Abstract: 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 ?-Ala, Amc, Apa, Ada, AE2A, AE4P, ?-Lys(?-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.

Abstract: Agonists of growth hormone releasing hormone promote islet graft growth and proliferation in patients. Methods of treating patients comprise the use of these agonists.

Abstract: Whether the growth hormone (GH)/Insulin-like growth factor 1(IGF-I) axis exerts cardioprotective effects remains controversial; and the underlying mechanism(s) for such actions are unclear. Here we tested the hypothesis that growth-hormone releasing hormone (GHRH) directly activates cellular reparative mechanisms within the injured heart, in a GH/IGF-I independent fashion. Following experimental myocardial infarction (MI), rats were randomly assigned to receive, during a 4 week period, either placebo (n=14), rat recombinant GH (rrGH, n=8) or JI-38 (n=8; 50 ?g/Kg/day), a potent GHRH-agonist. JI-38 did not elevate serum levels of GH or IGF-I, but markedly attenuated the degree of cardiac functional decline and remodeling after injury. In contrast, GH administration markedly elevated body weight, heart weight, circulating GH and IGF-I, but did not offset the decline in cardiac structure and function.

Abstract: Agonists of growth hormone releasing hormone promote islet graft growth and proliferation in patients. Methods of treating patients comprise the use of these agonists.

Abstract: There are provided means for suppressing the Reactive Oxidant Species (ROS) of certain cells by the administration of GHRH antagonists. The therapeutic applications of the anti-oxidative action of GH-RH antagonists relate to the redox status of certain cells, including but not limited to cancer cells, reducing the metabolism of reactive oxygen and nitrogen species. This antioxidant activity of GHRH antagonists is employable in the treatment of diseases in which their pathogenesis is related to increased cellular level of oxidative stress.

Abstract: 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.

Abstract: 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.

Abstract: The present invention deals with LHRH analogs which contain cytotoxic moieties, have influence on the release of gonadotropins from the pituitary in mammals (possess high agonistic or antagonistic activity) and have antineoplastic effect.

Abstract: This invention is in the field of the chemistry of targeting anticancer anthracycline derivatives. More particularly, it concerns doxorubicin (DOX) or its daunosamine modified derivatives (DM-DOX) linked covalently to analogs of peptide hormones such as LH-RH, bombesin and somatostatin. These covalent conjugates are targeted to various tumors bearing receptors for the peptide hormone analogs. The compounds of this invention are represented by General Formula Q14—O—R—P wherein Q has the general formula wherein: Q14 signifies a Q moiety with a side chain at the 14 position, R— is H or —C(O)—(CH2)n—C(O)— and n=0-7, R′ is NH2 or an aromatic, saturated or partially saturated 5 or 6 membered heterocyclic compounds having at least one ring nitrogen and optionally having a butadiene moiety bonded to adjacent carbon atoms of said ring to form a bicyclic system; P is H or a peptide moiety, suitably an LHRH, somatostatin or bombesin analogs.

Abstract: There is provided a novel series of synthetic analogs of hGH-RH(1-29) NH.sub.2. 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.

Abstract: 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.

Abstract: This invention is in the field of the chemistry of targeting anticancer anthracycline derivatives. More particularly, it concerns doxorubicin (DOX) or its daunosamine modified derivatives (DM-DOX) linked covalently to analogs of peptide hormones such as LH-RH, bombesin and somatostatin. These covalent conjugates are targeted to various tumors bearing receptors for the peptide hormone analogs. The compounds of this invention are represented by General Formula Q.sup.14 --O--R--P wherein Q has the general formula ##STR1## wherein: Q.sup.14 signifies a Q moiety with a side chain at the 14 position, R-- is H or --C(O)--(CH.sub.2).sub.n --C(O)-- and n=0-7, R' is NH.sub.2 or an aromatic, saturated or partially saturated 5 or 6 membered heterocyclic compounds having at least one ring nitrogen and optionally having a butadiene moiety bonded to adjacent carbon atoms of said ring to form a bicyclic system; P is H or a peptide moiety, suitably an LHRH, somatostatin or bombesin analogs. Nevertheless where R' is NH.sub.

Abstract: Synthetic peptides which have the sequence:Q.sup.1 -CO -Ala.sup.2 -Asp.sup.3 -Ala.sup.4 -Ile.sup.5 -Phe.sup.6 -Thr.sup.7 -R.sup.8 -Ser.sup.9 -Tyr.sup.10 -Arg.sup.11 -R.sup.12 -Val.sup.13 -Leu.sup.14 -R.sup.15 -Gln.sup.16 -Leu.sup.17 -Ser.sup.18 -Ala.sup.19 -Arg.sup.20 -R.sup.21 -Leu.sup.22 -Leu.sup.23 -Gln.sup.24 -Asp.sup.25 -Ile.sup.26 -R.sup.27 -R.sup.28 -NH-Q.sup.2wherein Q.sup.1 is an omega or alpha-omega substituted alkyl of the structure: ##STR1## where: ?.phi.! is phenyl; Y is H, --NH.sub.2, CH.sub.3 CONH--or CH.sub.3 NH--; Z is H or CH.sub.3 ; m is 1 or 2; n is 0, 1 or 2; R.sup.8 is Asn, Ser, Gln or Thr; R.sup.12 is Lys or Orn; R.sup.15 is Gly, Ala, or Abu;R.sup.21 is Lys or Orn; R.sup.27 is Met or Nle; R.sup.28 is Ser or Asp; and Q.sup.2 is a lower omega-guanidino-alkyl group having a formula: --(CH.sub.2).sub.p --NH--C(NH.sub.2).dbd.NH wherein p is 2-6, and the pharmaceutically acceptable addition salts thereof with the pharmaceutically acceptable organic or inorganic bases or acids.

Abstract: Synthetic analogues of hGH-RH(1-29)NH.sub.2 having substitutions of various amino acids and acylated at the N-terminus, and exhibiting prolonged antagonistic duration. Embodiments include analogues of the formula: ##STR1## wherein X is nil, H, Ac, IAc, BrProp, Ibu, Nac, 2-Nac, 1- or 2-Npt, 1- or 2-Npr or Aqc; R.sup.1 is Tyr, His, Glu or Glt; R.sup.2 is D-Arg, D-Cit, D-Har, D-Lys or D-Orn; R.sup.3 is Asp, Ala or Gly; R.sup.4 is Ala or Gly; R.sup.5 is Ile, Ala or Gly; R.sup.6 is Phe, Ala, Pro, Tpi, Nal or Phe(Y), in which Y is F, Cl, Br, NO.sub.2, CH.sub.3 or OCH.sub.3 ; R.sup.8 is Asn, Ser, Val, Ile, Ala, Abu, Nle, or Aib; R.sup.11 is Arg, D-Arg or Cit; R.sup.12 is Lys, D-Lys, Cit 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 or Cit; R.sup.27 is Met, Nle or Abu; R.sup.28 is Ser, Asn, Asp 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; provided that when R.sup.

Abstract: Pseudopeptides comprising a peptide of formula I:X-A.sup.1 -A.sup.2 -Trp-Ala-Val-Gly-His-Leu-.sub.psi -A.sup.9 -Qwherein X is hydrogen, a single bond linking the alpha amino group of A.sup.1 to the gamma carboxyl moiety on the 3-priopionyl moiety of A.sup.2 when A.sup.2 is Glu, or a group of formula R.sup.1 CO-- wherein R.sup.1 is selected from the groups consisting ofa) hydrogen, C.sub.1-10 alkyl, phenyl or phenyl-C.sub.1-10 -alkyl, p-HI-phenyl, p-HI-phenyl-C.sub.1-10 -alkyl, naphthyl, naphthyl-C.sub.1-10 -alkyl, indolyl, indolyl-C.sub.1-10 -alkyl, pyridyl, pyridyl-C.sub.1-10 -alkyl, thienyl, thienyl-C.sub.1-10 -alkyl, cyclohexyl or cyclohexyl-C.sub.1-10 -alkyl, where HI=F, Cl, Br, OH, CH.sub.3 or OCH.sub.3 ;b) N(R.sup.2)(R.sup.3)--, wherein R.sup.2 is hydrogen, C.sub.1-10 alkyl, phenyl or phenyl-C.sub.1-10 -alkyl, R.sup.3 is hydrogen or C.sub.1-10 alkyl; c) R.sup.4 O--, wherein R.sup.4 is C.sub.1-10 alkyl, phenyl or phenyl-.sub.1-10 -alkyl; A.sup.

Abstract: The present invention deals with LHRH analogues which contain cytotoxic moieties and have influence on the release of gonadotropins from the pituitary gland of mammals, including humans. The compounds of this invention are represented by the formula:X--R.sup.1 --R.sup.2 --R.sup.3 -Ser-R.sup.5 --R.sup.6 (Q)-Leu-Arg-Pro-R.sup.10 --NH.sub.2whereinR.sup.1 is pGlu, Pro, D-Nal(2), or D-Phe(4Cl),R.sup.2 is His or D-Phe(4Cl),R.sup.3 is Trp, D-Trp or D-Pal(3),R.sup.5 is Tyr or Arg,R.sup.6 is D-Phe or R*.sup.6, where R*.sup.6 is D-Orn, D-Lys or D-Phe(NH.sub.2),R.sup.10 is Gly or D-Ala,X is hydrogen, a lower alkanoyl group of 2-5 carbon atoms or carbamyl,Q is bis-(2-chloroethyl)amino group provided that R.sup.6 is D-Phe,where R.sup.6 is R*.sup.6,Q is a complexed metal-containing acyl group having the formula: ##STR1## wherein Q' is Pt(Y).sub.

Abstract: The novel pseudo polypeptides of this invention are potent bombesin antagonists. There are provided processes for their production, pharmaceutical compositions comprising said polypeptides and their use as pharmaceutically active agents. More particularly the present invention provides pseudopeptides comprising a nonapeptide moiety of formula I:X-A.sup.1 -A.sup.2 -A.sup.3 -A.sup.4 -A.sup.5 -A.sup.6 -A.sup.7 -A.sup.8 -.sub.psi -A.sup.9 -Qwherein Q is NH.sub.2 or OQ.sup.1 where Q.sup.1 is hydrogen, C.sub.1-10 alkyl, phenyl or phenyl-C.sub.7-10 alkyl; X is hydrogen or a single bond linking to A.sup.2 the acyl residue of an organic acid, or a group of formula R.sup.1 CO-- wherein (1) R.sup.1 is hydrogen, C.sub.1-10 alkyl, phenyl or phenyl-C.sub.7-10 -alkyl; (2) R.sup.1 CO-- is (a) R.sup.2 N(R.sup.3)--CO-- wherein R.sup.2 is hydrogen, C.sub.1-10 alkyl, phenyl or C.sub.7-10 phenyl-C.sub.7-10 -alkyl, R.sup.3 is hydrogen or C.sub.1-10 alkyl; (b) R.sup.4 --O--CO-- wherein R.sup.4 is C.sub.

Abstract: The present invention deals with LHRH antagonists which possess improved water solubility and while having the high antagonist potency of the basic peptides, are free of the edematogenic effects. These compounds are highly potent in inhibiting the release of gonadotropins from the pituitary gland in mammals, including humans.The compounds of this invention are represented by the formulaX--R.sup.1 --R.sup.2 --R.sup.3 --Ser--Tyr--R.sup.6 --Leu--Arg--Pro--R.sup.10 --NH.sub.2whereinX is an acyl group derived from straight or branched chain aliphatic or alicyclic carboxylic acids having from 1 to 7 carbon atoms, or H.sub.2 N--CO,R.sup.1 is D-- or L--Pro, D-- or L--.DELTA..sup.3 --Pro, D--Phe, D--Phe(4--H1), D--Ser, D--Thr, D--Ala, D--Nal(1) or D--Nal (2),R.sup.2 is D--Phe or D--Phe(4--C1)R.sup.3 is D--Trp, D--Phe, D--Pal(3), D--Nal(1) or D--Nal(2),R.sup.6 is D--Cit, D--Hci, D--Cit(Q) or D--Hci(Q) andR.sup.

Abstract: Disclosed herein are analogues of the luteinizing hormone-releasing hormone (LH-RH), which are potent antagonists of LH-RH. These peptides inhibit the release of gonadotropins from the pituitary in mammals, including humans and possess antitumor activity.Formula I represents peptides which are within the scope of this invention:X--R.sup.1 --R.sup.2 --R.sup.3 --Ser--R.sup.5 --R.sup.6 (AY.sub.2)--Leu--Arg--Pro--D--Ala--NH.sub.2 Iand the pharmaceutically acceptable salts thereof, whereinR.sup.1 is D-Phe, D-Phe(4Cl), D-Nal(1) or D-Nal(2),R.sup.2 is D-Phe or D-Phe(4HI),R.sup.3 is D-Trp, D-Phe, D-Phe(4HI), D-Nal(1), D-Nal(2) or D-Pal(3),R.sup.5 is Tyr or Arg,R.sup.6 is D-Lys or D-Orn,HI is fluoro, chloro or bromoX is a lower alkanoyl group of 2-5 carbon atoms,A is a diaminoacyl residue having the formula ##STR1## where m is 0 or 1,n is 0 or 1,Y is Y.sup.1 or Y.sup.2, whereinY.sup.

Abstract: Human pancreatic GRF (hpGRF), rat hypothalamic GRF (rGRF) and porcine hypothalamic GRF (pGRF) have been earlier characterized and synthesized. 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: ##STR1## wherein Q.sup.1 is an omega or alpha-omega substituted alkyl,Q.sup.2 is a lower omega-quanidino-alkyl group.R.sub.2 is Ala, D-Ala, or D-N-Methyl-AlaR.sub.3 is Asp, D-Asp, Glu, or D-GluR.sub.8 is Asn, D-Asn, Ser, or D-SerR.sub.10 is Tyr or D-TyrR.sub.12 is Lys, D-Lys Arg or OrnR.sub.13 is Val or IleR.sub.14 is Leu or D-LeuR.sub.15 is Gly, N-Methyl-Gly, or D-AlaR.sub.17 is Leu or D-LeuR.sub.18 is Tyr or SerR.sub.23 is Leu or D-LeuR.sub.24 is Gln or HisR.sub.25 is Asp, D-Asp, Glu, or D-GluR.sub.27 is Met, D-Met, Ala, Nle, Ile, Val, Nva, LeuR.sub.