- Kilogram synthesis of a second-generation LFA-1/ICAM inhibitor
-
The process development and the kilogram-scale synthesis of BMS-688521 (1) are described. The synthesis features a highly efficient telescoped sequence which utilizes previously described spirocyclic hydantoin (4b) to produce the final intermediate via an
- Delmonte, Albert J.,Fan, Yu.,Girard, Kevin P.,Jones, Gregory S.,Waltermire, Robert E.,Rosso, Victor,Wang, Xuebao
-
-
Read Online
- PHD INHIBITOR COMPOUNDS, COMPOSITIONS, AND THEIR USE
-
The present invention provides, in part, novel small molecule inhibitors of PHD, having a structure according to Formula (A), and sub-formulas thereof: or a pharmaceutically acceptable salt thereof. The compounds provided herein can be useful for treatmen
- -
-
Paragraph 0338-0339
(2021/09/26)
-
- PHD INHIBITOR COMPOUNDS, COMPOSITIONS, AND USE
-
The present invention provides, in part, novel small molecule inhibitors of PHD, having a structure according to Formula (A), and sub-formulas thereof: or a pharmaceutically acceptable salt thereof. The compounds provided herein can be useful for treatment of diseases including heart ( e.g. ischemic heart disease, congestive heart failure, and valvular heart disease), lung (e.g., acute lung injury, pulmonary hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease), liver (e.g. acute liver failure and liver fibrosis and cirrhosis), and kidney (e.g. acute kidney injury and chronic kidney disease) disease.
- -
-
Paragraph 0407-0408
(2021/09/26)
-
- PHD INHIBITOR COMPOUNDS, COMPOSITIONS, AND USE
-
The present invention provides, in part, novel small molecule inhibitors of PHD, having a structure according to Formula (A), and sub-formulas thereof, or a pharmaceutically acceptable salt thereof. The compounds provided herein can be useful for treatmen
- -
-
Paragraph 0339-0340; 0369-0370; 0563-0564
(2021/09/26)
-
- Synthetic method for 1-(ethoxycarbonyl)imidazo[1,5]pyridine-6-carboxylic acid
-
The invention relates to a synthetic method for 1-(ethoxycarbonyl)imidazo[1,5]pyridine-6-carboxylic acid, and mainly solves the technical problem that a current method is not suitable for industrial synthesis. The method comprises the following three steps: step 1, firstly performing a reaction on a compound 1 and di-tert-butyl dicarbonate in solvent tetrahydrofuran under the action of 4-dimethylaminopyridine to obtain a compound 2; step2, performing a reaction on the compound 2 and ethyl cyanoacetate in solvent N,N-dimethylformamide under the action of cesium carbonate to obtain a compound 3;and step 3, performing a reaction on the compound 3 under the action of hydrochloric acid-ethyl acetate to obtain the 1-(ethoxycarbonyl)imidazo[1,5]pyridine-6-carboxylic acid. The reaction formula isshown in the description.
- -
-
Paragraph 0007
(2019/10/01)
-
- CEREBLON LIGANDS AND BIFUNCTIONAL COMPOUNDS COMPRISING THE SAME
-
The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.
- -
-
Paragraph 0897; 0909; 0910; 0911; 0912; 0913; 0914
(2018/08/20)
-
- Discovery of novel series of 6-benzyl substituted 4-aminocarbonyl-1,4- diazepane-2,5-diones as human chymase inhibitors using structure-based drug design
-
A novel series of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5- diones were explored as human chymase inhibitors using structure-based drug design according to the X-ray cocrystal structure of chymase and compound 1. The optimization focused on
- Tanaka, Taisaku,Sugawara, Hajime,Maruoka, Hiroshi,Imajo, Seiichi,Muto, Tsuyoshi
-
p. 4233 - 4249
(2013/07/27)
-
- Preparation of 2-, 4-, 5-, and 6-aminonicotinic acid tert-butyl esters
-
Procedures are reported to prepare the tert-butyl esters of 2-aminonicotinic acid, 4-aminonicotinic acid, 5-aminonicotinic acid, and 6-aminonicotinic acid from 2-chloronicotinic acid, 4-chloronicotinic acid, 5-bromonicotinic acid, and 6-chloronicotinic acid, respectively, without need for purification of intermediates. Copyright
- Wright, Stephen W.
-
experimental part
p. 442 - 445
(2012/06/15)
-
- DERIVATIVES OF 2-PYRIDIN-2-YL-PYRAZOL-3(2H)-ONE, PREPARATION AND THERAPEUTIC USE THEREOF
-
The invention relates to compounds corresponding to formula (I), in the form of the base or of an acid-addition salt: in which n is equal to 0, 1, 2, 3 or 4; m is equal to 0, 1 or 2; o is equal to 0 or 1; X represents a group —CH2, —CH(R′)—, —N
- -
-
Page/Page column 12
(2011/12/14)
-
- A new and efficient synthesis of 6-[(5 S,9 R)-9-(4-Cyanophenyl)-3-(3,5- dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl]nicotinic acid, a potent LFA-1/ICAM inhibitor
-
An efficient synthesis of 6-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5- dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl]nicotinic acid 1 is described. This new process involves an in situ protection of 6-chloronicotinic acid as trimethylsilyl est
- Zhang, Huiping,Watterson, Scott H.,Xiao, Zili,Dhar, T. G. Murali,Balasubramanian, Balu,Barrish, Joel C.,Chen, Bang-Chi
-
scheme or table
p. 936 - 938
(2011/03/20)
-
- Small molecule antagonist of leukocyte function associated antigen-1 (LFA-1): Structure-activity relationships leading to the identification of 6-((5 S,9 R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7- triazaspiro[4.4]nonan-7-yl)nico
-
Leukocyte function-associated antigen-1 (LFA-1), also known as CD11a/CD18 or αLβ2, belongs to the β2 integrin subfamily and is constitutively expressed on all leukocytes. The major ligands of LFA-1 include three intercellu
- Watterson, Scott H.,Xiao, Zili,Dodd, Dharmpal S.,Tortolani, David R.,Vaccaro, Wayne,Potin, Dominique,Launay, Michele,Stetsko, Dawn K.,Skala, Stacey,Davis, Patric M.,Lee, Deborah,Yang, Xiaoxia,McIntyre, Kim W.,Balimane, Praveen,Patel, Karishma,Yang, Zheng,Marathe, Punit,Kadiyala, Pathanjali,Tebben, Andrew J.,Sheriff, Steven,Chang, Chiehying Y.,Ziemba, Theresa,Zhang, Huiping,Chen, Bang-Chi,Delmonte, Albert J.,Aranibar, Nelly,McKinnon, Murray,Barrish, Joel C.,Suchard, Suzanne J.,Murali Dhar
-
experimental part
p. 3814 - 3830
(2010/07/05)
-
- CRYSTALLINE FORMS OF6- [(5S, 9R) -9- (4-CYANOPHENYL) -3-(3, 5-DICHLOROPHENYL) -1-METHYL-2, 4-DIOXO-1, 3, 7-TRIAZASPIRO [4.4] NON-7-YL] NICOTINIC
-
The invention provides crystalline forms of 6-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl]nicotinic acid, its pharmaceutically acceptable salts, or solvates, thereof Further, a process is provided fo
- -
-
Page/Page column 67; 68
(2010/11/08)
-
- Efficient synthesis of novel NK1 receptor antagonists: Selective 1,4-addition of Grignard reagents to 6-chloronicotinic acid derivatives
-
A new efficient synthesis of two novel classes of NK1 receptor antagonists, among them befetupitant and netupitant, starting from 6-chloronicotinic acid is described. The introduction of the o-tolyl substituent at C(4) of the pyridine ring was achieved by a one-pot selective 1,4-Grignard addition/oxidation sequence to 6-chloronicotinic acid or a derivative of it. The scope of this addition/oxidation sequence was examined. It was also shown that the carboxylic function can be converted to a methyl amino group by a Hofmann rearrangement followed by reduction. Furthermore, a new high-yielding synthesis of 2-(3,5-bistrifluoromethylphenyl)-2-methyl propionic acid based on the carbonylation of the tertiary alcohol obtained by Grignard addition of 3,5-bis(trifluoromethyl)bromobenzene to acetone was established.
- Hoffmann-Emery, Fabienne,Hilpert, Hans,Scalone, Michelangelo,Waldmeier, Pius
-
p. 2000 - 2008
(2007/10/03)
-
- Oxazolidinone combinatorial libraries, compositions and methods of preparation
-
Oxazolidinones and methods for their synthesis are provided. Also provided are combinatorial libraries comprising oxazolidinones, and methods to prepare the libraries. Further provided are methods of making biologically active oxazolidinones as well as pharmaceutically acceptable compositions comprising the oxazolidinones. The methods of library preparation include the attachment of oxazolidinones to a solid support. The methods of compound preparation in one embodiment involve the reaction of an iminophosphorane with a carbonyl containing polymeric support.
- -
-
-
