N'-[4-(2-Methyl-2H-tetrazol-5-yl)-benzyl]-hydrazinecarboxylic acid tert-butyl ester | 198904-72-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N'-[4-(2-Methyl-2H-tetrazol-5-yl)-benzyl]-hydrazinecarboxylic acid tert-butyl ester
• 英文别名: tert-butyl N-[[4-(2-methyltetrazol-5-yl)phenyl]methylamino]carbamate
• CAS: 198904-72-2
• 化学式: C₁₄H₂₀N₆O₂
• 分子量: 304.352
• InChiKey: XUNCJJLFEOGOQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  94
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N'-[4-(2-Methyl-2H-tetrazol-5-yl)-benzyl]-hydrazinecarboxylic acid tert-butyl ester 在 盐酸 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 24.0h， 生成 (2S,3S)-3-Amino-1-{N-[4-(2-methyl-2H-tetrazol-5-yl)-benzyl]-hydrazino}-4-phenyl-butan-2-ol; hydrochloride
  参考文献：
  名称：

  New Aza-Dipeptide Analogues as Potent and Orally Absorbed HIV-1 Protease Inhibitors:  Candidates for Clinical Development

  摘要：

  On the basis of previously described X-ray studies of an enzyme/aza-dipeptide complex,(8) azadipeptide analogues carrying N-(bis-aryl-methyl) substituents on the (hydroxethyl)hydrazine moiety have been designed and synthesized as HIV-1 protease inhibitors. By using either equally (12) ororthogonally (13) protected dipeptide isosteres, symmetrically and asymmetrically acylated aza-dipeptides can be synthesized. This approach led to the discovery of very potent inhibitors with antiviral activities (ED50) in the subnanomolar range. Acylation of the (hydroxethyl)hydrazine dipeptide isostere with the L-tert-leucine derivative 29 increased the oral bioavailability significantly when compared to the corresponding L-valine or L-isoleucine derivatives. The bis(L-tert-leucine) derivatives CGP 75355, CGP 73547, CGP 75136, and CGP 75176 combine excellent antiviral activity with high blood concentration after oral administration. Furthermore, they show no cross-resistance with saquinavir-resistant strains and maintain activity against indinavir-resistant ones. Consequently they qualify for further profiling as potential clinical candidates.

  DOI：

  10.1021/jm970873c
• 作为产物：
  描述：

  4-(2-methyl-2H-tetrazol-5-yl)-benzaldehyde 在 potassium tetraborate 、 sodium cyanoborohydride 、 对甲苯磺酸 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 N'-[4-(2-Methyl-2H-tetrazol-5-yl)-benzyl]-hydrazinecarboxylic acid tert-butyl ester
  参考文献：
  名称：

  New Aza-Dipeptide Analogues as Potent and Orally Absorbed HIV-1 Protease Inhibitors:  Candidates for Clinical Development

  摘要：

  On the basis of previously described X-ray studies of an enzyme/aza-dipeptide complex,(8) azadipeptide analogues carrying N-(bis-aryl-methyl) substituents on the (hydroxethyl)hydrazine moiety have been designed and synthesized as HIV-1 protease inhibitors. By using either equally (12) ororthogonally (13) protected dipeptide isosteres, symmetrically and asymmetrically acylated aza-dipeptides can be synthesized. This approach led to the discovery of very potent inhibitors with antiviral activities (ED50) in the subnanomolar range. Acylation of the (hydroxethyl)hydrazine dipeptide isostere with the L-tert-leucine derivative 29 increased the oral bioavailability significantly when compared to the corresponding L-valine or L-isoleucine derivatives. The bis(L-tert-leucine) derivatives CGP 75355, CGP 73547, CGP 75136, and CGP 75176 combine excellent antiviral activity with high blood concentration after oral administration. Furthermore, they show no cross-resistance with saquinavir-resistant strains and maintain activity against indinavir-resistant ones. Consequently they qualify for further profiling as potential clinical candidates.

  DOI：

  10.1021/jm970873c

文献信息

• [EN] ANTIVIRALLY ACTIVE HETEROCYCLIC AZAHEXANE DERIVATIVES<br/>[FR] DERIVES D'AZAHEXANE HETEROCYCLIQUES A ACTIVITE ANTIVIRALE
  申请人：NOVARTIS AG

  公开号：WO1997040029A1

  公开（公告）日：1997-10-30

  (EN) There are described compounds of formula (I*) wherein R1 is lower alkoxycarbonyl, R2 is secondary or tertiary lower alkyl or lower alkylthio-lower alkyl, R3 is phenyl that is unsubsituted or substituted by one or more lower alkoxy radicals, or C4-C8cycloalkyl, R4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl (-SO-) and sulfonyl (-SO2-) and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl, R5, independently of R2, has one of the meanings mentioned for R2, and R6, independently of R1, is lower alkoxycarbonyl, or salts thereof, provided that at least one salt-forming group is present. The compounds are inhibitors of retroviral aspartate protease and can be used, for example, in the treatment of AIDS. They exhibit outstanding pharmacodynamic properties.(FR) L'invention se rapporte à des composés de la formule (I*) dans laquelle R1 représente alcoxycarbonyle inférieur, R2 représente un alkyle inférieur secondaire ou tertiaire ou un alkylthio inférieur-alkyl inférieur, R3 représente phényle qui est substitué ou non par un ou plusieurs radicaux alcoxy inférieur, ou cycloalkyle en C4-C8, R4 représente phényle ou cyclohéxyle, chacun substitué en position 4 par un hétérocyclyle insaturé qui est lié par un atome de carbone du cycle, possède de 5 à 8 atomes cycliques, renferme de 1 à 4 hétéroatomes sélectionnés parmi azote, oxygène, soufre, sulfinyle (-SO-) et sulfonyle (-SO2-) et à substituer ou non par alkyle inférieur ou par phényl-alkyle inférieur, R5, indépendamment de R2, possède l'une des significations précitées pour R2, et R6, indépendamment de R1, représente alcoxycarbonyle inférieur, ou à des sels de ces composés, à condition qu'au moins un groupe formant un sel soit présent. Ces composés sont des inhibiteurs de l'aspartate protéase rétrovirale et peuvent être utilisés, par exemple, dans le traitement du SIDA. Ils présentent d'excellentes propriétés pharmacodynamiques.

  (中文) 描述了式(I*)的化合物，其中R1为低级烷氧羰基，R2为次级或三级低级烷基或低级烷硫基-低级烷基，R3为苯基，未取代或被一个或多个低级烷氧基取代，或C4-C8环烷基，R4为苯基或环己基，每个取代在4位上的不饱和杂环基通过一个环碳原子相连，具有5-8个环原子，包含1-4个从氮、氧、硫、亚硫基(-SO-)和磺酰基(-SO2-)中选取的杂原子，未取代或被低级烷基或苯基-低级烷基取代，R5与R2独立，具有R2中提到的其中一种含义，R6与R1独立，为低级烷氧羰基或其盐，前提是至少存在一个形成盐的基团。这些化合物是逆转录病毒天冬氨酸蛋白酶抑制剂，可以用于治疗艾滋病等疾病。它们具有出色的药理学特性。
• ANTIVIRALLY ACTIVE HETEROCYCLIC AZAHEXANE DERIVATIVES
  申请人：Novartis AG

  公开号：EP0900210B1

  公开（公告）日：2005-02-09
• US5849911A
  申请人：——

  公开号：US5849911A

  公开（公告）日：1998-12-15
• US6110946A
  申请人：——

  公开号：US6110946A

  公开（公告）日：2000-08-29
• US6166004A
  申请人：——

  公开号：US6166004A

  公开（公告）日：2000-12-26