公开(公告)号：US5100873A

公开(公告)日：1992-03-31

申请号：US380539

申请日：1989-07-17

申请人： Roberto de Castiglione ,  Mauro Galantino ,  Fabio Corradi ,  Luigia Gozzini ,  Marina Ciomei ,  Isabella Molinari

发明人： Roberto de Castiglione ,  Mauro Galantino ,  Fabio Corradi ,  Luigia Gozzini ,  Marina Ciomei ,  Isabella Molinari

IPC分类号： A61K38/00 ,  A61P35/00 ,  C07K1/02 ,  C07K7/06 ,  C07K7/08

CPC分类号： C07K7/086 ,  A61K38/00

摘要： A peptide of formula (I):A-B-C-D-Gln-Trp-Ala-Val-X-Y-T-W (I)wherein either:(i) A represents a hydrogen atom, a Boc group or an acetyl group, one of B and C represents a pMel or mMel residue, and the other of B and C represents a sigma bond or a Gly, Leu-Gly, E-Leu-Gly or Gln-E-Leu-Gly, E, or E-Gly residue with E=Arg(A), arg(A), Lys(A), lys(A), Orn(A) and orn(A); or(ii) A represents a hydrogen atom;B represents a Glp-Arg-Leu-Gly residue;C represents a pMel or mMel residue;D represents a sigma bond or an Asn or Thr residue;X represents a Gly or ala residue;Y represents a sigma bond or a His(R.sub.1);his(R.sub.1), Phe, phe, Ser, ser, Ala or ala residue,T represents a sigma bond or a Leu, leu, Phe or phe residue;W represents an OH, amino, pentylamino or phenethyl-amino group or a Met-R.sub.2, Leu-R.sub.2, Ile-R.sub.2 or Nle-R.sub.2 residue;R.sub.1 represents a hydrogen atom or a Tos, Dnp or Bzl group; andR.sub.2 represents an amino, hydroxy, methoxy or hydrazino group;and its pharmaceutically acceptable salts are disclosed.

摘要翻译： 式（I）的肽：ABCD-Gln-Trp-Ala-Val-XYTW（I）其中：（i）A表示氢原子，Boc基或乙酰基，B和C之一表示pMel 或mMel残基，B和C中的另一个表示σ键或具有E = Arg（Gly）的Gly，Leu-Gly，E-Leu-Gly或Gln-E-Leu-Gly，E或E-Gly残基 ），arg（A），Lys（A），lys（A），Orn（A）和orn（A）; 或（ii）A表示氢原子; B表示Glp-Arg-Leu-Gly残基; C表示pMel或mMel残基; D表示σ键或Asn或Thr残基; X表示Gly或ala残基; Y表示σ键或His（R1）; 他的（R1），Phe，phe，Ser，ser，Ala或ala残基，T表示σ键或Leu，leu，Phe或phe残基; W表示OH，氨基，戊基氨基或苯乙基 - 氨基或Met-R2，Leu-R2，Ile-R2或Nle-R2残基; R1表示氢原子或Tos，Dnp或Bzl基团; 并且R 2表示氨基，羟基，甲氧基或肼基; 及其药学上可接受的盐。

公开(公告)号：US4491541A

公开(公告)日：1985-01-01

申请号：US542974

申请日：1983-10-18

申请人： Roberto de Castiglione ,  Luigia Gozzini ,  Pier C. Montecucchi ,  Giuseppe Perseo

发明人： Roberto de Castiglione ,  Luigia Gozzini ,  Pier C. Montecucchi ,  Giuseppe Perseo

IPC分类号： A61K38/00 ,  C07K5/078 ,  C07K5/097 ,  C07K5/107 ,  C07K5/117 ,  C07K7/06 ,  C07C103/52

CPC分类号： C07K7/06 ,  C07K5/06173 ,  C07K5/0823 ,  C07K5/1016 ,  C07K5/1024 ,  A61K38/00 ,  Y02P20/55

摘要： A peptide of formula (I):X-A-B-C-Trp-D-YwhereinX represents hydrogen, or a terminal nitrogn protecting group selecting from the group consisting of the acyl, aromatic oxycarbonyl, alkyl, aralkyl and aliphatic oxycarbonyl;A represent a valence bond or a L-.alpha.-amino acid residue;B represent a L-.alpha.-imino acid residue or a L-.alpha.-amino acid;C represent a L-.alpha.-imino acid residue or a neutral L-.alpha.-amino acid residue;D represents a valence bond or a L-.alpha.-amino acid residue; andY represents hydroxy, an amino group or a group of the formula OR, NHR, NR.sub.2 or NH--NH--R', wherein R represents a straight chain, branched chain or cyclic (including fused or bridged ring) alkyl group having up to 11 carbon atoms, optionally being substituted; a phenyl group or an aralkyl group having from 7 to 9 carbon atoms; and R' represents hydrogen, any of the groups which R may represent; a straight chain, branched chain or cyclic aliphatic acyl group having from 1 to 11 carbon atoms, optionally substituted by hydroxy, an amino group or a halogen atom; an aromatic acyl group, optionally substituted by hydroxy, amino, or a halogen atom; a straight chain, branched chain or cyclic aliphatic oxycarbonyl group having from 3 to 11 carbon atoms, or an aromatic oxycarbonyl group.

摘要翻译： 式（I）的肽：X-A-B-C-Trp-D-Y，其中X表示氢，或末端硝基保护基选自酰基，芳族氧羰基，烷基，芳烷基和脂族氧基羰基; A代表价键或L-α-氨基酸残基; B代表L-α-亚氨基酸残基或L-α-氨基酸; C代表L-α-亚氨基酸残基或中性L-α-氨基酸残基; D表示价键或L-α-氨基酸残基; 并且Y表示羟基，氨基或式OR的基团，NHR，NR2或NH-NH-R'，其中R表示直链，支链或环状（包括稠合或桥接的环）烷基，其具有至多 11个碳原子，任选被取代; 具有7至9个碳原子的苯基或芳烷基; 并且R'表示氢，R可以表示的任何基团; 具有1至11个碳原子的直链，支链或环状脂族酰基，任选被羟基，氨基或卤素原子取代; 任选被羟基，氨基或卤素原子取代的芳族酰基; 具有3至11个碳原子的直链，支链或环状脂族氧基羰基或芳族氧羰基。

公开(公告)号：US4350627A

公开(公告)日：1982-09-21

申请号：US212586

申请日：1980-12-03

申请人： Roberto de Castiglione ,  Fiorenzo Faoro ,  Giuseppe Perseo ,  Silvano Piani ,  Francesco Santangelo

发明人： Roberto de Castiglione ,  Fiorenzo Faoro ,  Giuseppe Perseo ,  Silvano Piani ,  Francesco Santangelo

IPC分类号： A61K38/00 ,  C07K5/107 ,  C07K14/665 ,  C07C103/52 ,  A61K37/00

CPC分类号： C07K14/665 ,  C07K5/1016 ,  A61K38/00 ,  Y02P20/55 ,  Y10S514/809

摘要： There is disclosed biologically active peptides of the formula ##STR1## where X is a hydrogen atom, an N-terminus protecting group (any of an acyl-type protecting group, an aromatic urethane-type protecting group, an alkyl-type protecting group, or an alkyl urethane type protecting group), or a residue of a natural L-amino acid or a dipeptide formed of two natural L-amino acids, wherein the free amino group may be replaced by any of the foregoing N-terminus protecting groups;Y is a hydrogen atom or a protecting group for the phenolic hydroxyl group of tyrosine;A is a D-amino acid residue with a lower (thio) alkyl side chain;B is a neutral L-amino acid residue, a glycine residue, or an N-methyl amino acid residue;C is a direct bond or an amino acid or di-or tripeptide residue; andW is OH, OR, NH.sub.2, NHR, N(R).sub.2, NH-NH.sub.2, where R is an alkyl, cycloalkyl or aralkyl group of 1 to 7 carbon atoms or NHNHR' where R' is a hydrogen atom, linear or branched alkyl, cycloalkyl; alkenyl, a linear or branched or cyclic aliphatic urethane-type group, an aromatic urethane-type group normally used in polypeptide chemistry, a residue of an .alpha.-amino; .alpha.-imino, or .beta.-amino acid, or a di-or tripeptide residue, where the -NHR' bond is an amidic linkage and the amino group is free or protected by an N-terminus protecting group. The peptides have central nervous system activity and are useful as analgesics, psychotics, and neuroendocrinologicals.

摘要翻译： 公开了式（I）的生物活性肽，其中X是氢原子，N末端保护基（酰基型保护基，芳族氨基甲酸酯型保护基，烷基型 保护基或烷基氨基甲酸酯型保护基）或由两种天然L-氨基酸形成的天然L-氨基酸或二肽的残基，其中游离氨基可以被任何前述N-末端替代 保护团体 Y是氢原子或酪氨酸酚羟基的保护基; A是具有低级（硫代）烷基侧链的D-氨基酸残基; B是中性L-氨基酸残基，甘氨酸残基或N-甲基氨基酸残基; C是直接键或氨基酸或二 - 或三肽残基; 并且W是OH，OR，NH 2，NHR，N（R）2，NH-NH 2，其中R是1至7个碳原子的烷基，环烷基或芳烷基或NHNHR'，其中R'是氢原子，直链或 支链烷基，环烷基; 链烯基，直链或支链或环状脂族氨基甲酸酯基，通常用于多肽化学的芳族氨基甲酸酯基，α-氨基的残基; α-亚氨基或β-氨基酸，或二 - 或三肽残基，其中-NHR'键是酰胺键，氨基由N-末端保护基游离或保护。 肽具有中枢神经系统活性，可用作止痛药，精神药物和神经内分泌学。

公开(公告)号：US4567162A

公开(公告)日：1986-01-28

申请号：US624820

申请日：1984-06-26

申请人： Roberto de Castiglione ,  Giuseppe Perseo ,  Mauro Gigli ,  Barbara Hecht

发明人： Roberto de Castiglione ,  Giuseppe Perseo ,  Mauro Gigli ,  Barbara Hecht

IPC分类号： A23K1/16 ,  A23K1/18 ,  A61K38/00 ,  A61P43/00 ,  C07K1/113 ,  C07K7/06 ,  A61K37/00

CPC分类号： C07K7/06 ,  A23K20/147 ,  A23K50/30 ,  A61K38/00 ,  Y02P20/55 ,  Y10S930/12

摘要： There are provided peptides of the formulaX-Val-Pro-Leu-Gly-Trp-A-Ywherein X represents a hydrogen atom or a terminal nitrogen protecting group, A represents a neutral L-.alpha.-amino acid residue and Y represents OH, NH.sub.2 or a group of the formula OR, NHR, NR.sub.2 or NHNHR' wherein R represents a C.sub.1 -C.sub.11 alkyl group optionally substituted, a C.sub.7 -C.sub.14 aralkyl or a phenyl group and R' represents H, any of the groups which R may represent or a protecting group. Pharmaceutically or veterinarily acceptable salt of these peptides are also provided, as are pharmaceutical or veterinary compositions containing peptides or their salts. The peptides which can be prepared by classical solution synthesis, display useful activity on the central nervous system and are active as growth promotors.

摘要翻译： 提供式X-Val-Pro-Leu-Gly-Trp-AY的肽，其中X表示氢原子或末端氮保护基，A表示中性的L-α-氨基酸残基，Y表示OH，NH 2 或式OR，NHR，NR2或NHNHR'的基团，其中R表示任选取代的C 1 -C 11烷基，C 7 -C 14芳烷基或苯基，R'表示H，R可以表示的任何基团或 一个保护组。 还提供这些肽的药学上或兽医学上可接受的盐，以及含有肽或其盐的药物或兽医组合物。 可以通过经典溶液合成制备的肽显示对中枢神经系统的有用活性，并且作为生长促进剂是活性的。

公开(公告)号：US4716228A

公开(公告)日：1987-12-29

申请号：US839935

申请日：1986-03-17

申请人： Ugo Scarponi ,  Anna M. Lazzarini ,  Daniela Toti ,  Roberto de Castiglione

发明人： Ugo Scarponi ,  Anna M. Lazzarini ,  Daniela Toti ,  Roberto de Castiglione

IPC分类号： A61K31/425 ,  A61P1/04 ,  C07D513/04 ,  A61K31/55 ,  C07D417/04

CPC分类号： C07D513/04

摘要： A process for preparing compounds of the formula I ##STR1## wherein either (i) each of R.sub.1 and R.sub.2 independently represents H or an organic group, or (ii) NR.sub.1 R.sub.2 is a heterocyclic ring or (iii) R.sub.2 is H and R.sub.1 is ##STR2## wherein each of R.sub.6 and R.sub.7 independently represents H or an organic group, m is 1 or 2, n is 0-3, X is O, S, NH, NR.sub.8, CHNO.sub.2 or CHSO.sub.2 R.sub.4 wherein R.sub.8 and R.sub.4 are organic groups and R.sub.3 represents an organic group is characterized by the following reaction sequence: ##STR3## There are also provided new compounds of the formula I wherein n is 0 and m is 2 and pharmaceutical compositions containing them. These compounds and their pharmaceutically acceptable acid addition salts are active as anti-ulcer agents.

摘要翻译： 一种制备式I化合物的方法，其中（i）R 1和R 2各自独立地表示H或有机基团，或（ii）NR 1 R 2为杂环，或（iii）R 2为H和 R 1为，其中R 6和R 7各自独立地表示H或有机基团，m为1或2，n为0-3，X为O，S，NH，NR 8，CHNO 2或CHSO 2 R 4，其中R 8和R 4为有机基团 基团和R 3表示有机基团，其特征在于以下反应顺序：还提供了新的式I化合物，其中n为0且m为2，以及含有它们的药物组合物。 这些化合物及其药学上可接受的酸加成盐作为抗溃疡剂是有活性的。

公开(公告)号：US4624956A

公开(公告)日：1986-11-25

申请号：US680566

申请日：1984-12-11

申请人： Anna M. Lazzarini ,  Ugo Scarponi ,  Roberto de Castiglione ,  Roberto Ceserani ,  Renato Castello ,  Fabrizio Vaghi ,  Daniela Toti

发明人： Anna M. Lazzarini ,  Ugo Scarponi ,  Roberto de Castiglione ,  Roberto Ceserani ,  Renato Castello ,  Fabrizio Vaghi ,  Daniela Toti

IPC分类号： A61K31/435 ,  A61P1/04 ,  A61P43/00 ,  C07D513/04 ,  A61K31/445

CPC分类号： C07D513/04

摘要： A compound of formula I: ##STR1## wherein either (i) each of R.sub.1 and R.sub.2 independently represents a hydrogen atom or an organic group, or (ii) R.sub.1 and R.sub.2 linked together form a heterocyclic ring or (iii) R.sub.2 is hydrogen and R.sub.1 is ##STR2## wherein each of R.sub.6 and R.sub.7 independently represents hydrogen or an organic group, n is 0-3, X is O, S, NH, NR.sub.8, CHNO.sub.2 or CHSO.sub.2 R.sub.4, wherein R.sub.8 and R.sub.4 are organic groups and R.sub.3 represents an organic group. The compound of formula I is effective as an anti-ulcer agent and is highly effective as a histamine H.sub.2 -receptor antagonist.

摘要翻译： 式I化合物：其中（i）R 1和R 2各自独立地表示氢原子或有机基团，或（ii）连接在一起的R 1和R 2形成杂环，或（iii）R 2是氢和 R1为，其中R6和R7各自独立地表示氢或有机基团，n为0-3，X为O，S，NH，NR8，CHNO2或CHSO2R4，其中R8和R4为有机基团，R3表示 有机组。 式I化合物作为抗溃疡剂是有效的，作为组胺H 2受体拮抗剂是非常有效的。

公开(公告)号：US4474765A

公开(公告)日：1984-10-02

申请号：US481298

申请日：1983-04-01

申请人： Roberto de Castiglione ,  Giuseppe Perseo ,  Francesco Santangelo

发明人： Roberto de Castiglione ,  Giuseppe Perseo ,  Francesco Santangelo

IPC分类号： C07K7/08 ,  A61K38/00 ,  A61K38/04 ,  C07K7/23 ,  C07K14/575 ,  A61K37/00 ,  C07C103/52

CPC分类号： C07K14/57509 ,  A61K38/00 ,  Y02P20/55

摘要： Peptides of the formulaX-A-Pro-Pro-Ile-Ser-B-C-Leu-D-E-F-G-WwhereinX is H, a terminal N atom protecting group of acyl, aromatic urethane, aliphatic urethane, alkyl or aralkyl type, or a residue of a natural L-amino acid, the free amino group of the residue optionally being protected by a terminal N atom protecting group as aforesaid;A is a L-amino acid residue or a glycine residue;B is a neutral L-amino acid residue; C is a neutral L-amino acid residue or an acidic L-amino acid residue;D is a L-amino acid residue which contains in the side chain an alcoholic hydroxyl group; the latter may be free or protected by a usual protecting group for the hydroxy function, said protecting group being t-butyl, trityl, benzyl, 2,4-dichloro-benzyl, benzyloxycarbonyl, 2-bromobenzyloxycarbonyl t-butoxycarbonyl or lower acyl;E is a valence bond or a neutral L-amino acid residue;F is a valence bond or a L-amino acid residue;G is a valence bond or a neutral L-amino acid residue;W is OH, NH.sub.2, OR, NHR, NR.sub.2 or NH--NH--R';R is a straight chain, branched chain or cyclic (including fused or bridged ring), substituted or unsubstituted C.sub.1 C.sub.11 alkyl group, phenyl, or C.sub.6 --C.sub.8 aralkyl;R' is H, any value which R may have, a straight chain, branched chain or cyclic aliphatic C.sub.1 -C.sub.11 acyl group (optionally substituted by OH, NH.sub.2, or a halogen atom), a C.sub.3 -C.sub.8 alkenyl group, an aromatic acyl group similarly optionally substituted, a straight chain, branched chain or cyclic aliphatic C.sub.3 -C.sub.11 urethane type group or an aromatic urethane type group.Phamaceutically acceptable salts of these peptides are also provided, as are pharmaceutical compositions containing peptides or their salts. The peptides can be prepared by classical solution synthesis or by solid phase synthesis on polymeric supports.

摘要翻译： 式XA-Pro-Pro-Ile-Ser-BC-Leu-DEFGW的肽，其中X是H，酰基的末端N原子保护基，芳族氨基甲酸酯，脂肪族氨基甲酸酯，烷基或芳烷基，或天然的残基 L-氨基酸，残留物的游离氨基任选被如上所述的末端N原子保护基保护; A是L-氨基酸残基或甘氨酸残基; B是中性L-氨基酸残基; C是中性L-氨基酸残基或酸性L-氨基酸残基; D是在侧链中含有醇羟基的L-氨基酸残基; 所述保护基为叔丁基，三苯甲基，苄基，2,4-二氯苄基，苄氧羰基，2-溴苄氧基羰基，叔丁氧羰基或低级酰基; E是价键或中性L-氨基酸残基; F是价键或L-氨基酸残基; G是价键或中性L-氨基酸残基; W是OH，NH 2，OR，NHR，NR 2或NH-NH-R'; R是直链，支链或环状（包括稠合或桥连的环），取代或未取代的C 1 -C 11烷基，苯基或C 6 -C 8芳烷基; R'是H，R可以具有的任何值，直链，支链或环状脂肪族C 1 -C 11酰基（任选被OH，NH 2或卤素原子取代），C 3 -C 8烯基，芳香酰基 类似地任选取代的基团，直链，支链或环状脂族C 3 -C 11氨基甲酸酯型基团或芳族氨基甲酸酯基团。 还提供了这些肽的药学上可接受的盐，以及含有肽或其盐的药物组合物。 肽可以通过经典溶液合成或通过聚合物载体上的固相合成来制备。