- Preparation method of glutaryl imide derivative
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The invention discloses a preparation method of a glutaryl imide derivative, which comprises the following steps: in a negative pressure state, dropwise adding acetic anhydride into molten 1, 1-cyclohexyl diacetic acid, and reacting to obtain 1, 1-cyclohexyl diacetic anhydride; adding ammonia water into an ammoniation kettle, dropwise adding 1, 1-cyclohexanediacetic anhydride to carry out ammoniation reaction, and adding hydrochloric acid to adjust the pH value, so as to obtain precipitated crystals, namely pentane valeric acid; adding pentane valeric acid, a toluene solvent and glacial aceticacid into the reaction kettle, heating, stirring, reacting, cooling, and carrying out suction filtration to obtain a filter cake; and adding the filter cake into ammonia water for soaking and stirring, carrying out suction filtration again, leaching with deionized water, and drying to obtain glutaryl imide. According to the preparation method of a glutaryl imide derivative, acetic anhydride and 1, 1-cyclohexyldiacetic acid are used as raw materials, so that the reaction efficiency is effectively improved, the product yield is increased, the production cost of the product is reduced, and producing benefits are improved.
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Paragraph 0037-0038; 0044-0045; 0051-0052
(2021/03/31)
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- Preparation method and application of 1-1 - cyclohexane - diacetic acid monoamide
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The invention discloses a preparation method of 1-1 - cyclohexane - diacetic acid monoamide (CDMA), which comprises an amidation reaction of 1, 1 - cyclohexanedicarboxylic acid anhydride and 1 and 1 - cyclohexane - diacetic acid monoamide ammonium salt in a non-polar solvent of non-benzene to obtain 1, 1 - cyclohexane - diacetic acid monoamide (CDMA). Alternatively, in the non-polar solvent of non-benzene, 1, 1 - cyclohexanedicarboxylic anhydride is reacted with ammonia to heat reflux to give 3, 3 - cyclopentanediimides. 3,3 - Cycloglutarimide is obtained 1 by untying a base water, 1 - cyclohexane - diacetic acid monoamide (CDMA) wherein, with 1, 1 - cyclohexanedicarboxylic acid as a starting material, dehydration is carried out under acid catalysis to give 1, 1 - cyclohexanedicarboxylic acid anhydride.
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Paragraph 0094-0139
(2021/09/29)
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- VITRIFIED STATE STABILIZING AGENT FOR ANIMAL CELL CRYOPRESERVATION SOLUTION
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Provided are a vitrification stabilizer for animal cell cryopreservation fluid, and an animal cell cryopreservation fluid that exhibits superior vitrification capacity due to containing said vitrification stabilizer for animal cell cryopreservation fluid. The vitrification stabilizer for animal cell cryopreservation fluid contains an amphoteric polymer compound selected from the group consisting of: (a) an amphoteric polymer compound obtained by reacting ?-poly-L-lysine with butyl succinic acid anhydride and performing carboxylation; (b) an amphoteric polymer compound obtained by reacting ?-poly-L-lysine with butyl succinic acid anhydride and succinic acid anhydride, and performing carboxylation; and (c) an amphoteric polymer compound obtained by reacting ?-poly-L-lysine with a compound represented by formula (I) and performing carboxylation.
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- A process for synthesis of gabapentin
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The invention discloses a gabapentin synthesis technology. The gabapentin synthesis technology comprises the following steps of 1, preparing 1,1-cyclohexane diacetic anhydride, 2, preparing 3,3-cyclopentaneglutaramic acid, 3, preparing gabapentin hydrochloride, 4, adding the gabapentin hydrochloride into an oxalic acid solution, adjusting a pH value to 2-5, carrying out stirring, carrying out pressure reduction condensation to obtain filter cake, dissolving the filter cake in ethanol, carrying out stirring for dissolution, and carrying out pressure reduction drying to obtain fined gabapentin oxalate, and 5, adding the fined gabapentin oxalate into absolute ethanol, adjusting a PH value to 7-8, carrying out stirring, adding active carbon into the mixture, carrying out heating reflux, carrying out filtration, carrying out pressure reduction drying to obtain a gabapentin hydrate, adding the gabapentin hydrate into absolute ethanol, carrying out heating dissolution, carrying out cooling, carrying out filtration, concentrating the filtrate, carrying out cooling for crystal precipitation, carrying out filtration, carrying out washing by absolute ethanol and carrying out drying to obtain gabapentin. Gabapentin obtained by the gabapentin synthesis technology has high content and a high yield.
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Paragraph 0032
(2016/11/24)
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- Synthesis of oxytocin analogues with replacement of sulfur by carbon gives potent antagonists with increased stability
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The neuropeptide oxytocin 1 controls mammary and uterine smooth muscle contraction. Atosiban 2, an oxytocin antagonist, is used for prevention of preterm labor and premature birth. However, the metabolic lifetimes of such peptide drugs are short because of in vivo degradation. Facile production of oxytocin analogues with varying ring sizes wherein sulfur is replaced by carbon (methylene or methine) could be achieved by standard solid-phase peptide synthesis using olefin-bearing amino acids followed by on-resin ring-closing metathesis (RCM). These were tested for agonistic and antagonistic uteronic activity using myometrial strips taken from nonpregnant female rats. Peptide 8 showed agonistic activity in vitro (EC50 = 1.4 × 103 ± 4.4 102 nM) as compared to 1 (EC50 = 7.0 ± 2.1 nM). Atosiban analogues 17 (pA2 = 7.8 ± 0.1) and 18 (pA2 = 8.0 ± 0.1) showed substantial activity compared to the parent oxytocin antagonist 2 (pA2 = 9.9 ± 0.3). Carba analogue 35 (pA2 = 6.1 ± 0.1) had an agonistic activity over 2 orders of magnitude less than its parent 3 (8.8 ± 0.5). A comparison of biological stabilities of 1,6-carba analogues of both an agonist 8 and antagonist 18 versus parent peptides 1 and 2 was conducted. The half-lives of peptides 8 and 18 in rat placental tissue were shown (Table 2) to be greatly improved versus their parents oxytocin 1 and atosiban 2, respectively. These results suggest that peptides 8 and 18 and analogues thereof may be important leads into the development of a long-lasting, commercially available therapeutic for initiation of parturition and treatment of preterm labor.
- Stymiest, Jake L.,Mitchell, Bryan F.,Wong, Susan,Vederas, John C.
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p. 7799 - 7809
(2007/10/03)
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- PROCESS FOR THE PREPARATION OF GABAPENTIN
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The present invention relates to an improved process for the preparation of gabapentin and, more particularly, to an improvement of the preparation reaction of 1,1-cyclohexanediacetic acid monoamide, intermediate utilized in the preparation of gabapentin.
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Page/Page column 6-7
(2008/06/13)
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- NOVEL 4-(2FUROYL)AMINOPIPERIDINES, INTERMEDIATES IN SYNTHESIZING THE SAME,PROCESS FOR PRODUCING THE SAME AND MEDICINAL USE OF THE SAME
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There are provided novel 4-(2-furoyl)aminopiperidines represented by the general formula (I), their synthetic intermediates, processes for their preparation and medicaments containing them. In the above formula, X is CH or N, and Y is a group of the following general formula (II), formula (II-a) or formula (III): wherein a, b and c are each an integer of 0-6; Z is CH2 or NH; W is O or S; T is O or N-R15 wherein R15 is H, a C1-C6 alkyl group, a benzyl group or a phenethyl group; and R1 is H, a C1-C6 alkoxycarbonyl group, a benzyloxycarbonyl group, or the like.The 4-(2-furoyl) aminopiperidine derivatives according to this invention possess opioid μ antagonistic activity and are useful for the treatment or prevention of side effects which are caused by μ receptors agonist and which are selected from constipation, nausea/emesis or itch, or for the treatment or prevention of idiopathic constipation, postoperative ileus, paralytic ileus, irritable bowel syndrome or chronic pruritus.
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- SUBSTITUTED CYCLOALKANECARBOXYLIC ACID DERIVATIVES AS MATRIX METALLOPROTEASE INHIBITORS
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Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula STR1 wherein each T is a substituent g roup; x is 0, 1, or 2; the group D represents STR2 the subscript "e" is 2 or 3; the group R 14 represents a variety of possible substituent groups of the cycloalkyl ring between D and G; the subscript "k" is 0-2; and the group G represents M, STR3 in which M represents--CO 2 H,--CON(R 11) 2, or--CO 2 R 12 ; and R 13 represents any of the side chains of the 19 noncyclic occurring amino acids. "
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- Antiarthritic and suppressor cell inducing activity of azaspiranes: Structure-function relationships of a novel class of immunomodulatory agents
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Spirogermanium (1;8,8-diethyl-N,N-dimethyl-2-aza-8-germaspiro[4.5]decane-2-propanamin e dihydrochloride) is a potent cytotoxic agent in vitro which has demonstrated limited activity in experimental animal tumor models. Subsequently, it has been reported that spirogermanium has antiarthritic and suppressor cell-inducing activity. We have synthesized a series of substituted 8-hetero-2-azaspiro[4.5]decane and 9-hetero-3-azaspiro[5.5]undecane analogues of spirogermanium to identify the heteroatom requirements for in vivo antiarthritic and suppressor cell-inducing activity. This structure-activity relationship study has identified that appropriately substituted silicon and carbon analogues of spirogermanium retain both antiarthritic and immunosuppressive activity, with the 8,8-dipropyl (carbon) analogue being among the most active. Following the identification of N,N-dimethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2-propanamine dihydrochloride (9) as more active analogue than spirogermanium, a series of 8,8-dipropyl analogues with various amine substituents were synthesized. A number of these analogues had activity similar to that of 9. A correlation between activity in the adjuvant arthritic rat and the ability to induce suppressor cells (r = 0.894, p0.001) suggests an association between the two pharmacologic effects. While the precise biochemical mechanism(s) for the pharmacological activity is unclear, these data suggest that compounds within this series, e.g., N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine dihydrochloride, may provide effective therapy in diseases of autoimmune origin and/or the prevention of rejection in tissue transplantation.
- Badger,Schwartz,Picker,Dorman,Bradley,Cheeseman,DiMartino,Hanna,Mirabelli
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p. 2963 - 2970
(2007/10/02)
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- Synthesis of 6,6-Pentamethylene-2-aminosuberic Acid. A Key Intermediate in the Synthesis of Dicarba Analogues of Vasopressin Antagonists
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Two complementary syntheses of the unnatural amino acid, 6,6-cyclopentamethylene-2-aminosuberic acid, Pas (2) are described.The first, starting from methyl cyclohexanecarboxylate (4), yields in ten steps racemic Boc-Pas(OBzl)-OH (3) which is suitably protected for solid phase peptide synthesis.The second method involves the stereospecific synthesis of optically pure Boc-Pas(OBzl)-OH (3L) utilizing the electrochemical coupling, via the Kolbe method of the monobenzyl ester of 1,1-cyclohexanediacetic acid (13) and Boc-L-Glu-OBzl (14).The optical purity of 3L was confirmed by chiral gas chromatographic analysis of its N-pentafluoropropionyl diisopropyl ester derivative 15L.
- Callahan, James F.,Newlander, Kenneth A.,Bryan, Heidemarie G.,Huffman, William F.,Moore, Michael L.,Yim, Nelson C. F.
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p. 1527 - 1530
(2007/10/02)
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