NBI 30545 | 195054-99-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: NBI 30545
• 英文别名: 3-(2,4-dimethoxyphenyl)-2,5-dimethyl-7-(N-propyl-N-methyloxyethylamino)-pyrazolo [2,3-a]pyrimidine；Pyrazolo(1,5-a)pyrimidin-7-amine, 3-(2,4-dimethoxyphenyl)-N-(2-methoxyethyl)-2,5-dimethyl-N-propyl-；3-(2,4-dimethoxyphenyl)-N-(2-methoxyethyl)-2,5-dimethyl-N-propylpyrazolo[1,5-a]pyrimidin-7-amine
• CAS: 195054-99-0
• 化学式: C₂₂H₃₀N₄O₃
• 分子量: 398.505
• InChiKey: AKFWXFDMKRSYRD-UHFFFAOYSA-N

物化性质

• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  61.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-(2,4-二甲氧基苯基)乙腈 在 盐酸肼 、 sodium hydride 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 生成 NBI 30545
  参考文献：
  名称：

  Optimization of 3-phenylpyrazolo[1,5- a ]pyrimidines as potent corticotropin-releasing factor-1 antagonists with adequate lipophilicity and water solubility

  摘要：

  In our efforts to identify potent CRF1 antagonists with proper physicochemical properties, a series of 3-phenylpyrazolo[1,5-a]pyrimidines bearing polar groups, such as amino, hydroxyl, methoxy, sulfoxide, were designed and synthesized. Several positions of the core structure were identified, where a polar group was tolerated with slight reduction in receptor binding. NBI 30545 (18n) was found to have good binding affinity and potent antagonistic activity at the human CRF1 receptor. Moreover, this compound had proper lipophilicity (log D = 2.78) and good solubility in water (>10 mg/mL), and exhibited good plasma and brain exposure when given orally. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.019

文献信息

• PYRAZOLOPYRIMIDINES AS CRF RECEPTOR ANTAGONISTS
  申请人：——

  公开号：US20030125341A1

  公开（公告）日：2003-07-03

  This invention concerns compounds of formula 1 including the stereoisomers and the pharmaceutically acceptable acid addition salt forms thereof, wherein R 1 is NR 4 R 5 or OR 5 ; R 2 is C 1-6 alkyl, C 1-6 alkyloxy or C 1-6 alkylthio; R 3 is hydrogen, C 1-6 alkyl, C 1-6 alkylsulfonyl, C 1-6 alkylsulfoxy or C 1-6 alkylthio; R 4 is hydrogen, C 1-6 alkyl, mono- or di(C 3-6 cycloalkyl)methyl, C 3-6 cycloalkyl, C 3-6 alkenyl, hydroxyC 1-6 alkyl, C 1-6 alkylcarbonyloxyC 1-6 alkyl or C 1-6 alkyloxyC 1-6 alkyl; R 5 is C 1-8 alkyl, mono- or di(C 3-6 cycloalkyl)methyl, Ar 1 CH 2 , C 1-6 alkyloxyC 1-6 alkyl, hydroxyC 1-6 alkyl, C 3-6 alkenyl, thienylmethyl, furanylmethyl, C 1-6 alkylthioC 1-6 alkyl, morpholinyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl, di(C 1-6 alkyl)amino, C 1-6 alkylcarbonylC 1-6 alkyl, C 1-6 alkyl substituted with imidazolyl; or a radical of formula —Alk-O—CO—Ar 1 ; or R 4 and R 5 taken together with the nitrogen atom to which they are attached may form an optionally substituted pyrrolidinyl, piperidinyl, homopiperidinyl or morpholinyl group; having CRF receptor antagonistic properties; pharmaceutical compositions containing such compounds as active ingredients; methods of treating disorders related to hypersecretion of CRF such as depression, anxiety, substance abuse, by administering an effective amount of a compound of formula (I).

  本发明涉及公式1的化合物，包括其立体异构体和药学上可接受的酸加成盐形式，其中R1是NR4R5或OR5；R2是C1-6烷基，C1-6烷氧基或C1-6烷硫基；R3是氢，C1-6烷基，C1-6烷基磺酰基，C1-6烷基磺酸氧基或C1-6烷基硫基；R4是氢，C1-6烷基，单或双（C3-6环烷基）甲基，C3-6环烷基，C3-6烯基，羟基C1-6烷基，C1-6烷基羰酸酯氧基C1-6烷基或C1-6烷氧基C1-6烷基；R5是C1-8烷基，单或双（C3-6环烷基）甲基，Ar1CH2，C1-6烷氧基C1-6烷基，羟基C1-6烷基，C3-6烯基，噻吩甲基，呋喃甲基，C1-6烷硫基C1-6烷基，吗啉基，单或双（C1-6烷基）氨基C1-6烷基，双（C1-6烷基）氨基，C1-6烷基羰基C1-6烷基，C1-6烷基取代的咪唑基；或公式—Alk-O—CO—Ar1的基团；或R4和R5与它们连接的氮原子一起可以形成可选取代的吡咯烷基，哌啶基，同源哌啶基或吗啉基；具有CRF受体拮抗性质；含有此类化合物作为活性成分的药物组合物；通过给予公式（I）的化合物的有效量治疗与CRF过度分泌相关的紊乱，如抑郁症，焦虑症，物质滥用等的方法。
• [EN] PYRAZOLOPYRIMIDINES AS CRF RECEPTOR ANTAGONISTS<br/>[FR] PYRAZOLOPYRIMIDINES EN TANT QU'ANTAGONISTES DU RECEPTEUR DE CRF
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1997029109A1

  公开（公告）日：1997-08-14

  (EN) This invention concerns compounds of formula (I), including the stereoisomers and the pharmaceutically acceptable acid addition salt forms thereof, wherein R1 is NR4R5 or OR5; R2 is C1-6alkyl, C1-6alkyloxy or C1-6alkylthio; R3 is hydrogen, C1-6alkyl, C1-6alkylsulfonyl, C1-6alkylsulfoxy or C1-6alkylthio; R4 is hydrogen, C1-6alkyl, mono- or di(C3-6cycloalkyl)methyl, C3-6cycloalkyl, C3-6alkenyl, hydroxyC1-6alkyl, C1-6alkylcarbonyloxyC1-6alkyl or C1-6alkyloxyC1-6alkyl; R5 is C1-8alkyl, mono- or di(C3-6cycloalkyl)methyl, Ar1CH2, C1-6alkyloxyC1-6alkyl, hydroxyC1-6alkyl, C3-6alkenyl, thienylmethyl, furanylmethyl, C1-6alkylthioC1-6alkyl, morpholinyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, di(C1-6alkyl)amino, C1-6alkylcarbonylC1-6alkyl, C1-6alkyl substituted with imidazolyl; or a radical of the formula -Alk-O-CO-Ar1; or R4 and R5 taken together with the nitrogen atom to which they are attached may form an optionally substituted pyrrolidinyl, piperidinyl, homopiperidinyl or morpholinyl group; having CRF receptor antagonistic properties; pharmaceutical compositions containing such compounds as active ingredients; methods of treating disorders related to hypersecretion of CRF such as depression, anxiety, substance abuse, by administering an effective amount of a compound of formula (I).(FR) L'invention concerne des composés représentés par la formule (I) comprenant les stéréo-isomères, ainsi que leurs sels d'addition d'acide acceptables sur le plan pharmaceutique, dans laquelle R1 représente NR4R5 ou OR5; R2 représente alkyle C1-6, alkyloxy C1-6 ou alkylthio C1-6; R3 représente hydrogène, alkyle C1-6, alkylsulfonyle C1-6, alkylsulfoxy C1-6 ou alkylthio C1-6; R4 représente hydrogène, alkyle C1-6, mono- ou di(C3-6 cycloalkyle)méthyle, cycloalkyle C3-6, alkényle C3-6, hydroxyalkyle C1-6, alkylcarbonyloxy C1-6 alkyle C1-6 ou alkyloxy C1-6 alkyle C1-6; R5 représente alkyle C1-8, mono- ou di(cycloalkyle C3-6)méthyle, Ar1CH2, alkyloxy C1-6 alkyle C1-6, hydroxyalkyle C1-6, alkényle C3-6, thienylméthyle, furanylméthyle, alkylthio C1-6 alkyle C1-6, morpholinyle, mono- ou di(alkyle C1-6)aminoalkyle C1-6, di(alkyle C1-6)amino, alkylcarbonyle C1-6 alkyle C1-6; alkyle C1-6 substitué par imidazolyle; ou un radical représenté par la formule -Alk-O-CO-Ar1; ou R4 et R5, pris ensemble avec l'atome d'azote auquel ils sont fixés, peuvent constituer un groupe éventuellement substitué pyrrolidinyle, pipéridinyle, homopipéridinyle ou morpholinyle; possédant des propriétés d'antagonistes du récepteur de CRF; des compositions pharmaceutiques contenant ces composés en tant qu'ingrédients actifs; des procédés servant à traiter des maladies provoquées par l'hypersécrétion de CRF, telles que la dépression, l'anxiété, la toxicomanie, au moyen de l'administration d'une quantité efficace d'un composé représenté par la formule (I).

  该发明涉及式(I)的化合物，包括其立体异构体和药学上可接受的酸加成盐形式，其中R1为NR4R5或OR5；R2为C1-6烷基，C1-6烷氧基或C1-6烷硫基；R3为氢，C1-6烷基，C1-6烷基磺酰基，C1-6烷基亚磺酸基或C1-6烷基硫基；R4为氢，C1-6烷基，单或双(C3-6环烷基)甲基，C3-6环烷基，C3-6烯基，羟基C1-6烷基，C1-6烷基羧酸酯氧基C1-6烷基或C1-6烷氧基C1-6烷基；R5为C1-8烷基，单或双(C3-6环烷基)甲基，Ar1CH2，C1-6烷氧基C1-6烷基，羟基C1-6烷基，C3-6烯基，噻吩基甲基，呋喃基甲基，C1-6烷硫基C1-6烷基，吗啡啉基，单或双(C1-6烷基)氨基C1-6烷基，双(C1-6烷基)氨基，C1-6烷基羧酰基C1-6烷基，C1-6烷基取代咪唑基；或式-Alk-O-CO-Ar1的基团；或R4和R5与它们连接的氮原子一起可以形成一个可选的取代的吡咯烷基，哌啶基，同型哌啶基或吗啡啉基；具有CRF受体拮抗作用；含有这种化合物作为活性成分的制药组合物；通过给予式(I)化合物的有效量来治疗与CRF过度分泌有关的疾病，例如抑郁症、焦虑症、物质滥用的方法。
• Pyrazolopyrimidines as CRF receptor antagonists
  申请人：Neurocrine Biosciences, Inc.

  公开号：US20040127483A1

  公开（公告）日：2004-07-01

  This invention concerns compounds of formula 1 including the stereoisomers and the pharmaceutically acceptable acid addition salt forms thereof, wherein R 1 is NR 4 R 5 or OR 5 ; R 2 is C 1-6 alkyl, C 1-6 alkyloxy or C 1-6 alkylthio; R 3 is hydrogen, C 1-6 alkyl, C 1-6 alkylsulfonyl, C 1-6 alkylsulfoxy or C 1-6 alkylthio; R 4 is hydrogen, C 1-6 alkyl, mono- or di(C 3-6 cycloalkyl)methyl, C 3-6 cycloalkyl, C 3-6 alkenyl, hydroxyC 1-6 alkyl, C 1-6 alkylcarbonyloxyC 1-6 alkyl or C 1-6 alkyloxyC 1-6 alkyl; R 5 is C 1-8 alkyl, mono- or di(C 3-6 cycloalkyl)methyl, A 1 CH 2 , C 1-6 alkyloxyC 1-6 alkyl, hydroxyC 1-6 alkyl, C 3-6 alkenyl, thienylmethyl, furanylmethyl, C 1-6 alkylthioC 1-6 alkyl, morpholinyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl, di(C 1-6 alkyl)amino, C 1-6 alkylcarbonylC 1-6 alkyl, C 1-6 alkyl substituted with imidazolyl; or a radical of formula —Alk—O—CO—Ar 1 ; or R 4 and R 5 taken together with the nitrogen atom to which they are attached may form an optionally substituted pyrrolidinyl, piperidinyl, homopiperidinyl or morpholinyl group; having CRF receptor antagonistic properties; pharmaceutical compositions containing such compounds as active ingredients; methods of treating disorders related to hypersecretion of CRF such as depression, anxiety, substance abuse, by administering an effective amount of a compound of formula (I).

  本发明涉及式1的化合物，包括其立体异构体和药物可接受的酸盐形式，其中R1是NR4R5或OR5; R2是C1-6烷基，C1-6烷氧基或C1-6烷硫基; R3是氢，C1-6烷基，C1-6烷基磺酰基，C1-6烷基磺酸氧基或C1-6烷基硫基; R4是氢，C1-6烷基，单或双（C3-6环烷基）甲基，C3-6环烷基，C3-6烯基，羟基C1-6烷基，C1-6烷基羰酰氧基C1-6烷基或C1-6烷氧基C1-6烷基; R5是C1-8烷基，单或双（C3-6环烷基）甲基，A1CH2，C1-6烷氧基C1-6烷基，羟基C1-6烷基，C3-6烯基，噻吩基甲基，呋喃基甲基，C1-6烷硫基C1-6烷基，吗啉基，单或双（C1-6烷基）氨基C1-6烷基，二（C1-6烷基）氨基，C1-6烷基羰基C1-6烷基，C1-6烷基取代咪唑基; 或式—Alk—O—CO—Ar1的基团; 或R4和R5与它们连接的氮原子一起可以形成可选取代的吡咯烷基，哌啶基，同型哌啶基或吗啡基; 具有CRF受体拮抗性质; 包含此类化合物作为活性成分的制药组合物; 通过给予式（I）化合物的有效量来治疗与CRF高分泌相关的疾病，例如抑郁症，焦虑症，物质滥用等的方法。
• Use of corticotropin releasing factor antagonists for treating syndrome X
  申请人：Pfizer Products Inc.

  公开号：EP1097709A2

  公开（公告）日：2001-05-09

  The present invention relates to compositions and methods of achieving a thereapeutic effect including, the treatment or prevention of syndrome X in an animal, preferably a mammal including a human subject or a companion animal, using a corticotropin releasing factor (CRF) antagonist alone or together with a glucocorticoid receptor antagonist.

  本发明涉及单独使用促肾上腺皮质激素释放因子（CRF）拮抗剂或与糖皮质激素受体拮抗剂一起使用以达到治疗或预防动物（最好是哺乳动物，包括人类或伴侣动物）X综合征的效果的组合物和方法。
• Combinations of corticotropin releasing factor antagonists and growth hormone secretagogues
  申请人：Pfizer Products Inc.

  公开号：EP1149583A2

  公开（公告）日：2001-10-31

  This invention is directed to pharmaceutical compositions comprising corticotropin releasing factor antagonist and growth hormone or growth hormone secretagogues, prodrugs thereof, or pharmaceutically acceptable salts of said compounds or said prodrugs. The invention is also directed to the use of such compositions in the treatment or prevention of osteoporosis and heart-related diseases (including congestive heart failure) in mammals, particularly humans.

  本发明涉及包含促肾上腺皮质激素释放因子拮抗剂和生长激素或生长激素促泌剂、其原药或所述化合物或所述原药的药学上可接受的盐的药物组合物。本发明还用于治疗或预防哺乳动物，特别是人类的骨质疏松症和心脏相关疾病（包括充血性心力衰竭）。