- Crystal form of quinoline TGF-beta1 inhibitor
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The invention belongs to the field of medical chemistry, and relates to a crystal form of a quinoline TGF-beta1 inhibitor as well as a preparation method and application of the crystal form, in particular to a crystal form of 4-((1-cyclopropyl-3-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl) oxy)-7-(3-(trifluoromethyl)-5, 6-dihydro-[1, 2, 4] triazolo [4, 3-a] pyrazine-7 (8H)-yl) quinoline as shown in a formula (I) and a preparation method of the crystal form. The crystal form can be used for preparing medicines for treating and/or preventing cancers, tissue hyperplasia diseases, fibrosis or inflammatory diseases.
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Paragraph 0073; 0102-0104
(2021/10/27)
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- Medicinal salt of quinoline TGF-beta1 inhibitor and preparation method thereof
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The invention belongs to the field of medical chemistry, and relates to a medicinal salt of a quinoline TGF-beta1 inhibitor, or a hydrate, a solvate or a crystal thereof, and a preparation method and application thereof. Specifically, the invention relates to a medicinal salt of 4-((1-cyclopropyl-3-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl) oxy)-7-(3-(trifluoromethyl)-5, 6-dihydro-[1, 2, 4] triazolo [4, 3-a] pyrazine-7 (8H)-yl) quinoline as shown in a formula (I), or a hydrate, a solvate or a crystal thereof, and a preparation method thereof. The medicinal salt or the hydrate, the solvate or the crystal thereof can be used for preparing medicines for treating and/or preventing cancers, tissue hyperplasia diseases, fibrosis or inflammatory diseases.
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Paragraph 0044; 0073-0075
(2021/10/27)
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- Method for preparing quinoline TGF-β1 inhibitor
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The invention belongs to the field of pharmaceutical chemistry, and relates to a preparation method of quinoline TGF-β1 inhibitor, in particular to I ((4 -) propyl 1 - (tetrahydro -3 - pyran - 2H - yl) -4 - pyrazole - 1H -yloxy) -4 - (-7 - (trifluoromethyl) 3 -5 dihydro 6 - [- 1] triazolo [2, 4] pyrazine 4 (8H) 3 - a -7-yl) quinoline or a salt thereof. A process for the preparation of a hydrate, solvate or crystal.
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Paragraph 0052; 0070; 0099-0101
(2021/10/27)
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- Quinoline compound Preparation method and application thereof
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The invention belongs to the field of pharmaceutical chemistry, and particularly relates to a quinoline compound, a preparation method thereof and application thereof as reference control product in 4 - ((1 - cyclopropyl -3 - (tetrahydro - 2H - pyran -4 - yl) - 1H - pyrazole -4 -yloxy) -7 - (3 -trifluoromethyl) -5, 6 - dihydro - [1, 2] pyrazino [4, 4] pyrazine 3 - a (8H) -7 -yl) quinoline bulk drug.
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Paragraph 0047; 0076-0078
(2021/10/27)
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- Sitagliptin synthesis method
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The invention discloses a sitagliptin synthesis method, which comprises: carrying out a reaction on a compound represented by a formula IV, (R)-(+)-tert-butyl sulfinamide and hydrogen under the catalysis of a catalyst to obtain a compound represented by a formula V; and carrying out a hydrolysis reaction on the compound represented by the formula V to obtain a compound represented by a formula VI,ie., sitagliptin. According to the present invention, the method has advantages of easily available raw materials, simple steps, high yield and mild reaction conditions, and is suitable for industrial production. The formulas IV, V and VI are defined in the specification.
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Paragraph 0032; 0036; 0037; 0052-0060
(2018/07/07)
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- Methods for Treating Cognitive Disorders Using Inhibitors of Histone Deacetylase
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This disclosure relates to compounds for the inhibition of histone deacetylase and treatment of a cognitive disorder or deficit. More particularly, the disclosure provides for compounds of formula (I) wherein Q, J, L and Z are as defined in the specification.
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- Mannich base derivatives of 1,2,4-triazocyclo [4,3-alpha] condensed piperazine as well as preparation method and application of Mannich base derivatives
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Mannich base derivatives of 1,2,4-triazocyclo [4,3-alpha] condensed piperazine have the structural formula shown as general formula I in the specification. The Mannich base derivatives have the following advantages: according to a preparation method, substitutive derivatives are prepared from 1,2,4-triazocyclo [4,3-alpha] condensed piperazine by introducing different substituent groups into 1,2,4-triazocyclo [4,3-alpha] condensed piperazine, a novel structure with higher biological activity is discovered, novel structure-activity relationship and biological activity laws are summarized; the prepared Mannich base derivatives have higher bactericidal activity and herbicidal activity, have high in-vitro inhibitory activity for plant pathogens such as fusarium wilt pathogen of cucumbers, cercospora arachidicola, Macrophoma kawatsukai, rhizoctonia cerealis pathogen, alternaria solani of tomatoes, gibberella zeae and the like and can be used for controlling fungus and weed damage to plants, and bactericidal or herbicidal composition further comprises a vector acceptable in agriculture, forestry and hygiene.
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Paragraph 0037; 0038; 0039
(2017/08/02)
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- BETA-AMINO HETEROCYCLIC DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to compounds which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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Paragraph 0209
(2015/12/30)
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- AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
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The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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Paragraph 0283-0284
(2014/08/19)
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- Exploring the unexplored practical and alternative synthesis of 3-(trifluoromethyl)-triazolopiperazine the key intermediate for Sitagliptin
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The practical synthesis of 3-(trifluoromethyl)-triazolopiperazine the key intermediate of Sitagliptin and 3-(trifluoromethyl)-triazolopyridine was carried out employing industrially feasible transformations. The other advantage of this method is the new environment friendly approach to synthesize triazolopiperazine and triazolopyridines by eliminating the commonly used trifluoroacetic anhydride and polyphosphoric acid.
- Nitlikar, Lakshmikant H.,Darandale, Sunil N.,Shinde, Devanand B.
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p. 348 - 352
(2013/07/26)
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- AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
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The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter-and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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Paragraph 00200
(2013/06/05)
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- Synthesis of 3,3-dimethylglutamic acid derivatives as DPP-IV inhibitors and evaluation of their chemical stability
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A novel five-step synthesis of Boc-3,3-dimethylglutamic acid α-ethyl ester 11 is reported. All the steps are high yielding and simple to carry out. By use of the 3,3-dimethylglutamic acid building block, we successfully discovered a novel class of DPP-IV inhibitors, Glu-Pro-Nitrile dipeptide mimics 2, with high potency (IC50 40 nM). The consequence of 3,3-dimethyl substituent on the rate of intramolecular cyclization between N-terminal amine and 5-position amide bond in different buffer solutions was also evaluated.
- Hsu, Tsu,Tsai, Ting-Yueh,Tseng, Ya-Ju,Chiou, Mei-Chun,Lu, Cheng-Tai,Chao, Yu-Sheng,Jiaang, Weir-Torn
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scheme or table
p. 108 - 117
(2011/11/12)
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- Process for the preparation of sitagliptin
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A process for the preparation of 2(R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]-7(8H)-pyrazinyl]-1-(2,4,5-trifluorophenyl)-2-butanamine and intermediates useful for the synthesis thereof.
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Page/Page column 9-10
(2011/01/12)
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- FUSED TRIAZOLE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to novel fused triazole derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DPP-IV inhibitors") and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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Page/Page column 47
(2008/06/13)
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- First generation process for the preparation of the DPP-IV inhibitor sitagliptin
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A new synthesis of sitagliptin (MK-0431), a DPP-IV inhibitor and potential new treatment for type II diabetes, suitable for the preparation of multi-kilogram quantities is presented. The triazolopyrazine fragment of sitagliptin was prepared in 26% yield over four chemical steps using a synthetic strategy similar to the medicinal chemistry synthesis. Key process developments were made in the first step of this sequence, the addition of hydrazine to chloropyrazine, to ensure its safe operation on a large scale. The beta-amino acid fragment of sitagliptin was prepared by asymmetric reduction of the corresponding beta-ketoester followed by a two-step elaboration to an N-benzyloxy beta-lactam. Hydrolysis of the lactam followed by direct coupling to the triazolopiperazine afforded sitagliptin after cleavage of the N-benzyloxy group and salt formation. The overall yield was 52% over eight steps.
- Hansen, Karl B.,Balsells, Jaume,Dreher, Spencer,Hsiao, Yi,Kubryk, Michele,Palucki, Michael,Rivera, Nelo,Steinhuebel, Dietrich,Armstrong III, Joseph D.,Askin, David,Grabowski, Edward J. J.
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p. 634 - 639
(2012/12/25)
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- (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a] pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: A potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
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A novel series of β-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H) -yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (1) is a potent, orally active DPP-IV inhibitor (IC50 = 18 nM) with excellent selectivity over other proline-selective peptidases, oral bioavailability in preclinical species, and in vivo efficacy in animal models. MK-0431, the phosphate salt of compound 1, was selected for development as a potential new treatment for type 2 diabetes.
- Kim, Dooseop,Wang, Liping,Beconi, Maria,Eiermann, George J.,Fisher, Michael H.,He, Huaibing,Hickey, Gerard J.,Kowalchick, Jennifer E.,Leiting, Barbara,Lyons, Kathryn,Marsilio, Frank,McCann, Margaret E.,Patel, Reshma A.,Petrov, Aleksandr,Scapin, Giovanna,Patel, Sangita B.,Roy, Ranabir Sinha,Wu, Joseph K.,Wyvratt, Matthew J.,Zhang, Bei B.,Zhu, Lan,Thornberry, Nancy A.,Weber, Ann E.
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p. 141 - 151
(2007/10/03)
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- 3-AMINO-4-PHENYLBUTANOIC ACID DERIVATIVES AS DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to 3-amino-4-phenylbutanoic acid derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DP-IV inhibitors") and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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Page/Page column 87
(2010/02/07)
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