also inhibit the proliferation of human cancers through a direct effect on the cancer cells. The higher inhibitory potencies of the new analogs, as compared to previously described ones, results from replacement of various amino acids.

摘要翻译： 提供了一系列hGH-RH（1-29）NH 2的合成拮抗类似物。 这些类似物抑制内源性hGH-RH对垂体GH-RH受体的活性，因此防止生长激素的释放。 类似物还通过对癌细胞的直接作用来抑制人类癌症的增殖。 与之前描述的相比，新类似物的更高的抑制效力来自各种氨基酸的替换。

公开(公告)号：US20140058068A1

公开(公告)日：2014-02-27

申请号：US13332624

申请日：2011-12-21

申请人： Andrew V. Schally ,  Ren Zhi Cai ,  Marta Zarandi

发明人： Andrew V. Schally ,  Ren Zhi Cai ,  Marta Zarandi

IPC分类号： C07K14/61

CPC分类号： C07K14/60 ,  A61K38/00 ,  C07K14/61

摘要： There are provided a novel series of peptide analogs of hGH-RH(1-29)NH2 and hGH-RH(1-30)NH2 which show high activities in stimulating the release of pituitary GH in animals. They retain their physiological activity in solution for extended periods of time and resist enzymic degradation in the body. These novel and useful properties appear to be due to novel substitution patterns ant at the 1, 15, 27 and 29 positions on the peptide.

摘要翻译： 提供了一系列hGH-RH（1-29）NH2和hGH-RH（1-30）NH2的肽类似物，其在刺激动物中垂体GH的释放方面表现出高的活性。 它们在溶液中保持长时间的生理活性，并抵抗体内酶降解。 这些新颖有用的性质似乎是由于肽上的1,15,27和29位的新型取代模式蚂蚁。

公开(公告)号：US20110066230A1

公开(公告)日：2011-03-17

申请号：US12562010

申请日：2009-09-17

申请人： Andrew Schally ,  Jozsef Varga ,  Marta Zarandi ,  Ren Zhi Cai ,  Norman L. Block

发明人： Andrew Schally ,  Jozsef Varga ,  Marta Zarandi ,  Ren Zhi Cai ,  Norman L. Block

IPC分类号： A61F2/82 ,  C07K14/00 ,  A61K38/16 ,  A61P9/10 ,  A61P35/00

CPC分类号： A61K9/0019 ,  A61K38/00 ,  C07K14/60

摘要： Novel fluorinated synthetic analogs of hGH-RH(1-30)NH2 that inhibit the release of growth hormone from the pituitary in mammals as well as inhibit the proliferation of human cancers through a direct effect on the cancer cells, and to therapeutic compositions containing these novel peptides and their use.

摘要翻译： hGH-RH（1-30）NH2的新型氟化合成类似物，其抑制哺乳动物垂体中生长激素的释放，并且通过对癌细胞的直接作用抑制人类癌症的增殖，以及含有这些的治疗组合物 新型肽及其用途。

公开(公告)号：US07452865B2

公开(公告)日：2008-11-18

申请号：US10566776

申请日：2004-07-26

申请人： Andrew V. Schally ,  Jozsef Varga ,  Marta Zarandi ,  Ren Zhi Cai

发明人： Andrew V. Schally ,  Jozsef Varga ,  Marta Zarandi ,  Ren Zhi Cai

IPC分类号： A61K38/00 ,  A61K38/16 ,  A61K38/25 ,  C07K14/00

CPC分类号： C07K14/60 ,  A61K38/00

摘要： There is provided a novel series of synthetic antagonistic analogs of hGH-RH(1-29)NH2. These analogs inhibit the activity of endogenous hGH-RH on the pituitary GH-RH receptors, and therefore prevent the release of growth hormone. The analogs also inhibit the proliferation of human cancers through a direct effect on the cancer cells. The higher inhibitory potencies of the new analogs, as compared to previously described ones, results from replacement of various amino acids.

摘要翻译： 提供了一系列hGH-RH（1-29）NH 2的合成拮抗类似物。 这些类似物抑制内源性hGH-RH对垂体GH-RH受体的活性，因此防止生长激素的释放。 类似物还通过对癌细胞的直接作用来抑制人类癌症的增殖。 与之前描述的相比，新类似物的更高的抑制效力来自各种氨基酸的替换。

公开(公告)号：US09079974B2

公开(公告)日：2015-07-14

申请号：US13332624

申请日：2011-12-21

申请人： Andrew V Schally ,  Ren Zhi Cai ,  Marta Zarandi

发明人： Andrew V Schally ,  Ren Zhi Cai ,  Marta Zarandi

IPC分类号： A61K38/00 ,  C07K2/00 ,  C07K4/00 ,  C07K5/00 ,  C07K7/00 ,  C07K14/00 ,  C07K16/00 ,  C07K17/00 ,  A61K38/24 ,  A61K38/27 ,  C07K1/00 ,  C07K14/61 ,  C07K14/60

CPC分类号： C07K14/60 ,  A61K38/00 ,  C07K14/61

摘要： There are provided a novel series of peptide analogs of hGH-RH(1-29)NH2 and hGH-RH(1-30)NH2 which show high activities in stimulating the release of pituitary GH in animals. They retain their physiological activity in solution for extended periods of time and resist enzymic degradation in the body. These novel and useful properties appear to be due to novel substitution patterns ant at the 1, 15, 27 and 29 positions on the peptide.

摘要翻译： 提供了一系列hGH-RH（1-29）NH2和hGH-RH（1-30）NH2的肽类似物，其在刺激动物中垂体GH的释放方面表现出高的活性。 它们在溶液中保持长时间的生理活性，并抵抗体内酶降解。 这些新颖有用的性质似乎是由于肽上的1,15,27和29位的新型取代模式蚂蚁。

公开(公告)号：US20130261055A1

公开(公告)日：2013-10-03

申请号：US12890626

申请日：2010-09-25

申请人： Andrew V. Schally ,  Marta Zarandi ,  Jozsef L. Varga ,  Ren Zhi Cai

发明人： Andrew V. Schally ,  Marta Zarandi ,  Jozsef L. Varga ,  Ren Zhi Cai

IPC分类号： A61K38/25 ,  A61P35/00 ,  A61K38/22

CPC分类号： A61K38/25 ,  A61K38/00 ,  C07K14/60 ,  C07K14/645

摘要： There is provided a novel series of synthetic analogs of hGH-RH(1-29)NH2 (SEQ ID NO: 96) and hGH-RH(1-30)NH2. Of particular interest are those carrying PhAc, N-Me-Aib, Dca, Ac-Ada, Fer, Ac-Amc, Me-NH-Sub, PhAc-Ada, Ac-Ada-D-Phe, Ac-Ada-Phe, Dca-Ada, Dca-Amc, Nac-Ada, Ada-Ada, or CH3—(CH2)10—CO-Ada, at the N-Terminus and β-Ala, Amc, Apa, Ada, AE2A, AE4P, ε-Lys(α-NH2), Agm, Lys(Oct) or Ahx, at the C-terminus. These analogs inhibit the release of growth hormone from the pituitary in mammals as well as inhibit the proliferation of human cancers, and inhibit the hyperplastic and benign proliferative disorders of various organs, through a direct effect on the cancerous and non-malignant cells. The stronger inhibitory potencies of the new analogs, as compared to previously described ones, result from replacement of various amino acids.

摘要翻译： 提供了hGH-RH（1-29）NH2（SEQ ID NO：96）和hGH-RH（1-30）NH2的新一系列合成类似物。 特别感兴趣的是携带PhAc，N-Me-Aib，Dca，Ac-Ada，Fer，Ac-Amc，Me-NH-Sub，PhAc-Ada，Ac-Ada-D-Phe，Ac-Ada-Phe， Dca-Ada，Dca-Amc，Nac-Ada，Ada-Ada或CH 3 - （CH 2）10 -CO-Ada，在N-末端和β-Ala，Amc，Apa，Ada，AE2A，AE4P， Lys（α-NH2），Agm，Lys（Oct）或Ahx。 这些类似物通过对癌和非恶性细胞的直接作用，抑制哺乳动物垂体中生长激素的释放以及抑制人类癌症的增殖，并抑制各种器官的增生和良性增生性疾病。 与之前描述的相比，新类似物的更强的抑制效力是由于各种氨基酸的替换而产生的。

公开(公告)号：US5942489A

公开(公告)日：1999-08-24

申请号：US642472

申请日：1996-05-03

申请人： Andrew V. Schally ,  Marta Zarandi ,  Katalin Toth

发明人： Andrew V. Schally ,  Marta Zarandi ,  Katalin Toth

IPC分类号： A61K38/04 ,  A61K38/00 ,  A61P35/00 ,  C07K14/60 ,  A61K38/16 ,  A61K38/12 ,  C07K7/00 ,  C07K7/64

CPC分类号： C07K14/60 ,  A61K38/00

摘要： A peptide selected from the group having the formulae:.alpha.) X-R.sup.1 -R.sup.2 -R.sup.3 -R.sup.4 -R.sup.5 -R.sup.6 -Thr-R.sup.8 -R.sup.9 -R.sup.10 -R.sup.11 -R.sup.12 -Val-Leu-R.sup.15 -Gln-Leu-Ser-R.sup.19 -R.sup.20 -R.sup.21 -Leu-Leu-Gln-Asp-Ile-R.sup.27 -R.sup.28 -R.sup.29, wherein X is H, Ac, Aqc, IAc, BrProp, For, Ibu, Nac, 2-Nac, 1- or 2-Npt, 1- or 2-Npr, PhAc, Fpr, or any other aromatic or nonpolar acyl group, R.sup.1 is Tyr, His or Phe(Y), in which Y=H, F, Cl, Br, NO.sub.2, CH.sub.3 or OCH.sub.3, R.sup.2 is D-Arg, D-Cit, D-Har, D-Lys, D-Tic or D-Orn, R.sup.3 is Asp, D-Asp, Ala, D-Ala or Gly, R.sup.4 is Ala, Abu or Gly, R.sup.5 is Ile, Ala or Gly, R.sup.6 is Phe, Tic, Ala, Pro, Tpi, Nal or Phe(Y), in which Y=H, F, Cl, Br, NO.sub.2, NH.sub.2, CH.sub.3 or OCH.sub.3, R.sup.8 is Asn, Gln, Ser, Thr, Val, Leu, Ile, Ala, D-Ala, D-Asn, D-Gln, D-Thr, D-Leu, Abu, D-Abu, Nle, or Alb, R.sup.9 is Ser, R.sup.10 is Tyr or Phe(Y), in which Y=H, F, Cl, Br, NO.sub.2, CH.sub.3 or OCH.sub.3, R.sup.11 is Arg, D-Arg, or Cit, R.sup.12 is Lys, D-Lys, Cit, D-Cit, Orn, D-Orn, Nle or Ala, R.sup.15 is Gly, Ala, Abu or Gln, R.sup.19 is Ala or Abu, R.sup.20 is Arg, D-Arg or Cit, R.sup.21 is Lys, D-Lys, Orn or Cit, R.sup.27 is Met, Nle or Abu, R.sup.28 is Ser, Asn, Ala or Abu, R.sup.29 is Agm, Arg-NH.sub.2, Arg-OH, Cit-NH.sub.2, Cit-OH, Har-NH.sub.2 or Har-OH, and.beta.) X-A.sup.1 -B.sup.2 -A.sup.3 -R.sup.4 -R.sup.5 -R.sup.6 -Thr-A.sup.8 Ser-R.sup.10 -R.sup.11 -B.sup.12 -Val-Leu-R.sup.15 -A.sup.16 -A.sup.17 -Ser-R.sup.19 -B.sup.20 -B.sup.21 -Leu-Leu-Gln-A.sup.26 -Ile-R.sup.27 -R.sup.28 -R.sup.29, wherein a lactam bridge is formed between any one of the pairs of positions 1,2; 2,3; 8,12; 16,20; 17-21; 21,25; 25,29 or both 8,12 and 21,25 positions, and X is H, Ac, Aqc, IAc, BrProp, For, Ibu, Nac, 2-Nac, 1- or 2-Npt, 1- or 2-Npr, PhAc, Fpr, or any other aromatic or nonpolar acyl group, A is Glu, D-Glu, Gln, Asp, D-Asp, Asn, Abu, Leu, Tyr, His, Phe(Y), in which Y=H, F, cl, Br, NO.sub.2, NH.sub.2, CH.sub.3 or OCH.sub.3, Ser, Thr, Val, Ile, Ala, D-Ala, D-Asn, D-Gln, D-Thr, D-Leu, Abu, D-Abu, Nle, or Aib, B is Lys, D-Lys, Arg, D-Arg,Orn, D-Orn, or Agm; R.sup.4 is Ala, Abu or Gly, R.sup.5 is Ile, Ala or Gly, R.sup.6 is Phe, Tic, Tpi, Nal or Phe(Y), in which Y=H, F, Cl, Br, NO.sub.2, NH.sub.2 CH.sub.3 or OCH.sub.3, R.sup.10 is Tyr or Phe(Y), in which Y=H, F, Cl, Br, NO.sub.2, NH.sub.2 CH.sub.3 or OCH.sub.3, R.sup.15 is Gly, Ala, Abu or Gin, R.sup.27 is Met, Nle or Abu, R.sup.28 is Ser, Asn, Asp, Ala or Abu, and pharmaceutically acceptable salts thereof.