公开(公告)号：US07973044B2

公开(公告)日：2011-07-05

申请号：US12645154

申请日：2009-12-22

Applicant: Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Susan Ashwell ,  Gregory S. Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren B. Dressen ,  Francine S. Grant ,  Christopher Semko ,  Ying-Zi Xu

Inventor： Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Susan Ashwell ,  Gregory S. Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren B. Dressen ,  Francine S. Grant ,  Christopher Semko ,  Ying-Zi Xu

IPC: A01N43/54 ,  C07D239/42

CPC classification number: A61K31/425 ,  A61K31/41 ,  A61K31/427 ,  A61K31/433 ,  A61K31/44 ,  A61K31/4439 ,  A61K31/445 ,  A61K31/495 ,  A61K31/496 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/50 ,  A61K31/505 ,  A61K31/506 ,  A61K31/53 ,  A61K31/535 ,  A61K31/54 ,  C07D211/58 ,  C07D213/74 ,  C07D213/76 ,  C07D233/88 ,  C07D239/32 ,  C07D239/42 ,  C07D239/47 ,  C07D239/48 ,  C07D239/52 ,  C07D241/20 ,  C07D249/06 ,  C07D251/18 ,  C07D251/48 ,  C07D251/50 ,  C07D251/52 ,  C07D251/54 ,  C07D257/06 ,  C07D285/06 ,  C07D285/10 ,  C07D333/36 ,  C07D333/48 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/04 ,  C07D413/12 ,  C07D417/12 ,  Y02A50/463 ,  A61K2300/00

Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

公开(公告)号：US07745454B2

公开(公告)日：2010-06-29

申请号：US10936070

申请日：2004-09-07

Applicant: Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Susan Ashwell ,  Gregory S. Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren B. Dressen ,  Francine S. Farouz ,  Christopher M. Semko ,  Ying-Zi Xu

Inventor： Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Susan Ashwell ,  Gregory S. Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren B. Dressen ,  Francine S. Farouz ,  Christopher M. Semko ,  Ying-Zi Xu

IPC: A61K31/505 ,  A61K31/515 ,  C07D239/22 ,  C07D239/42 ,  A61P19/02 ,  A61P11/06 ,  A61P37/08

CPC classification number: C07D401/12 ,  C07D239/48 ,  C07D239/52 ,  C07D417/12

Abstract: Disclosed are certain alpha amino acid compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract translation: 公开了结合VLA-4的某些α氨基酸化合物。 这些化合物中的某些也抑制白细胞粘附，特别是由VLA-4介导的白细胞粘附。 这样的化合物可用于治疗哺乳动物患者，例如人类例如哮喘，阿尔茨海默氏病，动脉粥样硬化，艾滋病痴呆，糖尿病，炎性肠病，类风湿性关节炎，组织移植，肿瘤转移和心肌缺血等炎性疾病。 化合物也可以用于治疗炎性脑疾病如多发性硬化症。

公开(公告)号：US20080182850A1

公开(公告)日：2008-07-31

申请号：US11873358

申请日：2007-10-16

Applicant: Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Susan Ashwell ,  Gregory S. Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren B. Dressen ,  Francine S. Grant ,  Christopher Semko ,  Ying-Zi Xu ,  Frank Stappenbeck

Inventor： Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Susan Ashwell ,  Gregory S. Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren B. Dressen ,  Francine S. Grant ,  Christopher Semko ,  Ying-Zi Xu ,  Frank Stappenbeck

IPC: A61K31/41 ,  C07D403/02 ,  A61K31/435 ,  A61K31/501 ,  A61K31/504

CPC classification number: C07D239/48 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14 ,  C07D417/14

Abstract: Disclosed are certain 3-(heteroaryl)alanine derivatives which bind VLA-4 and inhibit leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract translation: 公开了结合VLA-4并抑制由VLA-4介导的白细胞粘附的某些3-（杂芳基）丙氨酸衍生物。 这样的化合物可用于治疗哺乳动物患者，例如人类例如哮喘，阿尔茨海默氏病，动脉粥样硬化，艾滋病痴呆，糖尿病，炎性肠病，类风湿性关节炎，组织移植，肿瘤转移和心肌缺血等炎性疾病。 化合物也可以用于治疗炎性脑疾病如多发性硬化症。

公开(公告)号：US20050203093A1

公开(公告)日：2005-09-15

申请号：US11033079

申请日：2005-01-10

Applicant: Andrei Konradi ,  Michael Pleiss ,  Eugene Thorsett ,  Susan Ashwell ,  Gregory Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren Dressen ,  Francine Grant ,  Christopher Semko ,  Ying-Zi Xu

Inventor： Andrei Konradi ,  Michael Pleiss ,  Eugene Thorsett ,  Susan Ashwell ,  Gregory Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren Dressen ,  Francine Grant ,  Christopher Semko ,  Ying-Zi Xu

IPC: C07D239/42 ,  A61K31/33 ,  A61K31/38 ,  A61K31/381 ,  A61K31/41 ,  A61K31/415 ,  A61K31/425 ,  A61K31/427 ,  A61K31/433 ,  A61K31/435 ,  A61K31/44 ,  A61K31/4439 ,  A61K31/445 ,  A61K31/4468 ,  A61K31/495 ,  A61K31/496 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/50 ,  A61K31/505 ,  A61K31/506 ,  A61K31/53 ,  A61K31/535 ,  A61K31/54 ,  A61K38/00 ,  A61P1/00 ,  A61P3/10 ,  A61P7/00 ,  A61P7/02 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P13/12 ,  A61P17/00 ,  A61P17/06 ,  A61P25/00 ,  A61P25/28 ,  A61P27/02 ,  A61P29/00 ,  A61P31/04 ,  A61P31/18 ,  A61P35/00 ,  A61P35/04 ,  A61P37/00 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D20060101 ,  C07D211/58 ,  C07D213/74 ,  C07D213/76 ,  C07D231/38 ,  C07D233/66 ,  C07D233/88 ,  C07D237/02 ,  C07D239/02 ,  C07D239/46 ,  C07D239/48 ,  C07D239/52 ,  C07D241/20 ,  C07D249/06 ,  C07D251/18 ,  C07D251/48 ,  C07D251/50 ,  C07D251/52 ,  C07D251/54 ,  C07D257/06 ,  C07D285/10 ,  C07D295/22 ,  C07D333/36 ,  C07D333/48 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D521/00

CPC classification number: A61K31/425 ,  A61K31/41 ,  A61K31/427 ,  A61K31/433 ,  A61K31/44 ,  A61K31/4439 ,  A61K31/445 ,  A61K31/495 ,  A61K31/496 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/50 ,  A61K31/505 ,  A61K31/506 ,  A61K31/53 ,  A61K31/535 ,  A61K31/54 ,  C07D211/58 ,  C07D213/74 ,  C07D213/76 ,  C07D233/88 ,  C07D239/32 ,  C07D239/42 ,  C07D239/47 ,  C07D239/48 ,  C07D239/52 ,  C07D241/20 ,  C07D249/06 ,  C07D251/18 ,  C07D251/48 ,  C07D251/50 ,  C07D251/52 ,  C07D251/54 ,  C07D257/06 ,  C07D285/06 ,  C07D285/10 ,  C07D333/36 ,  C07D333/48 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/04 ,  C07D413/12 ,  C07D417/12 ,  Y02A50/463 ,  A61K2300/00

Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

公开(公告)号：US06900179B2

公开(公告)日：2005-05-31

申请号：US09987619

申请日：2001-11-15

Applicant: Eugene D. Thorsett ,  Christopher M. Semko ,  Dimitrios Sarantakis ,  Michael A. Pleiss ,  Anthony Kreft ,  Andrei W. Konradi ,  Francine S. Grant ,  Darren B. Dressen ,  Susan Ashwell ,  Reinhardt Bernhard Baudy ,  Louis John Lombardo

Inventor： Eugene D. Thorsett ,  Christopher M. Semko ,  Dimitrios Sarantakis ,  Michael A. Pleiss ,  Anthony Kreft ,  Andrei W. Konradi ,  Francine S. Grant ,  Darren B. Dressen ,  Susan Ashwell ,  Reinhardt Bernhard Baudy ,  Louis John Lombardo

IPC: A61K31/397 ,  A61K31/4015 ,  A61K31/404 ,  A61K31/495 ,  A61K31/54 ,  A61K38/00 ,  C07K5/02 ,  C07K5/06 ,  C07K5/078

CPC classification number: A61K31/397 ,  A61K31/4015 ,  A61K31/404 ,  A61K31/495 ,  A61K31/54 ,  A61K38/00 ,  C07K5/0215 ,  C07K5/06026 ,  C07K5/06139 ,  C07K5/06165 ,  C07K5/06191

Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract translation: 公开了结合VLA-4的化合物。 这些化合物中的某些也抑制白细胞粘附，特别是由VLA-4介导的白细胞粘附。 这样的化合物可用于治疗哺乳动物患者（例如人，例如哮喘，阿尔茨海默病，动脉粥样硬化，AIDS痴呆，糖尿病，炎性肠病，类风湿性关节炎，组织移植，肿瘤转移和心肌缺血）中的炎性疾病。 化合物也可以用于治疗炎性脑疾病如多发性硬化症。

公开(公告)号：US06492372B1

公开(公告)日：2002-12-10

申请号：US09489377

申请日：2000-01-21

Applicant: Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Susan Ashwell ,  Gregory S. Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren B. Dressen ,  Francine S. Grant ,  Christopher Semko ,  Ying-Zi Xu

Inventor： Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Susan Ashwell ,  Gregory S. Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren B. Dressen ,  Francine S. Grant ,  Christopher Semko ,  Ying-Zi Xu

IPC: A61K3133

CPC classification number: A61K31/425 ,  A61K31/41 ,  A61K31/427 ,  A61K31/433 ,  A61K31/44 ,  A61K31/4439 ,  A61K31/445 ,  A61K31/495 ,  A61K31/496 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/50 ,  A61K31/505 ,  A61K31/506 ,  A61K31/53 ,  A61K31/535 ,  A61K31/54 ,  C07D211/58 ,  C07D213/74 ,  C07D213/76 ,  C07D233/88 ,  C07D239/32 ,  C07D239/42 ,  C07D239/47 ,  C07D239/48 ,  C07D239/52 ,  C07D241/20 ,  C07D249/06 ,  C07D251/18 ,  C07D251/48 ,  C07D251/50 ,  C07D251/52 ,  C07D251/54 ,  C07D257/06 ,  C07D285/06 ,  C07D285/10 ,  C07D333/36 ,  C07D333/48 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/04 ,  C07D413/12 ,  C07D417/12 ,  Y02A50/463 ,  A61K2300/00

Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract translation: 公开了结合VLA-4的化合物。 这些化合物中的某些也抑制白细胞粘附，特别是由VLA-4介导的白细胞粘附。 这样的化合物可用于治疗哺乳动物患者，例如人类例如哮喘，阿尔茨海默氏病，动脉粥样硬化，艾滋病痴呆，糖尿病，炎性肠病，类风湿性关节炎，组织移植，肿瘤转移和心肌缺血等炎性疾病。 化合物也可以用于治疗炎性脑疾病如多发性硬化症。

公开(公告)号：US4320051A

公开(公告)日：1982-03-16

申请号：US179402

申请日：1980-08-19

Applicant: Dimitrios Sarantakis

Inventor： Dimitrios Sarantakis

IPC: C07D295/125 ,  C07D295/185 ,  C07K5/06 ,  C07K5/087 ,  C07C103/52

CPC classification number: C07D295/185 ,  C07D295/125 ,  C07K5/06026 ,  C07K5/0812 ,  Y10S514/809

Abstract: The analgesic tripeptide amides of the formula: ##STR1## in which X.sup.2 is D-Ala, D-Ser, D-Thr, D-Met, D-Cys, D-Trp, or D-Asn;R.sup.1 is hydrogen, alkyl of 1 to 6 carbon atoms, allyl, cyclopropylmethyl or cyclobutylmethyl;R.sup.2 is hydrogen or alkyl of 1 to 6 carbon atoms;R.sup.3 is hydrogen or alkyl of 1 to 6 carbon atoms;R.sup.4 is isobutyl, cyclohexyl, benzyl, p-halobenzyl or p-nitrobenzyl;R.sup.5 is hydrogen or alkyl of 1 to 6 carbon atoms; andR.sup.6 is hydrogen, alkyl of 1 to 6 carbon atoms, 2-hydroxyethyl, benzyl, diphenylmethyl, phenyl, p-halophenyl, p-nitrophenyl, ##STR2## or --CH.sub.2 CH.sub.2 SCH.sub.3 ; or a pharmaceutically acceptable salt thereof.

Abstract translation: 其中X2是D-Ala，D-Ser，D-Thr，D-Met，D-Cys，D-Trp或D-Asn的下式的镇痛三肽酰胺： R1是氢，1-6个碳原子的烷基，烯丙基，环丙基甲基或环丁基甲基; R2是氢或1至6个碳原子的烷基; R3是氢或1至6个碳原子的烷基; R4是异丁基，环己基，苄基，对卤代苄基或对硝基苄基; R5是氢或1至6个碳原子的烷基; R 6为氢，1-6个碳原子的烷基，2-羟基乙基，苄基，二苯基甲基，苯基，对卤代苯基，对硝基苯基，或者-CH 2 CH 2 SCH 3; 或其药学上可接受的盐。

公开(公告)号：US4253997A

公开(公告)日：1981-03-03

申请号：US104599

申请日：1979-12-17

Applicant: Dimitrios Sarantakis

Inventor： Dimitrios Sarantakis

IPC: A61K38/00 ,  C07K7/23 ,  C08L37/00 ,  C07C103/52

CPC classification number: C07K7/23 ,  A61K38/00 ,  Y10S930/13 ,  Y10S930/28

Abstract: The compounds D-p-Glu-D-Phe-D-Nal(1)-L-Ser-L-Tyr-X-L-Leu-L-Arg-L-Pro-Gly-NH.sub.2 where X is D-Nal(1), D-Trp, D-Phe, D-Tyr, D-Lys, D-Met, D-Ala or D-Pgl and pharmaceutically acceptable salts thereof exhibit antiovulatory activity in female mammals and are useful contraceptive agents.

Abstract translation: 化合物Dp-Glu-D-Phe-D-Nal（1）-L-Ser-L-Tyr-XL-Leu-L-Arg-L-Pro-Gly-NH2其中X为D-Nal（1） D-Trp，D-Phe，D-Tyr，D-Lys，D-Met，D-Ala或D-Pgl及其药学上可接受的盐在雌性哺乳动物中表现出抗疟药活性，并且是有用的避孕药。

公开(公告)号：US4178284A

公开(公告)日：1979-12-11

申请号：US968658

申请日：1978-12-11

Applicant: Dimitrios Sarantakis

Inventor： Dimitrios Sarantakis

IPC: A61K38/00 ,  C07K14/665 ,  C07C103/52 ,  A61K37/00

CPC classification number: C07K14/665 ,  A61K38/00 ,  Y10S514/809 ,  Y10S930/28

Abstract: Octapeptide derivatives of Met- and Leu-enkephalin C-terminally modified by addition of L-Lys-Gly-L-Glu-OH or L-Lys-Gly-L-Gln-OH release endogenous growth hormone without analgesia or side effects elicited by the enkephalins or morphine.

Abstract translation: 通过加入L-Lys-Gly-L-Glu-OH或L-Lys-Gly-L-Gln-OH C末端修饰的Met-和Leu-脑啡肽的八肽衍生物释放内源性生长激素而不引起镇痛或副作用 脑啡肽或吗啡。

公开(公告)号：US4081433A

公开(公告)日：1978-03-28

申请号：US759203

申请日：1977-01-13

Applicant: Dimitrios Sarantakis

Inventor： Dimitrios Sarantakis

IPC: A61K38/00 ,  C07K14/655 ,  C07C103/52 ,  A61K37/00

CPC classification number: C07K14/6555 ,  A61K38/00 ,  Y10S514/806 ,  Y10S930/16

Abstract: Polypeptides of the formula: ##STR1## THE LINEAR PRECURSORS, INTERMEDIATES AND NON-TOXIC ACID ADDITION SALTS THEREOF, WHEREINR is hydrogen or Ala--Gly;X.sub.4 is D--Nle, D--Val, D--Phe, D--Tyr or D--Trp; andX.sub.8 is L--Trp or D--TrpAre described. These polypeptides inhibit the secretion of growth hormone.

Abstract translation: 下式的多肽：线性前体，中间体和非毒性添加剂，其中R为氢或Ala-Gly; X4是D-Nle，D-Val，D-Phe，D-Tyr或D-Trp; X8是L-Trp或D-Trp描述的。 这些多肽抑制生长激素的分泌。